GALACTIC-HF: Registrational Study With Omecamtiv Mecarbil (AMG 423) to Treat Chronic Heart Failure With Reduced Ejection Fraction

• Sponsor: Cytokinetics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02929329
• Collaborator: (none)
• Enrollment: 8,256
• Locations: 1034
• Arms: 2
• Actual Duration (Months): 44.3
• Patients Per Site: 8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if treatment with omecamtiv mecarbil when added to standard of care is well tolerated and superior to placebo in reducing the risk of cardiovascular death or heart failure events in adults with chronic heart failure with reduced ejection fraction (HFrEF).

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Drug: Omecamtiv Mecarbil; Drug: Placebo; Drug: Standard of Care	Phase 3

Detailed Description

This study was conducted by Amgen as the IND holder, with Cytokinetics as a collaborator. Due to the termination of the collaboration agreement between Amgen and Cytokinetics in May 2021 and subsequent transfer of the omecamtiv mecarbil IND from Amgen to Cytokinetics, Cytokinetics is now listed as the sponsor.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8256 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of Omecamtiv Mecarbil on Mortality and Morbidity in Subjects With Chronic Heart Failure With Reduced Ejection Fraction (GALACTIC-HF)
• Actual Study Start Date: Jan 6, 2017
• Actual Primary Completion Date: Sep 14, 2020
• Actual Study Completion Date: Sep 14, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Omecamtiv Mecarbil Participants received oral omecamtiv mecarbil (OM) twice daily in addition to standard heart failure therapy. The starting dose of OM was 25 mg; At week 4, participants with week 2 OM predose plasma concentrations < 200 ng/mL had their dose increased to 50 mg BID; participants with week 2 predose plasma concentrations ≥ 200 and < 300 ng/mL had their dose increased to 37.5 mg BID and participants with week 2 predose plasma concentrations ≥ 300 ng/mL and < 1000 ng/mL maintained a 25 mg BID dosing regimen.	Drug: Omecamtiv Mecarbil; Omecamtiv mecarbil tablets for oral administration; Other Names: AMG 423 ; Drug: Standard of Care; Participants were required to be optimally managed with standard of care therapies for chronic HF (eg, beta blockers, renin angiotensin aldosterone system inhibitors), consistent with regional clinical practice guidelines, unless contraindicated.
Placebo Comparator: Placebo Participants received matching placebo tablets twice a day in addition to standard heart failure therapy.	Drug: Placebo; Matching placebo tablets; Drug: Standard of Care; Participants were required to be optimally managed with standard of care therapies for chronic HF (eg, beta blockers, renin angiotensin aldosterone system inhibitors), consistent with regional clinical practice guidelines, unless contraindicated.

Outcome Measures

Primary Outcome Measures

1. Time to Cardiovascular Death or First Heart Failure Event [From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.]

   The primary outcome was a composite of a heart-failure (HF) event or cardiovascular (CV) death, whichever occurred first, in a time-to-event analysis. A heart-failure event was defined as an urgent clinic visit, emergency department visit, or hospitalization for subjectively and objectively worsening heart failure leading to treatment intensification beyond a change in oral diuretic therapy. All deaths and HF events were adjudicated by an independent external clinical events committee (CEC) at the Duke Clinical Research Institute, using standardized definitions based on the recent American College of Cardiology/American Heart Association (ACC/AHA) standards for endpoint definitions in cardiovascular clinical trials. Time to cardiovascular death or first HF event was analyzed using Kaplan-Meier (KM) methods. Since the median was not calculated, the percentage of participants with a positively adjudicated event during the study is reported.

Secondary Outcome Measures

1. Time to Cardiovascular Death [From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.]

   Cardiovascular death includes acute myocardial infarction (MI), sudden cardiac death, death due to heart failure, death due to stroke, death due to cardiovascular (CV) procedures, death due to CV hemorrhage, and death due to other CV causes. All deaths were adjudicated by an independent external clinical-events committee at the Duke Clinical Research Institute, using standardized definitions based on the recent ACC/AHA standards for endpoint definitions in cardiovascular clinical trials. Time to cardiovascular death was analyzed using Kaplan-Meier methods. Since the median was not calculated, the percentage of participants with a positively adjudicated event during the study is reported.

2. Change From Baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ TSS) at Week 24 [Baseline and Week 24]

   The Kansas City Cardiomyopathy Questionnaire is a self-administered questionnaire with a 2-week recall period that includes 23 items that map to 7 domains: symptom frequency; symptom burden; symptom stability; physical limitations; social limitations; quality of life; and self-efficacy (the patient's understanding of how to manage their heart failure). The symptom frequency and symptom burden domains are merged into a total symptom score. Scores are represented on a 0-to-100-point scale, where lower scores represent more frequent and severe symptoms and scores of 100 indicate no symptoms. The change from baseline in KCCQ TSS was analyzed separately for each randomization setting (inpatient and outpatient). Least squares means are from the mixed model which includes baseline total symptom score value, region, baseline eGFR, scheduled visit, treatment group and interaction of treatment with scheduled visit as covariates.

3. Time to First Heart Failure Hospitalization [From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.]

   A HF hospitalization is defined as an event that met all of the following criteria: The participant was admitted to the hospital with a primary diagnosis of HF; The length of stay in the hospital extended for at least 24 hours; The participant exhibited documented new or worsening symptoms due to HF on presentation; The participant had objective evidence of new or worsening HF; The participant received initiation or intensification of treatment specifically for HF, including an intravenous diuretic or vasoactive agent, mechanical or surgical intervention, or mechanical fluid removal. Events were adjudicated by an independent external CEC at the Duke Clinical Research Institute using standardized definitions based on the ACC/AHA standards for endpoint definitions in CV clinical trials. Time to first HF hospitalization was analyzed using KM methods. Since the median was not calculated, the percentage of participants with a positively adjudicated event is reported.

4. Time to All-cause Death [From randomization up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.]

   All events were adjudicated by an independent external clinical-events committee at the Duke Clinical Research Institute, using standardized definitions based on the recent ACC/AHA standards for endpoint definitions in cardiovascular clinical trials. Time to all-cause death was analyzed using Kaplan-Meier methods. Since the median was not calculated, the percentage of participants with an event are reported. Events that occurred up to the earliest of last confirmed survival status date or analysis cut-off date (07 August 2020) are included.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Subject has provided informed consent

• Male or female, ≥ 18 to ≤ 85 years

• History of chronic heart failure (HF), defined as requiring treatment for HF for a minimum of 30 days before randomization

• Left ventricle ejection fraction (LVEF) ≤ 35%, per subjects most recent medical record, within 12 months prior to screening.

• New York Heart Association (NYHA) class II to IV at most recent screening assessment.

• Managed with HF standard of care (SoC) therapies consistent with regional clinical practice guidelines according to investigator judgment of subject's clinical status

• Current hospitalization with primary reason of HF OR one of the following events within 1 year of screening: hospitalization with primary reason of HF; urgent visit to emergency department (ED) with primary reason of HF.

• Elevated B-type natriuretic peptide (BNP) or n-terminal-prohormone brain natriuretic peptide (NT-proBNP)

Other Inclusion Criteria May apply

Key Exclusion Criteria:

• Currently receiving treatment in another investigational device or drug study, or < 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.

• Malignancy within 5 years prior to randomization with the following exceptions: localized basal or squamous cell carcinoma of the skin, cervical intraepithelial neoplasia, stage 1 prostate carcinoma, breast ductal carcinoma in situ.

• Subject has known sensitivity to any of the products or components to be administered during testing

Other Exclusion Criteria May apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35233
2	Research Site	Birmingham	Alabama	United States	35243
3	Research Site	Birmingham	Alabama	United States	35294
4	Research Site	Fort Payne	Alabama	United States	35967
5	Research Site	Huntsville	Alabama	United States	35801
6	Research Site	Mobile	Alabama	United States	36608
7	Research Site	Scottsboro	Alabama	United States	35768
8	Research Site	Tuscumbia	Alabama	United States	35674
9	Research Site	Gilbert	Arizona	United States	85297
10	Research Site	Phoenix	Arizona	United States	85032
11	Research Site	Tucson	Arizona	United States	85710
12	Research Site	Tucson	Arizona	United States	85724
13	Research Site	Jonesboro	Arkansas	United States	72401
14	Research Site	Little Rock	Arkansas	United States	72205
15	Research Site	Anaheim	California	United States	92801
16	Research Site	Beverly Hills	California	United States	90211
17	Research Site	Burbank	California	United States	91505
18	Research Site	Carmichael	California	United States	95608
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20	Research Site	Huntington Beach	California	United States	92648
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22	Research Site	Long Beach	California	United States	90806
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154	Research Site	Columbia	Missouri	United States	65212
155	Research Site	Jefferson City	Missouri	United States	65109
156	Research Site	Kansas City	Missouri	United States	64108
157	Research Site	Kansas City	Missouri	United States	64128
158	Research Site	Saint Louis	Missouri	United States	63110
159	Research Site	Springfield	Missouri	United States	65807
160	Research Site	Lincoln	Nebraska	United States	68506
161	Research Site	Omaha	Nebraska	United States	68198
162	Research Site	Las Vegas	Nevada	United States	89118
163	Research Site	Las Vegas	Nevada	United States	89128
164	Research Site	North Las Vegas	Nevada	United States	89086
165	Research Site	Reno	Nevada	United States	89502
166	Research Site	Lebanon	New Hampshire	United States	03756
167	Research Site	Eatontown	New Jersey	United States	07724
168	Research Site	Moorestown	New Jersey	United States	08057
169	Research Site	Morristown	New Jersey	United States	07960
170	Research Site	Newark	New Jersey	United States	07112
171	Research Site	Ridgewood	New Jersey	United States	07450
172	Research Site	Somerset	New Jersey	United States	08873
173	Research Site	Voorhees	New Jersey	United States	08043
174	Research Site	Albuquerque	New Mexico	United States	87106
175	Research Site	Albany	New York	United States	12208
176	Research Site	Bronx	New York	United States	10467
177	Research Site	Brooklyn	New York	United States	11215
178	Research Site	Buffalo	New York	United States	14215
179	Research Site	Cortlandt Manor	New York	United States	10567
180	Research Site	Johnson City	New York	United States	13790
181	Research Site	Kingston	New York	United States	12401
182	Research Site	Laurelton	New York	United States	11413
183	Research Site	Mineola	New York	United States	11501
184	Research Site	New York	New York	United States	10016
185	Research Site	New York	New York	United States	10025
186	Research Site	New York	New York	United States	10029
187	Research Site	Rochester	New York	United States	14621
188	Research Site	Roslyn	New York	United States	11576
189	Research Site	Saratoga Springs	New York	United States	12866
190	Research Site	Stony Brook	New York	United States	11794
191	Research Site	Valhalla	New York	United States	10595
192	Research Site	Asheville	North Carolina	United States	28803
193	Research Site	Cary	North Carolina	United States	27518
194	Research Site	Chapel Hill	North Carolina	United States	27599
195	Research Site	Charlotte	North Carolina	United States	28203
196	Research Site	Durham	North Carolina	United States	27705
197	Research Site	Greensboro	North Carolina	United States	27401
198	Research Site	Hickory	North Carolina	United States	28601
199	Research Site	Lenoir	North Carolina	United States	28645
200	Research Site	Lumberton	North Carolina	United States	28358
201	Research Site	Mooresville	North Carolina	United States	28117
202	Research Site	Pinehurst	North Carolina	United States	28374
203	Research Site	Tabor City	North Carolina	United States	28463
204	Research Site	Wilmington	North Carolina	United States	28401
205	Research Site	Winston-Salem	North Carolina	United States	27103
206	Research Site	Cincinnati	Ohio	United States	45219
207	Research Site	Cincinnati	Ohio	United States	45220
208	Research Site	Cincinnati	Ohio	United States	45267
209	Research Site	Cleveland	Ohio	United States	44106
210	Research Site	Cleveland	Ohio	United States	44195
211	Research Site	Columbus	Ohio	United States	43210
212	Research Site	Columbus	Ohio	United States	43214
213	Research Site	Dayton	Ohio	United States	45414
214	Research Site	Dayton	Ohio	United States	45419
215	Research Site	Kettering	Ohio	United States	45429
216	Research Site	Marion	Ohio	United States	43302
217	Research Site	Sandusky	Ohio	United States	44870
218	Research Site	Wiloughby	Ohio	United States	44094
219	Research Site	Oklahoma City	Oklahoma	United States	73135
220	Research Site	Tulsa	Oklahoma	United States	74104
221	Research Site	Tulsa	Oklahoma	United States	74127
222	Research Site	Abington	Pennsylvania	United States	19001
223	Research Site	Altoona	Pennsylvania	United States	16602
224	Research Site	Butler	Pennsylvania	United States	16001
225	Research Site	Camp Hill	Pennsylvania	United States	17011
226	Research Site	Erie	Pennsylvania	United States	16502
227	Research Site	Hershey	Pennsylvania	United States	17033
228	Research Site	Jersey Shore	Pennsylvania	United States	17740
229	Research Site	Lancaster	Pennsylvania	United States	17603
230	Research Site	Philadelphia	Pennsylvania	United States	19102
231	Research Site	Philadelphia	Pennsylvania	United States	19107
232	Research Site	Philadelphia	Pennsylvania	United States	19114
233	Research Site	Philadelphia	Pennsylvania	United States	19141
234	Research Site	Pittsburgh	Pennsylvania	United States	15212
235	Research Site	Pittsburgh	Pennsylvania	United States	15213
236	Research Site	Sayre	Pennsylvania	United States	18840
237	Research Site	Yardley	Pennsylvania	United States	19067
238	Research Site	York	Pennsylvania	United States	17403
239	Research Site	Pawtucket	Rhode Island	United States	02860
240	Research Site	Providence	Rhode Island	United States	02906
241	Research Site	Providence	Rhode Island	United States	02908
242	Research Site	Warwick	Rhode Island	United States	02886
243	Research Site	Charleston	South Carolina	United States	29401
244	Research Site	Charleston	South Carolina	United States	29407
245	Research Site	Charleston	South Carolina	United States	29425
246	Research Site	Fort Mill	South Carolina	United States	29707
247	Research Site	Greenville	South Carolina	United States	29605
248	Research Site	Rock Hill	South Carolina	United States	29732
249	Research Site	Rapid City	South Dakota	United States	57701
250	Research Site	Germantown	Tennessee	United States	38138
251	Research Site	Jackson	Tennessee	United States	38301
252	Research Site	Jackson	Tennessee	United States	38305
253	Research Site	Knoxville	Tennessee	United States	37934
254	Research Site	Memphis	Tennessee	United States	38104
255	Research Site	Nashville	Tennessee	United States	37208
256	Research Site	Nashville	Tennessee	United States	37212
257	Research Site	Nashville	Tennessee	United States	37232
258	Research Site	Oak Ridge	Tennessee	United States	37830
259	Research Site	Powell	Tennessee	United States	37849
260	Research Site	Tullahoma	Tennessee	United States	37388
261	Research Site	Amarillo	Texas	United States	79106
262	Research Site	Carrollton	Texas	United States	75006
263	Research Site	Carrollton	Texas	United States	75010
264	Research Site	Dallas	Texas	United States	75216
265	Research Site	Dallas	Texas	United States	75231
266	Research Site	Dallas	Texas	United States	75246
267	Research Site	Denison	Texas	United States	75020
268	Research Site	El Paso	Texas	United States	79935
269	Research Site	Fort Sam Houston	Texas	United States	78234
270	Research Site	Fort Worth	Texas	United States	76104
271	Research Site	Galveston	Texas	United States	77555-0158
272	Research Site	Gonzales	Texas	United States	78629
273	Research Site	Houston	Texas	United States	77025
274	Research Site	Houston	Texas	United States	77030
275	Research Site	Huntsville	Texas	United States	77340
276	Research Site	Lubbock	Texas	United States	79430
277	Research Site	McKinney	Texas	United States	75071
278	Research Site	Odessa	Texas	United States	79761
279	Research Site	Plano	Texas	United States	75024
280	Research Site	San Antonio	Texas	United States	78229
281	Research Site	Tomball	Texas	United States	77375
282	Research Site	Wichita Falls	Texas	United States	76301
283	Research Site	Farmington	Utah	United States	84025
284	Research Site	Murray	Utah	United States	84107
285	Research Site	Salt Lake City	Utah	United States	84132
286	Research Site	Burlington	Vermont	United States	05401
287	Research Site	White River Junction	Vermont	United States	05009
288	Research Site	Charlottesville	Virginia	United States	22908
289	Research Site	Leesburg	Virginia	United States	20176
290	Research Site	Lynchburg	Virginia	United States	24501
291	Research Site	Manassas	Virginia	United States	20109
292	Research Site	Norfolk	Virginia	United States	23510
293	Research Site	Richmond	Virginia	United States	23226
294	Research Site	Richmond	Virginia	United States	23249
295	Research Site	Richmond	Virginia	United States	23298
296	Research Site	Virginia Beach	Virginia	United States	23454
297	Research Site	Puyallup	Washington	United States	98372
298	Research Site	Seattle	Washington	United States	98122
299	Research Site	Spokane	Washington	United States	99204
300	Research Site	Huntington	West Virginia	United States	25702
301	Research Site	Morgantown	West Virginia	United States	26506
302	Research Site	Green Bay	Wisconsin	United States	54301
303	Research Site	Madison	Wisconsin	United States	53705
304	Research Site	Madison	Wisconsin	United States	53713
305	Research Site	Madison	Wisconsin	United States	53792
306	Research Site	Manitowoc	Wisconsin	United States	54220
307	Research Site	Milwaukee	Wisconsin	United States	53201
308	Research Site	Milwaukee	Wisconsin	United States	53226
309	Research Site	Milwaukee	Wisconsin	United States	53295
310	Research Site	Waukesha	Wisconsin	United States	53188
311	Research Site	Bahia Blanca	Buenos Aires	Argentina	B8000FTD
312	Research Site	Caba	Buenos Aires	Argentina	C1119ACN
313	Research Site	Caba	Buenos Aires	Argentina	C1406BOA
314	Research Site	Caba	Buenos Aires	Argentina	C1407GTN
315	Research Site	Caba	Buenos Aires	Argentina	C1428ART
316	Research Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	1209
317	Research Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1280AEB
318	Research Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1426ABP
319	Research Site	Coronel Suarez	Buenos Aires	Argentina	B7540GHD
320	Research Site	Mar del Plata	Buenos Aires	Argentina	B7600FZN
321	Research Site	Merlo	Buenos Aires	Argentina	B1722COV
322	Research Site	Quilmes	Buenos Aires	Argentina	1878
323	Research Site	Quilmes	Buenos Aires	Argentina	B1878DVB
324	Research Site	Ramos Meija	Buenos Aires	Argentina	B1704ETD
325	Research Site	San Fernando	Buenos Aires	Argentina	B1646EBJ
326	Research Site	San Isidro	Buenos Aires	Argentina	B1642DSF
327	Research Site	San Martin	Buenos Aires	Argentina	B1650CSQ
328	Research Site	San Nicolas	Buenos Aires	Argentina	B2900DPA
329	Research Site	Cordoba	Córdoba	Argentina	5000
330	Research Site	Cordoba	Córdoba	Argentina	X5004BAL
331	Research Site	Cordoba	Córdoba	Argentina	X5006IKK
332	Research Site	Cordoba	Córdoba	Argentina	X5016KEH
333	Research Site	Villa Maria	Córdoba	Argentina	X5900JKA
334	Research Site	Santa Rosa	La Pampa	Argentina	6300
335	Research Site	Rosario	Santa Fe	Argentina	2000
336	Research Site	Rosario	Santa Fe	Argentina	S2000BIF
337	Research Site	Venado Tuerto	Santa Fe	Argentina	2600
338	Research Site	San Miguel de Tucuman	Tucuman	Argentina	4000
339	Research Site	San Miguel de Tucuman	Tucuman	Argentina	T4000JCV
340	Research Site	Buenos Aires		Argentina	1425
341	Research Site	Corrientes		Argentina	3400
342	Research Site	Corrientes		Argentina	W3400AMZ
343	Research Site	Córdoba		Argentina	5000
344	Research Site	Córdoba		Argentina	X5003DCE
345	Research Site	Córdoba		Argentina	X5021FPQ
346	Research Site	Salta		Argentina	A4406BPF
347	Research Site	Santa Fe		Argentina	S3000FWO
348	Research Site	Garran	Australian Capital Territory	Australia	2605
349	Research Site	Concord	New South Wales	Australia	2139
350	Research Site	Darlinghurst	New South Wales	Australia	2010
351	Research Site	Liverpool	New South Wales	Australia	2170
352	Research Site	New Lambton Heights	New South Wales	Australia	2305
353	Research Site	Chermside	Queensland	Australia	4032
354	Research Site	Herston	Queensland	Australia	4029
355	Research Site	Woolloongabba	Queensland	Australia	4102
356	Research Site	Ashford	South Australia	Australia	5035
357	Research Site	Bedford Park	South Australia	Australia	5042
358	Research Site	Fullarton	South Australia	Australia	5063
359	Research Site	Woodville South	South Australia	Australia	5011
360	Research Site	Bundoora	Victoria	Australia	3083
361	Research Site	Frankston	Victoria	Australia	3199
362	Research Site	Geelong	Victoria	Australia	3220
363	Research Site	Richmond	Victoria	Australia	3121
364	Research Site	Murdoch	Western Australia	Australia	6150
365	Research Site	Feldkirch		Austria	6807
366	Research Site	Graz		Austria	8036
367	Research Site	Innsbruck		Austria	6020
368	Research Site	Linz		Austria	4010
369	Research Site	Linz		Austria	4020
370	Research Site	Sankt Poelten		Austria	3100
371	Research Site	Villach		Austria	9500
372	Research Site	Wien		Austria	1090
373	Research Site	Wien		Austria	1160
374	Research Site	Aalst		Belgium	9300
375	Research Site	Genk		Belgium	3600
376	Research Site	Gent		Belgium	9000
377	Research Site	Leuven		Belgium	3000
378	Research Site	Liège		Belgium	4000
379	Research Site	Lodelinsart		Belgium	6042
380	Research Site	Roeselare		Belgium	8800
381	Research Site	Brasilia	Distrito Federal	Brazil	70673-900
382	Research Site	Goiania	Goiás	Brazil	74223-130
383	Research Site	Goiania	Goiás	Brazil	74605-020
384	Research Site	Belo Horizonte	Minas Gerais	Brazil	30150-240
385	Research Site	Belo Horizonte	Minas Gerais	Brazil	31110-580
386	Research Site	Uberlandia	Minas Gerais	Brazil	38411-186
387	Research Site	Curitiba	Paraná	Brazil	80045-170
388	Research Site	Curitiba	Paraná	Brazil	80230-130
389	Research Site	Curitiba	Paraná	Brazil	80730-150
390	Research Site	Londrina	Paraná	Brazil	86038-350
391	Research Site	Natal	Rio Grande Do Norte	Brazil	59020-035
392	Research Site	Canoas	Rio Grande Do Sul	Brazil	92425-900
393	Research Site	Passo Fundo	Rio Grande Do Sul	Brazil	99010-080
394	Research Site	Porto Alegre	Rio Grande Do Sul	Brazil	90020-090
395	Research Site	Porto Alegre	Rio Grande Do Sul	Brazil	90035-903
396	Research Site	Porto Alegre	Rio Grande Do Sul	Brazil	90840-440
397	Research Site	Porto Alegre	Rio Grande Do Sul	Brazil	91350-200
398	Research Site	Aracaju	Sergipe	Brazil	49055-530
399	Research Site	Campinas	São Paulo	Brazil	13010-001
400	Research Site	Campinas	São Paulo	Brazil	13060-080
401	Research Site	Campinas	São Paulo	Brazil	13083-888
402	Research Site	Marilia	São Paulo	Brazil	17515-000
403	Research Site	Ribeirao Preto	São Paulo	Brazil	14048-900
404	Research Site	Sao Jose do Rio Preto	São Paulo	Brazil	15015-770
405	Research Site	Sao Paulo	São Paulo	Brazil	01317 002
406	Research Site	Sao Paulo	São Paulo	Brazil	04005-000
407	Research Site	Sao Paulo	São Paulo	Brazil	08270-120
408	Research Site	São José do Rio Preto	São Paulo	Brazil	15090-000
409	Research Site	Rio De Janeiro		Brazil	22271-100
410	Research Site	São Paulo		Brazil	04012-909
411	Research Site	São Paulo		Brazil	05403-000
412	Research Site	Haskovo		Bulgaria	6300
413	Research Site	Pleven		Bulgaria	5800
414	Research Site	Sandanski		Bulgaria	2800
415	Research Site	Sofia		Bulgaria	1202
416	Research Site	Sofia		Bulgaria	1233
417	Research Site	Sofia		Bulgaria	1407
418	Research Site	Sofia		Bulgaria	1527
419	Research Site	Sofia		Bulgaria	1750
420	Research Site	Edmonton	Alberta	Canada	T6G 2B7
421	Research Site	Edmonton	Alberta	Canada	T6K 4C1
422	Research Site	Kelowna	British Columbia	Canada	V1Y 1V6
423	Research Site	New Westminster	British Columbia	Canada	V3L 3W4
424	Research Site	North Vancouver	British Columbia	Canada	V7M 2H4
425	Research Site	Winnipeg	Manitoba	Canada	R2H 2A6
426	Research Site	Moncton	New Brunswick	Canada	E1G 1A7
427	Research Site	St. Johns	Newfoundland and Labrador	Canada	A1B 3V6
428	Research Site	Halifax	Nova Scotia	Canada	B3H 3A7
429	Research Site	Brampton	Ontario	Canada	L6W 2X7
430	Research Site	Brampton	Ontario	Canada	L6Z 4N5
431	Research Site	Cambridge	Ontario	Canada	N1R 6V6
432	Research Site	London	Ontario	Canada	N6A 5A5
433	Research Site	Oshawa	Ontario	Canada	L1J 2J9
434	Research Site	Ottawa	Ontario	Canada	K1Y 4W7
435	Research Site	Peterborough	Ontario	Canada	K9J 0B2
436	Research Site	Scarborough	Ontario	Canada	M1P 2V5
437	Research Site	Sudbury	Ontario	Canada	P3E 5M4
438	Research Site	Toronto	Ontario	Canada	M5B 1W8
439	Research Site	Waterloo	Ontario	Canada	N2T 0C1
440	Research Site	Chicoutimi	Quebec	Canada	G7H 7K9
441	Research Site	Greenfield Park	Quebec	Canada	J4V 2G8
442	Research Site	Laval	Quebec	Canada	H7M 3L9
443	Research Site	Montreal	Quebec	Canada	H1T 1C8
444	Research Site	Montreal	Quebec	Canada	H1T 3Y7
445	Research Site	Montreal	Quebec	Canada	H3G 1A4
446	Research Site	Montreal	Quebec	Canada	H4A 3J1
447	Research Site	Québec	Quebec	Canada	G1V 4G5
448	Research Site	St Jean sur Richelieu	Quebec	Canada	J3A 1J2
449	Research Site	St-Jérôme	Quebec	Canada	J7Z 5T3
450	Research Site	Terrebonne	Quebec	Canada	J6V 2H2
451	Research Site	Temuco	Cautín	Chile	4781156
452	Research Site	Temuco	Cautín	Chile	4813299
453	Research Site	Talcahuano	Concepción	Chile	4270918
454	Research Site	San Miguel	Santiago	Chile	8900085
455	Research Site	Vina del Mar	Valparaíso	Chile
456	Research Site	Osorno		Chile	5311092
457	Research Site	Santiago		Chile	7500739
458	Research Site	Santiago		Chile	8207257
459	Research Site	Santiago		Chile	8330034
460	Research Site	Santiago		Chile	8350595
461	Research Site	Santiago		Chile	8880300
462	Research Site	Santiago		Chile	8910259
463	Research Site	Santiago		Chile
464	Research Site	Beijing	Beijing	China	100043
465	Research Site	Beijing	Beijing	China	100191
466	Research Site	Guangzhou	Guangdong	China	510080
467	Research Site	Guangzhou	Guangdong	China	511400
468	Research Site	Haikou	Hainan	China	570102
469	Research Site	Harbin	Heilongjiang	China	150001
470	Research Site	Luoyang	Henan	China	471000
471	Research Site	Luoyang	Henan	China	471009
472	Research Site	Xinxiang	Henan	China	453000
473	Research Site	Zhengzhou	Henan	China	450052
474	Research Site	Hengyang	Hunan	China	421001
475	Research Site	Xiangtan	Hunan	China	411100
476	Research Site	Huhehaote	Inner Mongolia	China	010017
477	Research Site	Nanjing	Jiangsu	China	211100
478	Research Site	Suzhou	Jiangsu	China	215000
479	Research Site	Wuxi	Jiangsu	China	214023
480	Research Site	Xuzhou	Jiangsu	China	221006
481	Research Site	Changchun	Jilin	China	130021
482	Research Site	Changchun	Jilin	China	130033
483	Research Site	Shenyang	Liaoning	China	110000
484	Research Site	Shenyang	Liaoning	China	110004
485	Research Site	Shenyang	Liaoning	China	110016
486	Research Site	XI An	Shaanxi	China	710061
487	Research Site	Heze	Shandong	China	274031
488	Research Site	Jinan	Shandong	China	250012
489	Research Site	Jining	Shandong	China	272009
490	Research Site	QingDao	Shandong	China	266003
491	Research Site	Taiyuan	Shanxi	China	030001
492	Research Site	Taiyuan	Shanxi	China	030012
493	Research Site	Yuncheng	Shanxi	China	044000
494	Research Site	Tianjin	Tianjin	China	300052
495	Research Site	Urumqi	Xinjiang	China	830054
496	Research Site	Hangzhou	Zhejiang	China	310000
497	Research Site	Linhai	Zhejiang	China	317000
498	Research Site	Ningbo	Zhejiang	China	315010
499	Research Site	Beijing		China	100020
500	Research Site	Beijing		China	100037
501	Research Site	Shanghai		China	200080
502	Research Site	Medellin	Antioquia	Colombia	05001000
503	Research Site	Medellin	Antioquia	Colombia	050012
504	Research Site	Medellin	Antioquia	Colombia	050021
505	Research Site	Medellin	Antioquia	Colombia	050034
506	Research Site	Barranquilla	Atlántico	Colombia	080020
507	Research Site	Barranquilla	Atlántico	Colombia
508	Research Site	Cartagena	Bolívar	Colombia	130010
509	Research Site	Manizales	Caldas	Colombia
510	Research Site	Armenia	Quindío	Colombia	630004
511	Research Site	Bucaramanga	Santander	Colombia	680008
512	Research Site	Bucaramanga	Santander	Colombia	681004
513	Research Site	Cali	Valle Del Cauca	Colombia	760042
514	Research Site	Santiago de Cali	Valle Del Cauca	Colombia	760032
515	Research Site	Bogota D.C.		Colombia
516	Research Site	Beroun		Czechia	266 01
517	Research Site	Brandys nad Labem		Czechia	250 01
518	Research Site	Brno		Czechia	602 00
519	Research Site	Brno		Czechia	625 00
520	Research Site	Brno		Czechia	636 00
521	Research Site	Brno		Czechia	656 91
522	Research Site	Frydek Mistek		Czechia	738 01
523	Research Site	Havlickuv Brod		Czechia	580 22
524	Research Site	Hradec Kralove		Czechia	500 05
525	Research Site	Jihlava		Czechia	586 33
526	Research Site	Karlovy Vary		Czechia	360 01
527	Research Site	Kladno		Czechia	272 59
528	Research Site	Klatovy IV		Czechia	339 01
529	Research Site	Kolin III		Czechia	280 02
530	Research Site	Liberec		Czechia	460 63
531	Research Site	Louny		Czechia	440 01
532	Research Site	Marianske Lazne		Czechia	353 01
533	Research Site	Mohelnice		Czechia	789 85
534	Research Site	Opava		Czechia	746 01
535	Research Site	Ostrava		Czechia	728 80
536	Research Site	Policka		Czechia	572 01
537	Research Site	Praha 10		Czechia	100 34
538	Research Site	Praha 1		Czechia	110 00
539	Research Site	Praha 2		Czechia	128 08
540	Research Site	Praha 5 - Smichov		Czechia	150 00
541	Research Site	Pribram VIII		Czechia	261 01
542	Research Site	Svitavy		Czechia	568 25
543	Research Site	Teplice		Czechia	415 01
544	Research Site	Uherske Hradiste		Czechia	686 01
545	Research Site	Zlin		Czechia	762 75
546	Research Site	Znojmo		Czechia	669 02
547	Research Site	Aalborg		Denmark	9000
548	Research Site	Aarhus N		Denmark	8200
549	Research Site	Esbjerg		Denmark	6700
550	Research Site	Glostrup		Denmark	2600
551	Research Site	Hellerup		Denmark	2900
552	Research Site	Hillerod		Denmark	3400
553	Research Site	Køge		Denmark	4600
554	Research Site	Odense		Denmark	5000
555	Research Site	Svendborg		Denmark	5700
556	Research Site	Beziers cedex		France	34525
557	Research Site	Caen Cedex 9		France	14033
558	Research Site	Chambray les Tours		France	37170
559	Research Site	Corbeil Essonnes		France	91100
560	Research Site	Créteil Cedex		France	94010
561	Research Site	Dijon		France	21000
562	Research Site	Grenoble Cedex 9		France	38043
563	Research Site	Le Chesnay		France	78157
564	Research Site	Lille Cedex		France	59037
565	Research Site	Lille		France	59000
566	Research Site	Limoges Cedex		France	87042
567	Research Site	Lyon Cedex 03		France	69384
568	Research Site	Montauban		France	82017
569	Research Site	Montpellier cedex 05		France	34295
570	Research Site	Nantes Cedex 1		France	44093
571	Research Site	Nantes Cedex 2		France	44277
572	Research Site	Nimes cedex 9		France	30029
573	Research Site	Paris Cedex 13		France	75651
574	Research Site	Paris		France	75010
575	Research Site	Paris		France	75014
576	Research Site	Paris		France	75018
577	Research Site	Pessac Cedex		France	33604
578	Research Site	Poitiers		France	86000
579	Research Site	Rennes Cedex 9		France	35033
580	Research Site	Saint Denis		France	93200
581	Research Site	Toulon Cedex		France	83056
582	Research Site	Toulouse Cedex 9		France	31059
583	Research Site	Tourcoing cedex		France	59208
584	Research Site	Valenciennes		France	59300
585	Research Site	Bad Neuheim		Germany	61231
586	Research Site	Berlin		Germany	13353
587	Research Site	Dortmund		Germany	44137
588	Research Site	Düsseldorf		Germany	40225
589	Research Site	Erfurt		Germany	99089
590	Research Site	Erfurt		Germany	99097
591	Research Site	Essen		Germany	45147
592	Research Site	Frankfurt am Main		Germany	65929
593	Research Site	Freiburg		Germany	79106
594	Research Site	Greifswald		Germany	17475
595	Research Site	Göttingen		Germany	37075
596	Research Site	Haßloch		Germany	67454
597	Research Site	Heidelberg		Germany	69120
598	Research Site	Homburg		Germany	66421
599	Research Site	Köln		Germany	50937
600	Research Site	Langen		Germany	63225
601	Research Site	Leipzig		Germany	04289
602	Research Site	Ludwigshafen		Germany	67063
603	Research Site	Mainz		Germany	55131
604	Research Site	Markleeberg		Germany	04416
605	Research Site	Witten		Germany	58455
606	Research Site	Würzburg		Germany	97078
607	Research Site	Alexandroupoli		Greece	68100
608	Research Site	Athens		Greece	11527
609	Research Site	Athens		Greece	14233
610	Research Site	Athens		Greece	16673
611	Research Site	Chaidari, Athens		Greece	12462
612	Research Site	Chalkida		Greece	34100
613	Research Site	Heraklion		Greece	71110
614	Research Site	Ioannina		Greece	45500
615	Research Site	Larissa		Greece	41110
616	Research Site	Thessaloniki		Greece	54636
617	Research Site	Thessaloniki		Greece	56403
618	Research Site	Balatonfured		Hungary	8230
619	Research Site	Bekescsaba		Hungary	5600
620	Research Site	Berettyoujfalu		Hungary	4100
621	Research Site	Budapest		Hungary	1023
622	Research Site	Budapest		Hungary	1037
623	Research Site	Budapest		Hungary	1085
624	Research Site	Budapest		Hungary	1096
625	Research Site	Budapest		Hungary	1122
626	Research Site	Budapest		Hungary	1125
627	Research Site	Budapest		Hungary	1134
628	Research Site	Cegled		Hungary	2700
629	Research Site	Dunaujvaros		Hungary	2400
630	Research Site	Gyongyos		Hungary	3200
631	Research Site	Gyula		Hungary	5700
632	Research Site	Kaposvar		Hungary	7400
633	Research Site	Komarom		Hungary	2921
634	Research Site	Nyiregyhaza		Hungary	4400
635	Research Site	Pecs		Hungary	7624
636	Research Site	Sopron		Hungary	9400
637	Research Site	Szeged		Hungary	6725
638	Research Site	Szekszard		Hungary	7100
639	Research Site	Szentes		Hungary	6600
640	Research Site	Szolnok		Hungary	5004
641	Research Site	Zalaegerszeg		Hungary	8900
642	Research Site	Ariccia		Italy	00072
643	Research Site	Arzignano		Italy	36071
644	Research Site	Bergamo		Italy	24127
645	Research Site	Bologna		Italy	40139
646	Research Site	Brescia		Italy	25123
647	Research Site	Cagliari		Italy	09134
648	Research Site	Catania		Italy	95123
649	Research Site	Catanzaro		Italy	88100
650	Research Site	Cona FE		Italy	44124
651	Research Site	Cuneo		Italy	12100
652	Research Site	Foggia		Italy	71100
653	Research Site	Milano		Italy	20132
654	Research Site	Milano		Italy	20138
655	Research Site	Milano		Italy	20162
656	Research Site	Monza (MB)		Italy	20900
657	Research Site	Monza		Italy	20900
658	Research Site	Napoli		Italy	80131
659	Research Site	Palermo		Italy	90146
660	Research Site	Pavia		Italy	27100
661	Research Site	Perugia		Italy	06156
662	Research Site	Piacenza		Italy	29121
663	Research Site	Rimini		Italy	47923
664	Research Site	Roma		Italy	00163
665	Research Site	Rozzano MI		Italy	20089
666	Research Site	Seriate		Italy	24068
667	Research Site	Siena		Italy	53100
668	Research Site	Torrette Di Ancona		Italy	60126
669	Research Site	Trieste		Italy	34149
670	Research Site	Vimercate MB		Italy	20871
671	Research Site	Ichinomiya-shi	Aichi	Japan	491-8551
672	Research Site	Nagakute-shi	Aichi	Japan	480-1195
673	Research Site	Nagoya-shi	Aichi	Japan	454-8509
674	Research Site	Nagoya-shi	Aichi	Japan	466-8560
675	Research Site	Seto-shi	Aichi	Japan	489-8642
676	Research Site	Asahi-shi	Chiba	Japan	289-2511
677	Research Site	Chiba-shi	Chiba	Japan	260-8606
678	Research Site	Funabashi-shi	Chiba	Japan	273-8588
679	Research Site	Urayasu-shi	Chiba	Japan	279-0021
680	Research Site	Imabari-shi	Ehime	Japan	794-0006
681	Research Site	Matsuyama-shi	Ehime	Japan	790-0067
682	Research Site	Chikushino-shi	Fukuoka	Japan	818-8516
683	Research Site	Fukuoka-shi	Fukuoka	Japan	810-0001
684	Research Site	Fukuoka-shi	Fukuoka	Japan	810-8539
685	Research Site	Fukuoka-shi	Fukuoka	Japan	811-0213
686	Research Site	Fukuoka-shi	Fukuoka	Japan	812-0033
687	Research Site	Fukuoka-shi	Fukuoka	Japan	814-0180
688	Research Site	Fukuoka-shi	Fukuoka	Japan	815-8555
689	Research Site	Fukuoka-shi	Fukuoka	Japan	815-8588
690	Research Site	Kasuya-gun	Fukuoka	Japan	811-2316
691	Research Site	Kitakyushu-shi	Fukuoka	Japan	802-0077
692	Research Site	Kitakyushu-shi	Fukuoka	Japan	802-8555
693	Research Site	Kitakyushu-shi	Fukuoka	Japan	805-8508
694	Research Site	Koga-shi	Fukuoka	Japan	811-3195
695	Research Site	Kurume-shi	Fukuoka	Japan	830-8577
696	Research Site	Kurume-shi	Fukuoka	Japan	839-0863
697	Research Site	Onga-gun	Fukuoka	Japan	807-0051
698	Research Site	Fukushima-shi	Fukushima	Japan	960-1295
699	Research Site	Fukushima-shi	Fukushima	Japan	960-8251
700	Research Site	Fukushima-shi	Fukushima	Japan	960-8530
701	Research Site	Ogaki-shi	Gifu	Japan	503-8502
702	Research Site	Maebashi-shi	Gunma	Japan	371-8511
703	Research Site	Takasaki-shi	Gunma	Japan	370-0829
704	Research Site	Fukuyama-shi	Hiroshima	Japan	721-8511
705	Research Site	Hiroshima-shi	Hiroshima	Japan	734-8551
706	Research Site	Kure-shi	Hiroshima	Japan	737-0023
707	Research Site	Hakodate-shi	Hokkaido	Japan	041-8512
708	Research Site	Sapporo-shi	Hokkaido	Japan	063-0005
709	Research Site	Amagasaki-shi	Hyogo	Japan	660-8550
710	Research Site	Himeji-shi	Hyogo	Japan	670-0981
711	Research Site	Kawanishi-shi	Hyogo	Japan	666-0125
712	Research Site	Nishinomiya-shi	Hyogo	Japan	663-8501
713	Research Site	Takarazuka-shi	Hyogo	Japan	665-0873
714	Research Site	Higashiibaraki-gun	Ibaraki	Japan	311-3193
715	Research Site	Kahoku-gun	Ishikawa	Japan	920-0293
716	Research Site	Kanazawa-shi	Ishikawa	Japan	920-8650
717	Research Site	Morioka-shi	Iwate	Japan	020-0066
718	Research Site	Takamatsu-shi	Kagawa	Japan	760-8557
719	Research Site	Hayama	Kanagawa	Japan	240-0116
720	Research Site	Kawasaki-shi	Kanagawa	Japan	210-0852
721	Research Site	Kawasaki-shi	Kanagawa	Japan	211-8533
722	Research Site	Kawasaki-shi	Kanagawa	Japan	216-8511
723	Research Site	Odawara-shi	Kanagawa	Japan	250-8558
724	Research Site	Sagamihara-shi	Kanagawa	Japan	252-0392
725	Research Site	Sagamihara-shi	Kanagawa	Japan	252-5188
726	Research Site	Yokohama-shi	Kanagawa	Japan	227-8501
727	Research Site	Yokohama-shi	Kanagawa	Japan	231-8682
728	Research Site	Yokohama-shi	Kanagawa	Japan	247-8581
729	Research Site	Nankoku-shi	Kochi	Japan	783-8505
730	Research Site	Kumamoto-shi	Kumamoto	Japan	861-4193
731	Research Site	Sendai-shi	Miyagi	Japan	980-8574
732	Research Site	Nagano-shi	Nagano	Japan	381-8551
733	Research Site	Kashihara-shi	Nara	Japan	634-8522
734	Research Site	Oita-shi	Oita	Japan	870-0192
735	Research Site	Okayama-shi	Okayama	Japan	700-8558
736	Research Site	Naha-shi	Okinawa	Japan	902-8511
737	Research Site	Shimajiri-gun	Okinawa	Japan	901-0493
738	Research Site	Urasoe-shi	Okinawa	Japan	901-2132
739	Research Site	Higashiosaka-shi	Osaka	Japan	579-8056
740	Research Site	Matsubara-shi	Osaka	Japan	580-0032
741	Research Site	Osaka-shi	Osaka	Japan	530-0001
742	Research Site	Osaka-shi	Osaka	Japan	533-0024
743	Research Site	Osaka-shi	Osaka	Japan	540-0006
744	Research Site	Osaka-shi	Osaka	Japan	556-0017
745	Research Site	Osaka-shi	Osaka	Japan	559-0012
746	Research Site	Suita-shi	Osaka	Japan	565-0871
747	Research Site	Saga-shi	Saga	Japan	849-8501
748	Research Site	Ureshino-shi	Saga	Japan	843-0301
749	Research Site	Ageo-shi	Saitama	Japan	362-8588
750	Research Site	Koshigaya-shi	Saitama	Japan	343-8577
751	Research Site	Wako-shi	Saitama	Japan	351-0102
752	Research Site	Kusatsu-shi	Shiga	Japan	525-8585
753	Research Site	Sunto-gun	Shizuoka	Japan	411-8611
754	Research Site	Akishima-shi	Tokyo	Japan	196-0003
755	Research Site	Bunkyo-ku	Tokyo	Japan	113-8519
756	Research Site	Bunkyo-ku	Tokyo	Japan	113-8603
757	Research Site	Chuo-ku	Tokyo	Japan	104-8560
758	Research Site	Fussa-shi	Tokyo	Japan	197-8511
759	Research Site	Hachioji-shi	Tokyo	Japan	192-0918
760	Research Site	Itabashi-ku	Tokyo	Japan	173-8610
761	Research Site	Kodaira-shi	Tokyo	Japan	187-8510
762	Research Site	Meguro-ku	Tokyo	Japan	152-8902
763	Research Site	Minato-ku	Tokyo	Japan	108-8642
764	Research Site	Shinagawa-ku	Tokyo	Japan	140-8522
765	Research Site	Shinjuku-ku	Tokyo	Japan	162-8655
766	Research Site	Toyama-shi	Toyama	Japan	939-8511
767	Research Site	Kaunas		Lithuania	50009
768	Research Site	Klaipeda		Lithuania	92288
769	Research Site	Vilnius		Lithuania	08661
770	Research Site	Vilnius		Lithuania	08861
771	Research Site	Torreon	Coahuila	Mexico	27000
772	Research Site	Mexico City	Distrito Federal	Mexico	06700
773	Research Site	Mexico City	Distrito Federal	Mexico	14080
774	Research Site	Mexico	Distrito Federal	Mexico	11650
775	Research Site	Pachuca	Hidalgo	Mexico	42070
776	Research Site	Guadalajara	Jalisco	Mexico	44280
777	Research Site	Guadalajara	Jalisco	Mexico	44340
778	Research Site	Guadalajara	Jalisco	Mexico	44670
779	Research Site	Zapopan	Jalisco	Mexico	45030
780	Research Site	Monterrey	Nuevo León	Mexico	64060
781	Research Site	Monterrey	Nuevo León	Mexico	64460
782	Research Site	Queretaro	Querétaro	Mexico	76000
783	Research Site	San Luis Potosi	San Luis Potosí	Mexico	78200
784	Research Site	Culiacan	Sinaloa	Mexico	80230
785	Research Site	Xalapa	Veracruz	Mexico	91193
786	Research Site	Aguascalientes		Mexico	20230
787	Research Site	's Hertogenbosch		Netherlands	5223 GZ
788	Research Site	Almelo		Netherlands	7609 PP
789	Research Site	Arnhem		Netherlands	6815 AD
790	Research Site	Breda		Netherlands	4818 CK
791	Research Site	Capelle Aan De IJssel		Netherlands	2906 ZC
792	Research Site	Den Helder		Netherlands	1782 GZ
793	Research Site	Deventer		Netherlands	7416 SE
794	Research Site	Doetinchem		Netherlands	7009 BL
795	Research Site	Emmen		Netherlands	7824 AA
796	Research Site	Goes		Netherlands	4462 RA
797	Research Site	Groningen		Netherlands	9713 GZ
798	Research Site	Groningen		Netherlands	9728 NT
799	Research Site	Leiderdorp		Netherlands	2353 GA
800	Research Site	Nijmegen		Netherlands	6532 SZ
801	Research Site	Tiel		Netherlands	4002 WP
802	Research Site	Tilburg		Netherlands	5022 GC
803	Research Site	Tilburg		Netherlands	5042 AD
804	Research Site	Uden		Netherlands	5406 PT
805	Research Site	Zwolle		Netherlands	8025 AB
806	Research Site	Christchurch		New Zealand	8011
807	Research Site	Papatoetoe, Auckland		New Zealand	2025
808	Research Site	Takapuna, Auckland		New Zealand	0620
809	Research Site	Bialystok		Poland	15-276
810	Research Site	Bytom		Poland	41-902
811	Research Site	Gdansk		Poland	80-262
812	Research Site	Gdynia		Poland	81-157
813	Research Site	Gdynia		Poland	81-423
814	Research Site	Gizycko		Poland	11-500
815	Research Site	Kazimierza Wielka		Poland	28-500
816	Research Site	Kielce		Poland	25-736
817	Research Site	Klodzko		Poland	57-300
818	Research Site	Krakow		Poland	30-069
819	Research Site	Krakow		Poland	30-082
820	Research Site	Krakow		Poland	31-202
821	Research Site	Lodz		Poland	90-549
822	Research Site	Lodz		Poland	91-347
823	Research Site	Lodz		Poland	92-213
824	Research Site	Lublin		Poland	20-078
825	Research Site	Lublin		Poland	20-857
826	Research Site	Miechow		Poland	32-200
827	Research Site	Olawa		Poland	55-200
828	Research Site	Piotrkow Trybunalski		Poland	97-300
829	Research Site	Poznan		Poland	61-848
830	Research Site	Ruda Slaska		Poland	41-709
831	Research Site	Skierniewice		Poland	96-100
832	Research Site	Stalowa Wola		Poland	37-450
833	Research Site	Swidnik		Poland	21-040
834	Research Site	Tarnow		Poland	33-100
835	Research Site	Torun		Poland	87-100
836	Research Site	Warszawa		Poland	02-097
837	Research Site	Warszawa		Poland	04-628
838	Research Site	Wloclawek		Poland	87-800
839	Research Site	Wroclaw		Poland	51-124
840	Research Site	Zabrze		Poland	41-800
841	Research Site	Aveiro		Portugal	3814-501
842	Research Site	Coimbra		Portugal	3000-075
843	Research Site	Covilha		Portugal	6200-251
844	Research Site	Guimaraes		Portugal	4835-044
845	Research Site	Lisboa		Portugal	1449-005
846	Research Site	Lisboa		Portugal	1500-650
847	Research Site	Lisboa		Portugal	1649-035
848	Research Site	Setubal		Portugal	2910-446
849	Research Site	San Juan		Puerto Rico	00926-2832
850	Research Site	Bucarest		Romania	014461
851	Research Site	Bucharest		Romania	050098
852	Research Site	Bucuresti		Romania	021659
853	Research Site	Bucuresti		Romania	022322
854	Research Site	Cluj-Napoca		Romania	400347
855	Research Site	Craiova		Romania	200383
856	Research Site	Craiova		Romania	200642
857	Research Site	Iasi		Romania	700661
858	Research Site	Iasi		Romania	700732
859	Research Site	Oradea		Romania	410169
860	Research Site	Pitesti		Romania	110438
861	Research Site	Targoviste		Romania	130095
862	Research Site	Targu Mures		Romania	540143
863	Research Site	Timisoara		Romania	300079
864	Research Site	Arkhangelsk		Russian Federation	163001
865	Research Site	Barnaul		Russian Federation	656038
866	Research Site	Ekaterinburg		Russian Federation	620102
867	Research Site	Ivanovo		Russian Federation	153012
868	Research Site	Izhevsk		Russian Federation	426063
869	Research Site	Kemerovo		Russian Federation	650002
870	Research Site	Kemerovo		Russian Federation	650099
871	Research Site	Kirov		Russian Federation	610014
872	Research Site	Korolev		Russian Federation	141060
873	Research Site	Krasnodar		Russian Federation	350086
874	Research Site	Lomonosov		Russian Federation	198412
875	Research Site	Moscow		Russian Federation	101990
876	Research Site	Moscow		Russian Federation	117292
877	Research Site	Moscow		Russian Federation	119192
878	Research Site	Moscow		Russian Federation	121552
879	Research Site	Moscow		Russian Federation	123182
880	Research Site	Moscow		Russian Federation	127299
881	Research Site	Moscow		Russian Federation	129090
882	Research Site	Moscow		Russian Federation	129327
883	Research Site	Nizhniy Novgorod		Russian Federation	603076
884	Research Site	Nizhny Novgorod		Russian Federation	603126
885	Research Site	Novosibirsk		Russian Federation	630008
886	Research Site	Novosibirsk		Russian Federation	630087
887	Research Site	Novosibirsk		Russian Federation	630089
888	Research Site	Omsk		Russian Federation	644018
889	Research Site	Saint Petersburg		Russian Federation	194156
890	Research Site	Saint Petersburg		Russian Federation	195112
891	Research Site	Saint Petersburg		Russian Federation	197022
892	Research Site	Saint Petersburg		Russian Federation	198205
893	Research Site	Saint-Petersburg		Russian Federation	192242
894	Research Site	Saint-Petersburg		Russian Federation	196601
895	Research Site	Saint-Petersburg		Russian Federation	197022
896	Research Site	Saint-Petersburg		Russian Federation	199106
897	Research Site	Saratov		Russian Federation	410054
898	Research Site	St. Petersburg		Russian Federation	191015
899	Research Site	Tomsk		Russian Federation	634012
900	Research Site	Village Novoseltsy		Russian Federation	214016
901	Research Site	Vladimir		Russian Federation	600020
902	Research Site	Yaroslavl		Russian Federation	150030
903	Research Site	Banska Bystrica		Slovakia	974 01
904	Research Site	Bardejov		Slovakia	085 01
905	Research Site	Bratislava		Slovakia	811 08
906	Research Site	Bratislava		Slovakia	826 06
907	Research Site	Bratislava		Slovakia	833 48
908	Research Site	Brezno		Slovakia	977 42
909	Research Site	Kosice		Slovakia	040 01
910	Research Site	Levice		Slovakia	934 01
911	Research Site	Nitra		Slovakia	950 01
912	Research Site	Presov		Slovakia	080 01
913	Research Site	Rimavska Sobota		Slovakia	979 01
914	Research Site	Snina		Slovakia	069 01
915	Research Site	Svidnik		Slovakia	089 01
916	Research Site	Trnava		Slovakia	917 75
917	Research Site	Bloemfontein	Free State	South Africa	9301
918	Research Site	Parktown	Gauteng	South Africa	2193
919	Research Site	Soweto	Gauteng	South Africa	2013
920	Research Site	Sunninghill	Gauteng	South Africa	2157
921	Research Site	Durban	KwaZulu-Natal	South Africa	4001
922	Research Site	Umhlanga	KwaZulu-Natal	South Africa	4320
923	Research Site	Parow	Western Cape	South Africa	7505
924	Research Site	Somerset West	Western Cape	South Africa	7130
925	Research Site	Worcester	Western Cape	South Africa	6850
926	Research Site	Cordoba	Andalucía	Spain	14004
927	Research Site	Granada	Andalucía	Spain	18014
928	Research Site	Malaga	Andalucía	Spain	29010
929	Research Site	Sevilla	Andalucía	Spain	41009
930	Research Site	Ubeda	Andalucía	Spain	23400
931	Research Site	Zaragoza	Aragón	Spain	50009
932	Research Site	Oviedo	Asturias	Spain	33011
933	Research Site	La laguna	Canarias	Spain	38320
934	Research Site	Santander	Cantabria	Spain	39008
935	Research Site	Valladolid	Castilla León	Spain	47005
936	Research Site	Barcelona	Cataluña	Spain	08041
937	Research Site	Alicante	Comunidad Valenciana	Spain	03010
938	Research Site	Valencia	Comunidad Valenciana	Spain	46010
939	Research Site	Valencia	Comunidad Valenciana	Spain	46026
940	Research Site	A Coruña	Galicia	Spain	15006
941	Research Site	Santiago de Compostela	Galicia	Spain	15706
942	Research Site	Vigo	Galicia	Spain	36312
943	Research Site	Majadahonda	Madrid	Spain	28222
944	Research Site	El Palmar	Murcia	Spain	30120
945	Research Site	Madrid		Spain	28007
946	Research Site	Madrid		Spain	28040
947	Research Site	Madrid		Spain	28041
948	Research Site	Falun		Sweden	791 82
949	Research Site	Jonkoping		Sweden	553 05
950	Research Site	Lidköping		Sweden	531 85
951	Research Site	Linkoping		Sweden	581 85
952	Research Site	Lund		Sweden	222 21
953	Research Site	Orebro		Sweden	701 85
954	Research Site	Skelleftea		Sweden	931 86
955	Research Site	Basel		Switzerland	4031
956	Research Site	Bern		Switzerland	3010
957	Research Site	Fribourg		Switzerland	1708
958	Research Site	Geneva 14		Switzerland	1211
959	Research Site	Lausanne		Switzerland	1011
960	Research Site	Lugano		Switzerland	6900
961	Research Site	Zurich		Switzerland	8032
962	Research Site	Adana		Turkey	01330
963	Research Site	Afyonkarahisar		Turkey	03218
964	Research Site	Ankara		Turkey	06100
965	Research Site	Ankara		Turkey	06490
966	Research Site	Corum		Turkey	19040
967	Research Site	Eskisehir		Turkey	26040
968	Research Site	Istanbul		Turkey	34096
969	Research Site	Istanbul		Turkey	34098
970	Research Site	Istanbul		Turkey	34200
971	Research Site	Istanbul		Turkey	34865
972	Research Site	Izmir		Turkey	35100
973	Research Site	Izmir		Turkey	35340
974	Research Site	Kirikkale		Turkey	71100
975	Research Site	Kocaeli		Turkey	41380
976	Research Site	Konya		Turkey	42080
977	Research Site	Mersin		Turkey	33343
978	Research Site	Sakarya		Turkey	54100
979	Research Site	Sivas		Turkey	58140
980	Research Site	Van		Turkey	65100
981	Research Site	Dnipropetrovsk		Ukraine	49060
982	Research Site	Ivano-Frankivsk		Ukraine	76018
983	Research Site	Kharkiv		Ukraine	61002
984	Research Site	Kharkiv		Ukraine	61018
985	Research Site	Kharkiv		Ukraine	61039
986	Research Site	Kharkiv		Ukraine	61106
987	Research Site	Kharkiv		Ukraine	61176
988	Research Site	Kyiv		Ukraine	01601
989	Research Site	Kyiv		Ukraine	02091
990	Research Site	Kyiv		Ukraine	02232
991	Research Site	Kyiv		Ukraine	02660
992	Research Site	Kyiv		Ukraine	03151
993	Research Site	Kyiv		Ukraine	03680
994	Research Site	Lutsk		Ukraine	43024
995	Research Site	Uzhgorod		Ukraine	88014
996	Research Site	Vinnytsia		Ukraine	21018
997	Research Site	Vinnytsia		Ukraine	21029
998	Research Site	Vinnytsya		Ukraine	21001
999	Research Site	Zaporizhzhia		Ukraine	69035
1000	Research Site	Zaporizhzhya		Ukraine	69600
1001	Research Site	Ayr		United Kingdom	KA6 6DX
1002	Research Site	Basingstoke		United Kingdom	RG24 9NA
1003	Research Site	Belfast		United Kingdom	BT16 1RH
1004	Research Site	Blackpool		United Kingdom	FY3 8NR
1005	Research Site	Corby		United Kingdom	NN17 2UR
1006	Research Site	Cottingham		United Kingdom	HU16 5JQ
1007	Research Site	Dudley		United Kingdom	DY1 2HQ
1008	Research Site	Dundee		United Kingdom	DD1 9SY
1009	Research Site	Exeter		United Kingdom	EX2 5DW
1010	Research Site	Gillingham		United Kingdom	ME7 5NY
1011	Research Site	Glasgow		United Kingdom	G75 8RG
1012	Research Site	Harlow		United Kingdom	CM20 1QX
1013	Research Site	High Wycombe		United Kingdom	HP11 2TT
1014	Research Site	London		United Kingdom	N18 1QX
1015	Research Site	London		United Kingdom	SW3 6NP
1016	Research Site	London		United Kingdom	W12 0HS
1017	Research Site	Merthyr Tydfil		United Kingdom	CF47 9DT
1018	Research Site	Newport		United Kingdom	PO30 5TG
1019	Research Site	Northampton		United Kingdom	NN1 5BD
1020	Research Site	Northwood		United Kingdom	HA6 2RN
1021	Research Site	Norwich		United Kingdom	NR4 7UY
1022	Research Site	Peterborough		United Kingdom	PE3 9GZ
1023	Research Site	Portsmouth		United Kingdom	PO6 3LY
1024	Research Site	Romford		United Kingdom	RM1 3PJ
1025	Research Site	Sheffield		United Kingdom	S5 7AU
1026	Research Site	Shipley		United Kingdom	BD18 3SA
1027	Research Site	Sidcup		United Kingdom	DA14 6LT
1028	Research Site	Solihull		United Kingdom	B91 2JL
1029	Research Site	Stevenage		United Kingdom	SG1 4AB
1030	Research Site	Sunderland		United Kingdom	SR4 7TP
1031	Research Site	Swindon		United Kingdom	SN3 6BB
1032	Research Site	Taunton		United Kingdom	TA1 5DA
1033	Research Site	Torquay		United Kingdom	TQ2 7AA
1034	Research Site	Worcester		United Kingdom	WR5 1DD

Sponsors and Collaborators

• Cytokinetics

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

• Study Protocol - Nov 13, 2018
• Statistical Analysis Plan - Jun 16, 2020

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

• Teerlink JR, Diaz R, Felker GM, McMurray JJV, Metra M, Solomon SD, Biering-Sørensen T, Böhm M, Bonderman D, Fang JC, Lanfear DE, Lund M, Momomura SI, O'Meara E, Ponikowski P, Spinar J, Flores-Arredondo JH, Claggett BL, Heitner SB, Kupfer S, Abbasi SA, Malik FI; GALACTIC-HF Investigators. Effect of Ejection Fraction on Clinical Outcomes in Patients Treated With Omecamtiv Mecarbil in GALACTIC-HF. J Am Coll Cardiol. 2021 Jul 13;78(2):97-108. doi: 10.1016/j.jacc.2021.04.065. Epub 2021 May 17.

• Responsible Party: Cytokinetics
• ClinicalTrials.gov Identifier: NCT02929329
• Other Study ID Numbers: 20110203; 2016-002299-28
• First Posted: Oct 11, 2016
• Last Update Posted: Nov 5, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Recruitment Details

A total of 11,121 patients underwent screening at 944 sites in 35 countries. Of these patients, 8,256 were randomized, but 24 patients from one site were excluded because of Good Clinical Practice violations and are not included in the data reported below.

Pre-assignment Detail

Participants were randomly assigned in a 1:1 ratio to receive either oral omecamtiv mecarbil (OM) or placebo. Randomization was stratified by randomization setting (currently hospitalized for heart failure [HF] or recently and not currently hospitalized for HF) and region (United States and Canada; Latin America; Western Europe, South Africa, and Australasia; Eastern Europe including Russia; Asia).

Arm/Group Title	Placebo	Omecamtiv Mecarbil
Arm/Group Description	Participants received matching placebo tablets twice a day (BID).	Participants received oral omecamtiv mecarbil BID. The starting dose was 25 mg; the dose may have been adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
Period Title: Overall Study
STARTED	4112	4120
Received Treatment	4101	4110
COMPLETED	3008	3028
NOT COMPLETED	1104	1092

Baseline Characteristics

Arm/Group Title	Placebo	Omecamtiv Mecarbil	Total
Arm/Group Description	Participants received matching placebo tablets (BID).	Participants received oral omecamtiv mecarbil BID. The starting dose was 25 mg; the dose may have been adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.	Total of all reporting groups
Overall Participants	4112	4120	8232
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.5 (11.4)	64.5 (11.3)	64.5 (11.4)
Age, Customized (Count of Participants)
18 to 64 years	1873 45.5%	1874 45.5%	3747 45.5%
65 to 84 years	2211 53.8%	2220 53.9%	4431 53.8%
85 years and over	28 0.7%	26 0.6%	54 0.7%
Sex: Female, Male (Count of Participants)
Female	874 21.3%	875 21.2%	1749 21.2%
Male	3238 78.7%	3245 78.8%	6483 78.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	885 21.5%	886 21.5%	1771 21.5%
Not Hispanic or Latino	3227 78.5%	3234 78.5%	6461 78.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	38 0.9%	35 0.8%	73 0.9%
Asian	355 8.6%	355 8.6%	710 8.6%
Black or African American	277 6.7%	285 6.9%	562 6.8%
Multiple	96 2.3%	99 2.4%	195 2.4%
Native Hawaiian or Other Pacific Islander	6 0.1%	7 0.2%	13 0.2%
White	3201 77.8%	3196 77.6%	6397 77.7%
Other	139 3.4%	143 3.5%	282 3.4%
Randomization Setting (Count of Participants)
Currently hospitalized for heart failure	1050 25.5%	1051 25.5%	2101 25.5%
Recently and not currently hospitalized for heart failure	3062 74.5%	3069 74.5%	6131 74.5%
Region (Count of Participants)
United States and Canada	693 16.9%	693 16.8%	1386 16.8%
Latin America	787 19.1%	787 19.1%	1574 19.1%
Western Europe, South Africa, and Australasia	960 23.3%	961 23.3%	1921 23.3%
Eastern Europe including Russia	1337 32.5%	1344 32.6%	2681 32.6%
Asia	335 8.1%	335 8.1%	670 8.1%

Outcome Measures

1. Primary Outcome

Title	Time to Cardiovascular Death or First Heart Failure Event
Description	The primary outcome was a composite of a heart-failure (HF) event or cardiovascular (CV) death, whichever occurred first, in a time-to-event analysis. A heart-failure event was defined as an urgent clinic visit, emergency department visit, or hospitalization for subjectively and objectively worsening heart failure leading to treatment intensification beyond a change in oral diuretic therapy. All deaths and HF events were adjudicated by an independent external clinical events committee (CEC) at the Duke Clinical Research Institute, using standardized definitions based on the recent American College of Cardiology/American Heart Association (ACC/AHA) standards for endpoint definitions in cardiovascular clinical trials. Time to cardiovascular death or first HF event was analyzed using Kaplan-Meier (KM) methods. Since the median was not calculated, the percentage of participants with a positively adjudicated event during the study is reported.
Time Frame	From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Placebo	Omecamtiv Mecarbil
Arm/Group Description	Participants received matching placebo tablets (BID).	Participants received oral omecamtiv mecarbil BID. The starting dose was 25 mg; the dose may have been adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
Measure Participants	4112	4120
Number [percentage of participants]	39.1 1%	37.0 0.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omecamtiv Mecarbil
	Comments
	Type of Statistical Test	Superiority
	Comments	The overall type I error was 0.05 for 2-sided testing across primary and secondary outcomes. Control for multiple comparisons was achieved using the following testing algorithm: if the primary outcome met the P-value threshold of 0.05, the alpha error would be divided unequally between cardiovascular death (96% of the overall alpha error, or 0.048) and change from baseline to week 24 in the Kansas City Cardiomyopathy Questionnaire total symptom score (4% of the overall alpha error, or 0.002).
Statistical Test of Hypothesis	p-Value	0.0252
	Comments
	Method	Regression, Cox
	Comments	Stratified by randomization setting and region, including terms for baseline estimated glomerular filtration rate (eGFR) and treatment group.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.86 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox proportional-hazards model with baseline hazards stratified according to the randomization setting and geographic region and with the treatment group and baseline eGFR as covariates.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omecamtiv Mecarbil
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0211
	Comments
	Method	Stratified log-rank test
	Comments	Log-rank test stratified by randomization setting and region.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omecamtiv Mecarbil
	Comments	Competing risk subdistribution hazard ratio and associated 95% confidence intervals for treatment were computed. Deaths not included in the endpoint were considered as the competing risk.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.86 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox proportional-hazards model with baseline hazards stratified according to the randomization setting and geographic region and with the treatment group and baseline eGFR as covariates.

2. Secondary Outcome

Title	Time to Cardiovascular Death
Description	Cardiovascular death includes acute myocardial infarction (MI), sudden cardiac death, death due to heart failure, death due to stroke, death due to cardiovascular (CV) procedures, death due to CV hemorrhage, and death due to other CV causes. All deaths were adjudicated by an independent external clinical-events committee at the Duke Clinical Research Institute, using standardized definitions based on the recent ACC/AHA standards for endpoint definitions in cardiovascular clinical trials. Time to cardiovascular death was analyzed using Kaplan-Meier methods. Since the median was not calculated, the percentage of participants with a positively adjudicated event during the study is reported.
Time Frame	From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Placebo	Omecamtiv Mecarbil
Arm/Group Description	Participants received matching placebo tablets (BID).	Participants received oral omecamtiv mecarbil BID. The starting dose was 25 mg; the dose may have been adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
Measure Participants	4112	4120
Number [percentage of participants]	19.4 0.5%	19.6 0.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omecamtiv Mecarbil
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8555
	Comments	If significance for the primary outcome was determined, cardiovascular death was tested against an alpha of 0.048.
	Method	Regression, Cox
	Comments	Stratified by randomization setting and region, including terms for baseline eGFR and treatment group.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox proportional-hazards model with baseline hazards stratified according to the randomization setting and geographic region and with the treatment group and baseline eGFR as covariates.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omecamtiv Mecarbil
	Comments	Competing risk subdistribution hazard ratio and associated 95% confidence intervals for treatment were computed. Deaths not included in the endpoint were considered as the competing risk.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox proportional-hazards model with baseline hazards stratified according to the randomization setting and geographic region and with the treatment group and baseline eGFR as covariates.

3. Secondary Outcome

Title	Change From Baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ TSS) at Week 24
Description	The Kansas City Cardiomyopathy Questionnaire is a self-administered questionnaire with a 2-week recall period that includes 23 items that map to 7 domains: symptom frequency; symptom burden; symptom stability; physical limitations; social limitations; quality of life; and self-efficacy (the patient's understanding of how to manage their heart failure). The symptom frequency and symptom burden domains are merged into a total symptom score. Scores are represented on a 0-to-100-point scale, where lower scores represent more frequent and severe symptoms and scores of 100 indicate no symptoms. The change from baseline in KCCQ TSS was analyzed separately for each randomization setting (inpatient and outpatient). Least squares means are from the mixed model which includes baseline total symptom score value, region, baseline eGFR, scheduled visit, treatment group and interaction of treatment with scheduled visit as covariates.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo: Oupatients	Omecamtiv Mecarbil: Outpatients	Placebo: Inpatients	Omecamtiv Mecarbil: Inpatients
Arm/Group Description	Participants who had either made an urgent visit to the emergency department or been hospitalized for heart failure within 1 year before screening received placebo tablets twice a day.	Participants who had either made an urgent visit to the emergency department or been hospitalized for heart failure within 1 year before screening received oral omecamtiv mecarbil twice daily. The starting dose was 25 mg; the dose could be adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.	Participants who were currently hospitalized for heart failure received placebo tablets twice a day.	Participants who were currently hospitalized for heart failure received oral omecamtiv mecarbil twice daily. The starting dose was 25 mg; the dose could be adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
Measure Participants	2704	2715	835	868
Least Squares Mean (Standard Error) [scores on a scale]	6.29 (0.34)	5.83 (0.34)	21.15 (0.71)	23.65 (0.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omecamtiv Mecarbil
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95%; -1.40 to 0.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.48
	Estimation Comments	Treatment difference = Omecamtiv mecarbil - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo: Inpatients, Omecamtiv Mecarbil: Inpatients
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.50
	Confidence Interval	(2-Sided) 95%; 0.54 to 4.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.00
	Estimation Comments	Treatment difference = Omecamtiv mecarbil - Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omecamtiv Mecarbil, Placebo: Inpatients, Omecamtiv Mecarbil: Inpatients
	Comments
	Type of Statistical Test	Superiority
	Comments	If significance for the primary outcome was determined, change from baseline in the KCCQ total symptom score was tested against an alpha of 0.002.
Statistical Test of Hypothesis	p-Value	0.0278
	Comments
	Method	Omnibus F-test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omecamtiv Mecarbil, Placebo: Inpatients, Omecamtiv Mecarbil: Inpatients
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Pooled treatment difference
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; -2.55 to 4.51
	Parameter Dispersion	Type: Value:
	Estimation Comments	Overall pooled estimate of treatment difference (Omecamtiv mecarbil - Placebo) using random effects meta-analysis approach.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omecamtiv Mecarbil
	Comments	As a sensitivity for missing data due to death, joint longitudinal and survival models were fit using KCCQ TSS observed values with random subject slopes and intercepts for the longitudinal models with terms for baseline eGFR, region, and treatment by slope. The survival models were fit for all-cause death with baseline eGFR and treatment in the proportional hazard part of the models, KCCQ TSS modeled values as the shared parameterization, stratified by region with Weibull baseline functions.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95%; -1.62 to 0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference = Omecamtiv mecarbil - Placebo

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo: Inpatients, Omecamtiv Mecarbil: Inpatients
	Comments	As a sensitivity for missing data due to death, joint longitudinal and survival models were fit using KCCQ TSS observed values with random subject slopes and intercepts for the longitudinal models with terms for baseline eGFR, region, and treatment by slope. The survival models were fit for all-cause death with baseline eGFR and treatment in the proportional hazard part of the models, KCCQ TSS modeled values as the shared parameterization, stratified by region with Weibull baseline functions.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	2.31
	Confidence Interval	(2-Sided) 95%; 0.80 to 3.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment difference = Omecamtiv mecarbil - Placebo

4. Secondary Outcome

Title	Time to First Heart Failure Hospitalization
Description	A HF hospitalization is defined as an event that met all of the following criteria: The participant was admitted to the hospital with a primary diagnosis of HF; The length of stay in the hospital extended for at least 24 hours; The participant exhibited documented new or worsening symptoms due to HF on presentation; The participant had objective evidence of new or worsening HF; The participant received initiation or intensification of treatment specifically for HF, including an intravenous diuretic or vasoactive agent, mechanical or surgical intervention, or mechanical fluid removal. Events were adjudicated by an independent external CEC at the Duke Clinical Research Institute using standardized definitions based on the ACC/AHA standards for endpoint definitions in CV clinical trials. Time to first HF hospitalization was analyzed using KM methods. Since the median was not calculated, the percentage of participants with a positively adjudicated event is reported.
Time Frame	From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Placebo	Omecamtiv Mecarbil
Arm/Group Description	Participants received matching placebo tablets (BID).	Participants received oral omecamtiv mecarbil BID. The starting dose was 25 mg; the dose may have been adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
Measure Participants	4112	4120
Number [percentage of participants]	28.7 0.7%	27.7 0.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omecamtiv Mecarbil
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1902
	Comments	If statistical significance was achieved for both the time to CV death and change from baseline in the KCCQ TSS, time to first heart failure hospitalization was to be tested at the full alpha.
	Method	Regression, Cox
	Comments	Stratified by randomization setting and region, including terms for baseline eGFR and treatment group.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox proportional-hazards model with baseline hazards stratified according to the randomization setting and geographic region and with the trial group and the baseline eGFR as covariates.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omecamtiv Mecarbil
	Comments	Competing risk subdistribution hazard ratio and associated 95% confidence intervals for treatment were computed. Deaths not included in the endpoint are considered as the competing risk.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox proportional-hazards model with baseline hazards stratified according to the randomization setting and geographic region and with the trial group and the baseline eGFR as covariates.

5. Secondary Outcome

Title	Time to All-cause Death
Description	All events were adjudicated by an independent external clinical-events committee at the Duke Clinical Research Institute, using standardized definitions based on the recent ACC/AHA standards for endpoint definitions in cardiovascular clinical trials. Time to all-cause death was analyzed using Kaplan-Meier methods. Since the median was not calculated, the percentage of participants with an event are reported. Events that occurred up to the earliest of last confirmed survival status date or analysis cut-off date (07 August 2020) are included.
Time Frame	From randomization up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Placebo	Omecamtiv Mecarbil
Arm/Group Description	Participants received matching placebo tablets (BID).	Participants received oral omecamtiv mecarbil BID. The starting dose was 25 mg; the dose may have been adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
Measure Participants	4112	4120
Number [percentage of participants]	25.9 0.6%	25.9 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omecamtiv Mecarbil
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9633
	Comments	If time to first heart failure hospitalization was statistically significant, time to all-cause death was to be tested with the same alpha as time to first heart failure hospitalization.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox proportional-hazards model with baseline hazards stratified according to the randomization setting and geographic region and with the trial group and the baseline eGFR as covariates.

Adverse Events

Time Frame	All-cause mortality is reported from randomization until end of study (27 August 2020); median (min, max) time on study was 21.8 (0, 42) months. Adverse events are reported from first dose of study drug until 30 days after last dose; median (min, max) treatment duration was 19.5 (0, 42) months.
Adverse Event Reporting Description	All-cause mortality is reported for all participants randomized in the study, excluding 24 participants due to GCP violations. All-cause mortality includes all deaths that occurred during the study including any that occurred after the efficacy analysis cut-off date. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Arm/Group Title	Placebo		Omecamtiv Mecarbil
Arm/Group Description	Participants received matching placebo tablets (BID).		Participants received oral omecamtiv mecarbil BID. The starting dose was 25 mg; the dose may have been adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
All Cause Mortality
	Placebo		Omecamtiv Mecarbil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1078/4112 (26.2%)		1078/4120 (26.2%)
Serious Adverse Events
	Placebo		Omecamtiv Mecarbil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2435/4101 (59.4%)		2373/4110 (57.7%)
Blood and lymphatic system disorders
Anaemia	28/4101 (0.7%)		34/4110 (0.8%)
Anaemia of chronic disease	2/4101 (0%)		0/4110 (0%)
Anaemia vitamin B12 deficiency	1/4101 (0%)		1/4110 (0%)
Blood loss anaemia	2/4101 (0%)		2/4110 (0%)
Coagulopathy	0/4101 (0%)		3/4110 (0.1%)
Cold type haemolytic anaemia	1/4101 (0%)		0/4110 (0%)
Hypercoagulation	0/4101 (0%)		1/4110 (0%)
Hypochromic anaemia	1/4101 (0%)		2/4110 (0%)
Immune thrombocytopenia	0/4101 (0%)		1/4110 (0%)
Iron deficiency anaemia	3/4101 (0.1%)		3/4110 (0.1%)
Leukopenia	1/4101 (0%)		0/4110 (0%)
Lymphadenopathy	0/4101 (0%)		2/4110 (0%)
Microcytic anaemia	1/4101 (0%)		0/4110 (0%)
Neutropenia	0/4101 (0%)		1/4110 (0%)
Normochromic anaemia	1/4101 (0%)		0/4110 (0%)
Normochromic normocytic anaemia	2/4101 (0%)		0/4110 (0%)
Normocytic anaemia	2/4101 (0%)		0/4110 (0%)
Pancytopenia	1/4101 (0%)		1/4110 (0%)
Splenic infarction	2/4101 (0%)		0/4110 (0%)
Spontaneous haematoma	1/4101 (0%)		2/4110 (0%)
Thrombocytopenia	5/4101 (0.1%)		1/4110 (0%)
Cardiac disorders
Acute coronary syndrome	12/4101 (0.3%)		11/4110 (0.3%)
Acute left ventricular failure	16/4101 (0.4%)		9/4110 (0.2%)
Acute myocardial infarction	64/4101 (1.6%)		71/4110 (1.7%)
Acute right ventricular failure	0/4101 (0%)		2/4110 (0%)
Angina pectoris	40/4101 (1%)		41/4110 (1%)
Angina unstable	49/4101 (1.2%)		63/4110 (1.5%)
Aortic valve disease	1/4101 (0%)		0/4110 (0%)
Aortic valve disease mixed	1/4101 (0%)		1/4110 (0%)
Aortic valve incompetence	1/4101 (0%)		1/4110 (0%)
Aortic valve stenosis	3/4101 (0.1%)		3/4110 (0.1%)
Arrhythmia	6/4101 (0.1%)		4/4110 (0.1%)
Arrhythmia supraventricular	3/4101 (0.1%)		4/4110 (0.1%)
Arteriosclerosis coronary artery	7/4101 (0.2%)		2/4110 (0%)
Atrial fibrillation	113/4101 (2.8%)		94/4110 (2.3%)
Atrial flutter	25/4101 (0.6%)		23/4110 (0.6%)
Atrial tachycardia	9/4101 (0.2%)		9/4110 (0.2%)
Atrial thrombosis	2/4101 (0%)		1/4110 (0%)
Atrioventricular block	1/4101 (0%)		0/4110 (0%)
Atrioventricular block complete	12/4101 (0.3%)		14/4110 (0.3%)
Atrioventricular block second degree	0/4101 (0%)		3/4110 (0.1%)
Bradyarrhythmia	5/4101 (0.1%)		1/4110 (0%)
Bradycardia	3/4101 (0.1%)		8/4110 (0.2%)
Bundle branch block left	5/4101 (0.1%)		1/4110 (0%)
Cardiac amyloidosis	0/4101 (0%)		1/4110 (0%)
Cardiac aneurysm	1/4101 (0%)		0/4110 (0%)
Cardiac arrest	64/4101 (1.6%)		50/4110 (1.2%)
Cardiac asthma	1/4101 (0%)		2/4110 (0%)
Cardiac disorder	3/4101 (0.1%)		0/4110 (0%)
Cardiac failure	1045/4101 (25.5%)		988/4110 (24%)
Cardiac failure acute	251/4101 (6.1%)		212/4110 (5.2%)
Cardiac failure chronic	170/4101 (4.1%)		156/4110 (3.8%)
Cardiac failure congestive	154/4101 (3.8%)		147/4110 (3.6%)
Cardiac flutter	1/4101 (0%)		0/4110 (0%)
Cardiac tamponade	2/4101 (0%)		1/4110 (0%)
Cardiac valve disease	1/4101 (0%)		1/4110 (0%)
Cardiac ventricular thrombosis	2/4101 (0%)		1/4110 (0%)
Cardio-respiratory arrest	14/4101 (0.3%)		9/4110 (0.2%)
Cardiogenic shock	68/4101 (1.7%)		75/4110 (1.8%)
Cardiomyopathy	8/4101 (0.2%)		12/4110 (0.3%)
Cardiopulmonary failure	6/4101 (0.1%)		3/4110 (0.1%)
Cardiorenal syndrome	10/4101 (0.2%)		14/4110 (0.3%)
Cardiovascular insufficiency	2/4101 (0%)		1/4110 (0%)
Chordae tendinae rupture	0/4101 (0%)		1/4110 (0%)
Chronic left ventricular failure	8/4101 (0.2%)		6/4110 (0.1%)
Chronotropic incompetence	0/4101 (0%)		1/4110 (0%)
Conduction disorder	0/4101 (0%)		1/4110 (0%)
Congestive cardiomyopathy	24/4101 (0.6%)		14/4110 (0.3%)
Coronary artery disease	24/4101 (0.6%)		26/4110 (0.6%)
Coronary artery insufficiency	1/4101 (0%)		0/4110 (0%)
Coronary artery occlusion	2/4101 (0%)		1/4110 (0%)
Coronary artery stenosis	10/4101 (0.2%)		6/4110 (0.1%)
Extrasystoles	0/4101 (0%)		1/4110 (0%)
Hypertensive heart disease	3/4101 (0.1%)		0/4110 (0%)
Intracardiac thrombus	1/4101 (0%)		1/4110 (0%)
Ischaemic cardiomyopathy	8/4101 (0.2%)		9/4110 (0.2%)
Left ventricular dysfunction	3/4101 (0.1%)		1/4110 (0%)
Left ventricular failure	4/4101 (0.1%)		4/4110 (0.1%)
Low cardiac output syndrome	3/4101 (0.1%)		2/4110 (0%)
Mitral valve incompetence	8/4101 (0.2%)		9/4110 (0.2%)
Myocardial fibrosis	3/4101 (0.1%)		2/4110 (0%)
Myocardial infarction	54/4101 (1.3%)		36/4110 (0.9%)
Myocardial ischaemia	10/4101 (0.2%)		12/4110 (0.3%)
Myocarditis	0/4101 (0%)		1/4110 (0%)
Palpitations	3/4101 (0.1%)		2/4110 (0%)
Paroxysmal arrhythmia	1/4101 (0%)		0/4110 (0%)
Pericardial effusion	1/4101 (0%)		2/4110 (0%)
Pericardial haemorrhage	1/4101 (0%)		1/4110 (0%)
Pericarditis	1/4101 (0%)		1/4110 (0%)
Pericarditis constrictive	0/4101 (0%)		1/4110 (0%)
Postinfarction angina	0/4101 (0%)		1/4110 (0%)
Prinzmetal angina	1/4101 (0%)		1/4110 (0%)
Prosthetic cardiac valve thrombosis	1/4101 (0%)		0/4110 (0%)
Pulseless electrical activity	2/4101 (0%)		1/4110 (0%)
Right ventricular dysfunction	0/4101 (0%)		1/4110 (0%)
Right ventricular failure	1/4101 (0%)		1/4110 (0%)
Sinus arrest	1/4101 (0%)		0/4110 (0%)
Sinus bradycardia	1/4101 (0%)		2/4110 (0%)
Sinus node dysfunction	2/4101 (0%)		5/4110 (0.1%)
Sinus tachycardia	2/4101 (0%)		2/4110 (0%)
Supraventricular extrasystoles	2/4101 (0%)		1/4110 (0%)
Supraventricular tachyarrhythmia	1/4101 (0%)		2/4110 (0%)
Supraventricular tachycardia	11/4101 (0.3%)		8/4110 (0.2%)
Tachyarrhythmia	2/4101 (0%)		1/4110 (0%)
Tachycardia	5/4101 (0.1%)		2/4110 (0%)
Tricuspid valve incompetence	1/4101 (0%)		1/4110 (0%)
Trifascicular block	0/4101 (0%)		1/4110 (0%)
Ventricular arrhythmia	18/4101 (0.4%)		24/4110 (0.6%)
Ventricular extrasystoles	9/4101 (0.2%)		8/4110 (0.2%)
Ventricular fibrillation	49/4101 (1.2%)		30/4110 (0.7%)
Ventricular flutter	1/4101 (0%)		2/4110 (0%)
Ventricular tachyarrhythmia	7/4101 (0.2%)		7/4110 (0.2%)
Ventricular tachycardia	129/4101 (3.1%)		106/4110 (2.6%)
Congenital, familial and genetic disorders
Congenital megaureter	0/4101 (0%)		1/4110 (0%)
Hydrocele	0/4101 (0%)		1/4110 (0%)
Hypertrophic cardiomyopathy	0/4101 (0%)		1/4110 (0%)
Myocardial bridging	1/4101 (0%)		0/4110 (0%)
Non-compaction cardiomyopathy	1/4101 (0%)		1/4110 (0%)
Ear and labyrinth disorders
Deafness unilateral	0/4101 (0%)		1/4110 (0%)
Sudden hearing loss	1/4101 (0%)		0/4110 (0%)
Vertigo	3/4101 (0.1%)		3/4110 (0.1%)
Vertigo positional	1/4101 (0%)		1/4110 (0%)
Vestibular disorder	0/4101 (0%)		1/4110 (0%)
Endocrine disorders
Basedow's disease	1/4101 (0%)		0/4110 (0%)
Goitre	3/4101 (0.1%)		0/4110 (0%)
Hypercalcaemia of malignancy	1/4101 (0%)		0/4110 (0%)
Hyperthyroidism	2/4101 (0%)		4/4110 (0.1%)
Hypothyroidism	3/4101 (0.1%)		1/4110 (0%)
Thyroiditis	0/4101 (0%)		1/4110 (0%)
Thyrotoxic crisis	1/4101 (0%)		0/4110 (0%)
Eye disorders
Amaurosis fugax	1/4101 (0%)		1/4110 (0%)
Arteriosclerotic retinopathy	0/4101 (0%)		1/4110 (0%)
Cataract	9/4101 (0.2%)		8/4110 (0.2%)
Cataract diabetic	1/4101 (0%)		0/4110 (0%)
Diabetic retinopathy	0/4101 (0%)		1/4110 (0%)
Diplopia	0/4101 (0%)		1/4110 (0%)
Eye inflammation	0/4101 (0%)		1/4110 (0%)
Glaucoma	0/4101 (0%)		2/4110 (0%)
Iridodialysis	0/4101 (0%)		1/4110 (0%)
Iris disorder	0/4101 (0%)		1/4110 (0%)
Macular fibrosis	1/4101 (0%)		0/4110 (0%)
Ocular hypertension	1/4101 (0%)		0/4110 (0%)
Pterygium	0/4101 (0%)		1/4110 (0%)
Retinal detachment	0/4101 (0%)		1/4110 (0%)
Scleromalacia	1/4101 (0%)		0/4110 (0%)
Ulcerative keratitis	1/4101 (0%)		0/4110 (0%)
Visual impairment	0/4101 (0%)		1/4110 (0%)
Vitreous haematoma	0/4101 (0%)		1/4110 (0%)
Vitreous haemorrhage	0/4101 (0%)		2/4110 (0%)
Gastrointestinal disorders
Abdominal adhesions	1/4101 (0%)		1/4110 (0%)
Abdominal discomfort	2/4101 (0%)		1/4110 (0%)
Abdominal distension	3/4101 (0.1%)		3/4110 (0.1%)
Abdominal hernia	3/4101 (0.1%)		0/4110 (0%)
Abdominal incarcerated hernia	0/4101 (0%)		1/4110 (0%)
Abdominal pain	13/4101 (0.3%)		6/4110 (0.1%)
Abdominal pain upper	5/4101 (0.1%)		6/4110 (0.1%)
Abnormal faeces	0/4101 (0%)		1/4110 (0%)
Acute abdomen	0/4101 (0%)		2/4110 (0%)
Anal fistula	1/4101 (0%)		0/4110 (0%)
Anorectal disorder	0/4101 (0%)		1/4110 (0%)
Ascites	2/4101 (0%)		3/4110 (0.1%)
Chronic gastritis	1/4101 (0%)		1/4110 (0%)
Colitis	1/4101 (0%)		1/4110 (0%)
Colitis ischaemic	1/4101 (0%)		1/4110 (0%)
Colitis microscopic	0/4101 (0%)		1/4110 (0%)
Colitis ulcerative	1/4101 (0%)		0/4110 (0%)
Constipation	7/4101 (0.2%)		5/4110 (0.1%)
Crohn's disease	0/4101 (0%)		1/4110 (0%)
Dental caries	0/4101 (0%)		1/4110 (0%)
Diabetic gastroparesis	1/4101 (0%)		0/4110 (0%)
Diarrhoea	12/4101 (0.3%)		6/4110 (0.1%)
Dieulafoy's vascular malformation	0/4101 (0%)		1/4110 (0%)
Diverticular perforation	2/4101 (0%)		1/4110 (0%)
Diverticulum intestinal	1/4101 (0%)		2/4110 (0%)
Diverticulum intestinal haemorrhagic	1/4101 (0%)		0/4110 (0%)
Duodenal ulcer haemorrhage	2/4101 (0%)		1/4110 (0%)
Duodenitis	1/4101 (0%)		1/4110 (0%)
Dyspepsia	1/4101 (0%)		1/4110 (0%)
Dysphagia	1/4101 (0%)		4/4110 (0.1%)
Enterocolitis	3/4101 (0.1%)		1/4110 (0%)
Epiploic appendagitis	0/4101 (0%)		1/4110 (0%)
Erosive oesophagitis	1/4101 (0%)		0/4110 (0%)
Food poisoning	1/4101 (0%)		0/4110 (0%)
Gastric disorder	1/4101 (0%)		1/4110 (0%)
Gastric haemorrhage	1/4101 (0%)		1/4110 (0%)
Gastric polyps	2/4101 (0%)		1/4110 (0%)
Gastric ulcer	1/4101 (0%)		5/4110 (0.1%)
Gastric ulcer haemorrhage	2/4101 (0%)		2/4110 (0%)
Gastric ulcer perforation	1/4101 (0%)		1/4110 (0%)
Gastritis	7/4101 (0.2%)		4/4110 (0.1%)
Gastritis erosive	1/4101 (0%)		0/4110 (0%)
Gastritis haemorrhagic	0/4101 (0%)		2/4110 (0%)
Gastrointestinal angiodysplasia	2/4101 (0%)		0/4110 (0%)
Gastrointestinal disorder	0/4101 (0%)		1/4110 (0%)
Gastrointestinal haemorrhage	14/4101 (0.3%)		18/4110 (0.4%)
Gastrointestinal necrosis	1/4101 (0%)		0/4110 (0%)
Gastrointestinal obstruction	0/4101 (0%)		1/4110 (0%)
Gastrooesophageal reflux disease	7/4101 (0.2%)		3/4110 (0.1%)
Gingival bleeding	1/4101 (0%)		0/4110 (0%)
Haematemesis	0/4101 (0%)		1/4110 (0%)
Haematochezia	2/4101 (0%)		1/4110 (0%)
Haemoperitoneum	0/4101 (0%)		1/4110 (0%)
Haemorrhagic erosive gastritis	1/4101 (0%)		0/4110 (0%)
Haemorrhoidal haemorrhage	1/4101 (0%)		2/4110 (0%)
Haemorrhoids	0/4101 (0%)		2/4110 (0%)
Hernial eventration	1/4101 (0%)		0/4110 (0%)
Hiatus hernia	1/4101 (0%)		3/4110 (0.1%)
Ileus	5/4101 (0.1%)		3/4110 (0.1%)
Ileus paralytic	0/4101 (0%)		1/4110 (0%)
Impaired gastric emptying	0/4101 (0%)		1/4110 (0%)
Incarcerated umbilical hernia	0/4101 (0%)		1/4110 (0%)
Inguinal hernia	9/4101 (0.2%)		10/4110 (0.2%)
Inguinal hernia strangulated	0/4101 (0%)		1/4110 (0%)
Intestinal angina	0/4101 (0%)		1/4110 (0%)
Intestinal haemorrhage	2/4101 (0%)		1/4110 (0%)
Intestinal infarction	1/4101 (0%)		0/4110 (0%)
Intestinal ischaemia	2/4101 (0%)		4/4110 (0.1%)
Intestinal obstruction	6/4101 (0.1%)		4/4110 (0.1%)
Intestinal perforation	1/4101 (0%)		1/4110 (0%)
Intra-abdominal haemorrhage	1/4101 (0%)		0/4110 (0%)
Intussusception	0/4101 (0%)		1/4110 (0%)
Irritable bowel syndrome	0/4101 (0%)		2/4110 (0%)
Ischaemic enteritis	0/4101 (0%)		1/4110 (0%)
Large intestine perforation	1/4101 (0%)		1/4110 (0%)
Large intestine polyp	3/4101 (0.1%)		4/4110 (0.1%)
Lower gastrointestinal haemorrhage	2/4101 (0%)		3/4110 (0.1%)
Lower gastrointestinal perforation	1/4101 (0%)		0/4110 (0%)
Mechanical ileus	0/4101 (0%)		1/4110 (0%)
Melaena	1/4101 (0%)		1/4110 (0%)
Mesenteric arterial occlusion	0/4101 (0%)		2/4110 (0%)
Mesenteric artery embolism	2/4101 (0%)		0/4110 (0%)
Mesenteric vascular insufficiency	1/4101 (0%)		0/4110 (0%)
Nausea	1/4101 (0%)		1/4110 (0%)
Necrotising oesophagitis	0/4101 (0%)		1/4110 (0%)
Obstructive pancreatitis	1/4101 (0%)		1/4110 (0%)
Oesophageal motility disorder	0/4101 (0%)		1/4110 (0%)
Oesophageal spasm	0/4101 (0%)		1/4110 (0%)
Oesophageal ulcer haemorrhage	1/4101 (0%)		0/4110 (0%)
Oesophageal varices haemorrhage	1/4101 (0%)		0/4110 (0%)
Oesophagitis	1/4101 (0%)		0/4110 (0%)
Pancreatitis	1/4101 (0%)		0/4110 (0%)
Pancreatitis acute	2/4101 (0%)		9/4110 (0.2%)
Pancreatitis haemorrhagic	1/4101 (0%)		0/4110 (0%)
Pancreatolithiasis	1/4101 (0%)		0/4110 (0%)
Peptic ulcer haemorrhage	2/4101 (0%)		0/4110 (0%)
Rectal fissure	1/4101 (0%)		0/4110 (0%)
Rectal haemorrhage	2/4101 (0%)		3/4110 (0.1%)
Rectal polyp	1/4101 (0%)		0/4110 (0%)
Rectal prolapse	0/4101 (0%)		1/4110 (0%)
Small intestinal haemorrhage	0/4101 (0%)		1/4110 (0%)
Small intestinal obstruction	5/4101 (0.1%)		1/4110 (0%)
Subileus	1/4101 (0%)		0/4110 (0%)
Thrombosis mesenteric vessel	1/4101 (0%)		0/4110 (0%)
Tooth disorder	1/4101 (0%)		0/4110 (0%)
Umbilical hernia	0/4101 (0%)		4/4110 (0.1%)
Upper gastrointestinal haemorrhage	9/4101 (0.2%)		10/4110 (0.2%)
Volvulus	1/4101 (0%)		0/4110 (0%)
Vomiting	4/4101 (0.1%)		6/4110 (0.1%)
General disorders
Asthenia	7/4101 (0.2%)		5/4110 (0.1%)
Cardiac death	4/4101 (0.1%)		2/4110 (0%)
Catheter site haemorrhage	0/4101 (0%)		1/4110 (0%)
Chest discomfort	2/4101 (0%)		1/4110 (0%)
Chest pain	22/4101 (0.5%)		15/4110 (0.4%)
Complication associated with device	0/4101 (0%)		3/4110 (0.1%)
Death	49/4101 (1.2%)		65/4110 (1.6%)
Discomfort	1/4101 (0%)		0/4110 (0%)
Drug withdrawal syndrome	0/4101 (0%)		1/4110 (0%)
Fatigue	2/4101 (0%)		2/4110 (0%)
Gait disturbance	1/4101 (0%)		0/4110 (0%)
Gait inability	1/4101 (0%)		0/4110 (0%)
General physical health deterioration	2/4101 (0%)		3/4110 (0.1%)
Generalised oedema	2/4101 (0%)		1/4110 (0%)
Hypothermia	0/4101 (0%)		1/4110 (0%)
Impaired healing	1/4101 (0%)		0/4110 (0%)
Incarcerated hernia	1/4101 (0%)		1/4110 (0%)
Inflammation	0/4101 (0%)		1/4110 (0%)
Influenza like illness	1/4101 (0%)		1/4110 (0%)
Infusion site extravasation	0/4101 (0%)		1/4110 (0%)
Localised oedema	2/4101 (0%)		0/4110 (0%)
Malaise	1/4101 (0%)		0/4110 (0%)
Medical device site haematoma	1/4101 (0%)		1/4110 (0%)
Medical device site haemorrhage	1/4101 (0%)		0/4110 (0%)
Medical device site thrombosis	1/4101 (0%)		0/4110 (0%)
Multiple organ dysfunction syndrome	14/4101 (0.3%)		17/4110 (0.4%)
Nodule	1/4101 (0%)		0/4110 (0%)
Non-cardiac chest pain	27/4101 (0.7%)		33/4110 (0.8%)
Oedema	2/4101 (0%)		2/4110 (0%)
Oedema peripheral	7/4101 (0.2%)		8/4110 (0.2%)
Pacemaker generated arrhythmia	0/4101 (0%)		2/4110 (0%)
Pain	0/4101 (0%)		1/4110 (0%)
Performance status decreased	1/4101 (0%)		0/4110 (0%)
Peripheral swelling	0/4101 (0%)		1/4110 (0%)
Physical deconditioning	0/4101 (0%)		1/4110 (0%)
Pneumatosis	1/4101 (0%)		0/4110 (0%)
Pyrexia	6/4101 (0.1%)		3/4110 (0.1%)
Sudden cardiac death	37/4101 (0.9%)		27/4110 (0.7%)
Sudden death	58/4101 (1.4%)		52/4110 (1.3%)
Swelling face	1/4101 (0%)		0/4110 (0%)
Systemic inflammatory response syndrome	0/4101 (0%)		3/4110 (0.1%)
Ulcer haemorrhage	1/4101 (0%)		1/4110 (0%)
Vascular stent occlusion	0/4101 (0%)		1/4110 (0%)
Vascular stent stenosis	0/4101 (0%)		2/4110 (0%)
Vessel puncture site haemorrhage	0/4101 (0%)		1/4110 (0%)
Hepatobiliary disorders
Acute hepatic failure	2/4101 (0%)		1/4110 (0%)
Alcoholic liver disease	1/4101 (0%)		0/4110 (0%)
Autoimmune hepatitis	0/4101 (0%)		1/4110 (0%)
Bile duct obstruction	1/4101 (0%)		0/4110 (0%)
Bile duct stone	6/4101 (0.1%)		2/4110 (0%)
Biliary colic	1/4101 (0%)		1/4110 (0%)
Cardiac cirrhosis	0/4101 (0%)		1/4110 (0%)
Cholangitis	1/4101 (0%)		6/4110 (0.1%)
Cholangitis acute	0/4101 (0%)		1/4110 (0%)
Cholecystitis	9/4101 (0.2%)		11/4110 (0.3%)
Cholecystitis acute	18/4101 (0.4%)		11/4110 (0.3%)
Cholecystitis chronic	0/4101 (0%)		3/4110 (0.1%)
Cholelithiasis	11/4101 (0.3%)		9/4110 (0.2%)
Cholelithiasis obstructive	1/4101 (0%)		0/4110 (0%)
Cholestasis	1/4101 (0%)		2/4110 (0%)
Cirrhosis alcoholic	1/4101 (0%)		0/4110 (0%)
Congestive hepatopathy	3/4101 (0.1%)		3/4110 (0.1%)
Drug-induced liver injury	2/4101 (0%)		5/4110 (0.1%)
Hepatic cirrhosis	2/4101 (0%)		5/4110 (0.1%)
Hepatic failure	4/4101 (0.1%)		5/4110 (0.1%)
Hepatic function abnormal	3/4101 (0.1%)		3/4110 (0.1%)
Hepatic haematoma	2/4101 (0%)		0/4110 (0%)
Hepatic ischaemia	1/4101 (0%)		0/4110 (0%)
Hepatitis	1/4101 (0%)		1/4110 (0%)
Hepatitis acute	0/4101 (0%)		3/4110 (0.1%)
Hepatocellular injury	0/4101 (0%)		1/4110 (0%)
Hepatorenal failure	1/4101 (0%)		0/4110 (0%)
Hepatorenal syndrome	3/4101 (0.1%)		3/4110 (0.1%)
Hepatotoxicity	3/4101 (0.1%)		0/4110 (0%)
Ischaemic hepatitis	5/4101 (0.1%)		5/4110 (0.1%)
Jaundice	1/4101 (0%)		1/4110 (0%)
Jaundice cholestatic	1/4101 (0%)		0/4110 (0%)
Liver disorder	0/4101 (0%)		1/4110 (0%)
Liver injury	8/4101 (0.2%)		3/4110 (0.1%)
Portal hypertension	1/4101 (0%)		0/4110 (0%)
Portal vein thrombosis	1/4101 (0%)		0/4110 (0%)
Primary biliary cholangitis	1/4101 (0%)		0/4110 (0%)
Venoocclusive liver disease	0/4101 (0%)		1/4110 (0%)
Immune system disorders
Anaphylactic shock	1/4101 (0%)		0/4110 (0%)
Drug hypersensitivity	1/4101 (0%)		2/4110 (0%)
Heart transplant rejection	1/4101 (0%)		0/4110 (0%)
Hypersensitivity	1/4101 (0%)		0/4110 (0%)
Infections and infestations
Abdominal sepsis	1/4101 (0%)		2/4110 (0%)
Abscess jaw	0/4101 (0%)		1/4110 (0%)
Abscess limb	4/4101 (0.1%)		2/4110 (0%)
Acute endocarditis	1/4101 (0%)		1/4110 (0%)
Acute hepatitis B	1/4101 (0%)		0/4110 (0%)
Anal abscess	3/4101 (0.1%)		3/4110 (0.1%)
Appendiceal abscess	0/4101 (0%)		1/4110 (0%)
Appendicitis	3/4101 (0.1%)		4/4110 (0.1%)
Appendicitis perforated	3/4101 (0.1%)		1/4110 (0%)
Arteriosclerotic gangrene	1/4101 (0%)		0/4110 (0%)
Arthritis bacterial	2/4101 (0%)		2/4110 (0%)
Atypical pneumonia	1/4101 (0%)		0/4110 (0%)
Bacteraemia	6/4101 (0.1%)		4/4110 (0.1%)
Bacterial infection	2/4101 (0%)		0/4110 (0%)
Bacterial sepsis	3/4101 (0.1%)		3/4110 (0.1%)
Bacterial tracheitis	1/4101 (0%)		0/4110 (0%)
Biliary sepsis	0/4101 (0%)		3/4110 (0.1%)
Bronchitis	24/4101 (0.6%)		25/4110 (0.6%)
Bronchitis bacterial	1/4101 (0%)		3/4110 (0.1%)
Bronchitis viral	1/4101 (0%)		1/4110 (0%)
Bronchopulmonary aspergillosis	0/4101 (0%)		1/4110 (0%)
Burn infection	2/4101 (0%)		0/4110 (0%)
Bursitis infective staphylococcal	1/4101 (0%)		0/4110 (0%)
COVID-19	3/4101 (0.1%)		8/4110 (0.2%)
COVID-19 pneumonia	3/4101 (0.1%)		7/4110 (0.2%)
Catheter bacteraemia	0/4101 (0%)		1/4110 (0%)
Catheter site infection	0/4101 (0%)		1/4110 (0%)
Cellulitis	24/4101 (0.6%)		34/4110 (0.8%)
Chagas' cardiomyopathy	1/4101 (0%)		0/4110 (0%)
Cholecystitis infective	1/4101 (0%)		1/4110 (0%)
Chronic sinusitis	0/4101 (0%)		1/4110 (0%)
Citrobacter sepsis	1/4101 (0%)		0/4110 (0%)
Clostridial infection	1/4101 (0%)		0/4110 (0%)
Clostridial sepsis	1/4101 (0%)		0/4110 (0%)
Clostridium difficile colitis	1/4101 (0%)		2/4110 (0%)
Clostridium difficile infection	2/4101 (0%)		3/4110 (0.1%)
Complicated appendicitis	1/4101 (0%)		0/4110 (0%)
Conjunctivitis	0/4101 (0%)		1/4110 (0%)
Cystitis	1/4101 (0%)		0/4110 (0%)
Dengue fever	0/4101 (0%)		1/4110 (0%)
Device related infection	5/4101 (0.1%)		3/4110 (0.1%)
Device related sepsis	0/4101 (0%)		1/4110 (0%)
Diabetic foot infection	2/4101 (0%)		6/4110 (0.1%)
Diabetic gangrene	1/4101 (0%)		1/4110 (0%)
Diarrhoea infectious	1/4101 (0%)		0/4110 (0%)
Diverticulitis	2/4101 (0%)		4/4110 (0.1%)
Eczema infected	1/4101 (0%)		0/4110 (0%)
Embolic pneumonia	0/4101 (0%)		1/4110 (0%)
Empyema	0/4101 (0%)		1/4110 (0%)
Encephalitis	1/4101 (0%)		1/4110 (0%)
Endocarditis	7/4101 (0.2%)		3/4110 (0.1%)
Endocarditis bacterial	1/4101 (0%)		2/4110 (0%)
Endocarditis enterococcal	0/4101 (0%)		2/4110 (0%)
Enterobacter bacteraemia	1/4101 (0%)		0/4110 (0%)
Enterococcal bacteraemia	1/4101 (0%)		0/4110 (0%)
Enterococcal infection	1/4101 (0%)		0/4110 (0%)
Enterocolitis bacterial	2/4101 (0%)		0/4110 (0%)
Enterocolitis viral	1/4101 (0%)		0/4110 (0%)
Epididymitis	1/4101 (0%)		0/4110 (0%)
Erysipelas	9/4101 (0.2%)		10/4110 (0.2%)
Escherichia infection	0/4101 (0%)		2/4110 (0%)
Escherichia urinary tract infection	2/4101 (0%)		0/4110 (0%)
Fournier's gangrene	2/4101 (0%)		0/4110 (0%)
Fungal infection	1/4101 (0%)		0/4110 (0%)
Gallbladder abscess	0/4101 (0%)		1/4110 (0%)
Gangrene	8/4101 (0.2%)		5/4110 (0.1%)
Gas gangrene	1/4101 (0%)		0/4110 (0%)
Gastroenteritis	11/4101 (0.3%)		15/4110 (0.4%)
Gastroenteritis bacterial	1/4101 (0%)		2/4110 (0%)
Gastroenteritis norovirus	1/4101 (0%)		0/4110 (0%)
Gastroenteritis viral	2/4101 (0%)		1/4110 (0%)
Gastrointestinal viral infection	0/4101 (0%)		1/4110 (0%)
Graft infection	1/4101 (0%)		1/4110 (0%)
Groin abscess	0/4101 (0%)		1/4110 (0%)
Hepatitis A	1/4101 (0%)		0/4110 (0%)
Hepatitis viral	0/4101 (0%)		1/4110 (0%)
Herpes dermatitis	0/4101 (0%)		1/4110 (0%)
Herpes virus infection	0/4101 (0%)		1/4110 (0%)
Herpes zoster	1/4101 (0%)		1/4110 (0%)
Implant site infection	1/4101 (0%)		3/4110 (0.1%)
Incision site abscess	1/4101 (0%)		0/4110 (0%)
Infected seroma	0/4101 (0%)		1/4110 (0%)
Infected skin ulcer	5/4101 (0.1%)		2/4110 (0%)
Infection	6/4101 (0.1%)		2/4110 (0%)
Infectious pleural effusion	1/4101 (0%)		2/4110 (0%)
Infective exacerbation of chronic obstructive airways disease	3/4101 (0.1%)		4/4110 (0.1%)
Infective myositis	0/4101 (0%)		1/4110 (0%)
Infective spondylitis	0/4101 (0%)		1/4110 (0%)
Influenza	15/4101 (0.4%)		19/4110 (0.5%)
Intervertebral discitis	2/4101 (0%)		0/4110 (0%)
Jejunal gangrene	0/4101 (0%)		1/4110 (0%)
Kidney infection	1/4101 (0%)		0/4110 (0%)
Klebsiella bacteraemia	0/4101 (0%)		1/4110 (0%)
Klebsiella sepsis	0/4101 (0%)		1/4110 (0%)
Labyrinthitis	1/4101 (0%)		2/4110 (0%)
Large intestine infection	1/4101 (0%)		1/4110 (0%)
Laryngitis	0/4101 (0%)		2/4110 (0%)
Liver abscess	0/4101 (0%)		1/4110 (0%)
Localised infection	6/4101 (0.1%)		3/4110 (0.1%)
Lower respiratory tract infection	6/4101 (0.1%)		7/4110 (0.2%)
Lower respiratory tract infection viral	2/4101 (0%)		1/4110 (0%)
Lung abscess	0/4101 (0%)		1/4110 (0%)
Lymphadenitis bacterial	1/4101 (0%)		0/4110 (0%)
Mediastinitis	0/4101 (0%)		1/4110 (0%)
Medical device site infection	3/4101 (0.1%)		0/4110 (0%)
Meningitis bacterial	0/4101 (0%)		1/4110 (0%)
Metapneumovirus infection	1/4101 (0%)		1/4110 (0%)
Myiasis	0/4101 (0%)		1/4110 (0%)
Nasopharyngitis	0/4101 (0%)		1/4110 (0%)
Necrotising fasciitis	1/4101 (0%)		0/4110 (0%)
Ophthalmic herpes zoster	0/4101 (0%)		1/4110 (0%)
Orchitis	0/4101 (0%)		2/4110 (0%)
Osteomyelitis	12/4101 (0.3%)		8/4110 (0.2%)
Osteomyelitis acute	0/4101 (0%)		1/4110 (0%)
Osteomyelitis bacterial	0/4101 (0%)		1/4110 (0%)
Osteomyelitis chronic	1/4101 (0%)		1/4110 (0%)
Otitis media bacterial	0/4101 (0%)		1/4110 (0%)
Parainfluenzae virus infection	1/4101 (0%)		0/4110 (0%)
Peritonitis	5/4101 (0.1%)		0/4110 (0%)
Peritonitis bacterial	0/4101 (0%)		1/4110 (0%)
Peritonsillar abscess	0/4101 (0%)		1/4110 (0%)
Pharyngitis	1/4101 (0%)		1/4110 (0%)
Pilonidal cyst	0/4101 (0%)		1/4110 (0%)
Pneumococcal sepsis	3/4101 (0.1%)		1/4110 (0%)
Pneumonia	179/4101 (4.4%)		171/4110 (4.2%)
Pneumonia adenoviral	1/4101 (0%)		0/4110 (0%)
Pneumonia bacterial	6/4101 (0.1%)		7/4110 (0.2%)
Pneumonia escherichia	0/4101 (0%)		1/4110 (0%)
Pneumonia haemophilus	0/4101 (0%)		1/4110 (0%)
Pneumonia influenzal	2/4101 (0%)		0/4110 (0%)
Pneumonia klebsiella	2/4101 (0%)		1/4110 (0%)
Pneumonia moraxella	1/4101 (0%)		0/4110 (0%)
Pneumonia mycoplasmal	1/4101 (0%)		0/4110 (0%)
Pneumonia necrotising	0/4101 (0%)		1/4110 (0%)
Pneumonia pneumococcal	0/4101 (0%)		1/4110 (0%)
Pneumonia respiratory syncytial viral	0/4101 (0%)		2/4110 (0%)
Pneumonia staphylococcal	0/4101 (0%)		1/4110 (0%)
Pneumonia viral	1/4101 (0%)		1/4110 (0%)
Postoperative wound infection	0/4101 (0%)		2/4110 (0%)
Prostatic abscess	1/4101 (0%)		1/4110 (0%)
Pseudomembranous colitis	1/4101 (0%)		0/4110 (0%)
Pulmonary sepsis	4/4101 (0.1%)		6/4110 (0.1%)
Pulmonary tuberculosis	4/4101 (0.1%)		2/4110 (0%)
Pyelonephritis	5/4101 (0.1%)		2/4110 (0%)
Pyelonephritis acute	4/4101 (0.1%)		3/4110 (0.1%)
Respiratory syncytial virus infection	1/4101 (0%)		1/4110 (0%)
Respiratory tract infection	24/4101 (0.6%)		15/4110 (0.4%)
Respiratory tract infection bacterial	1/4101 (0%)		0/4110 (0%)
Respiratory tract infection fungal	0/4101 (0%)		1/4110 (0%)
Respiratory tract infection viral	2/4101 (0%)		0/4110 (0%)
Scrotal abscess	1/4101 (0%)		0/4110 (0%)
Sepsis	60/4101 (1.5%)		51/4110 (1.2%)
Sepsis syndrome	2/4101 (0%)		0/4110 (0%)
Septic shock	32/4101 (0.8%)		37/4110 (0.9%)
Sinusitis	1/4101 (0%)		0/4110 (0%)
Sinusitis bacterial	0/4101 (0%)		2/4110 (0%)
Skin graft infection	0/4101 (0%)		1/4110 (0%)
Skin infection	1/4101 (0%)		1/4110 (0%)
Soft tissue infection	1/4101 (0%)		4/4110 (0.1%)
Staphylococcal bacteraemia	2/4101 (0%)		3/4110 (0.1%)
Staphylococcal infection	2/4101 (0%)		0/4110 (0%)
Staphylococcal sepsis	5/4101 (0.1%)		2/4110 (0%)
Sternitis	1/4101 (0%)		0/4110 (0%)
Stitch abscess	1/4101 (0%)		0/4110 (0%)
Streptococcal bacteraemia	0/4101 (0%)		1/4110 (0%)
Streptococcal endocarditis	0/4101 (0%)		1/4110 (0%)
Tooth abscess	0/4101 (0%)		1/4110 (0%)
Tooth infection	0/4101 (0%)		1/4110 (0%)
Tracheitis	1/4101 (0%)		0/4110 (0%)
Tracheobronchitis	4/4101 (0.1%)		3/4110 (0.1%)
Tuberculoma of central nervous system	0/4101 (0%)		1/4110 (0%)
Tuberculosis	0/4101 (0%)		1/4110 (0%)
Upper respiratory tract infection	11/4101 (0.3%)		14/4110 (0.3%)
Urinary tract infection	32/4101 (0.8%)		33/4110 (0.8%)
Urinary tract infection bacterial	6/4101 (0.1%)		3/4110 (0.1%)
Urinary tract infection enterococcal	2/4101 (0%)		0/4110 (0%)
Urinary tract infection staphylococcal	1/4101 (0%)		0/4110 (0%)
Urogenital infection bacterial	1/4101 (0%)		0/4110 (0%)
Urosepsis	15/4101 (0.4%)		7/4110 (0.2%)
Vascular device infection	1/4101 (0%)		1/4110 (0%)
Viraemia	1/4101 (0%)		0/4110 (0%)
Viral infection	3/4101 (0.1%)		3/4110 (0.1%)
Viral upper respiratory tract infection	2/4101 (0%)		0/4110 (0%)
Wound abscess	0/4101 (0%)		1/4110 (0%)
Wound infection	5/4101 (0.1%)		1/4110 (0%)
Wound infection bacterial	1/4101 (0%)		0/4110 (0%)
Wound infection staphylococcal	1/4101 (0%)		0/4110 (0%)
Wound sepsis	1/4101 (0%)		2/4110 (0%)
Injury, poisoning and procedural complications
Abdominal wound dehiscence	0/4101 (0%)		1/4110 (0%)
Accidental exposure to product by child	0/4101 (0%)		1/4110 (0%)
Accidental overdose	2/4101 (0%)		1/4110 (0%)
Alcohol poisoning	1/4101 (0%)		1/4110 (0%)
Ankle fracture	5/4101 (0.1%)		4/4110 (0.1%)
Arterial bypass thrombosis	0/4101 (0%)		1/4110 (0%)
Arteriovenous fistula thrombosis	1/4101 (0%)		0/4110 (0%)
Bone contusion	1/4101 (0%)		0/4110 (0%)
Brain contusion	1/4101 (0%)		2/4110 (0%)
Burns third degree	0/4101 (0%)		1/4110 (0%)
Carbon monoxide poisoning	0/4101 (0%)		1/4110 (0%)
Cardiac procedure complication	1/4101 (0%)		0/4110 (0%)
Cardiac vein perforation	1/4101 (0%)		0/4110 (0%)
Cataract traumatic	0/4101 (0%)		1/4110 (0%)
Clavicle fracture	0/4101 (0%)		1/4110 (0%)
Concussion	1/4101 (0%)		1/4110 (0%)
Contusion	3/4101 (0.1%)		3/4110 (0.1%)
Craniocerebral injury	0/4101 (0%)		2/4110 (0%)
Dialysis disequilibrium syndrome	1/4101 (0%)		0/4110 (0%)
Epidural haemorrhage	0/4101 (0%)		1/4110 (0%)
Eschar	1/4101 (0%)		0/4110 (0%)
Facial bones fracture	1/4101 (0%)		0/4110 (0%)
Fall	7/4101 (0.2%)		10/4110 (0.2%)
Femoral neck fracture	8/4101 (0.2%)		8/4110 (0.2%)
Femur fracture	14/4101 (0.3%)		11/4110 (0.3%)
Foot fracture	1/4101 (0%)		1/4110 (0%)
Foreign body in eye	0/4101 (0%)		1/4110 (0%)
Foreign body in gastrointestinal tract	0/4101 (0%)		1/4110 (0%)
Fracture	1/4101 (0%)		0/4110 (0%)
Fracture displacement	1/4101 (0%)		0/4110 (0%)
Fractured coccyx	0/4101 (0%)		1/4110 (0%)
Gastrostomy tube site complication	0/4101 (0%)		1/4110 (0%)
Graft thrombosis	1/4101 (0%)		0/4110 (0%)
Haematuria traumatic	1/4101 (0%)		1/4110 (0%)
Hand fracture	1/4101 (0%)		1/4110 (0%)
Head injury	3/4101 (0.1%)		1/4110 (0%)
Hip fracture	5/4101 (0.1%)		7/4110 (0.2%)
Humerus fracture	4/4101 (0.1%)		6/4110 (0.1%)
Hyphaema	0/4101 (0%)		1/4110 (0%)
Incisional hernia	1/4101 (0%)		0/4110 (0%)
Injury	2/4101 (0%)		3/4110 (0.1%)
Injury corneal	0/4101 (0%)		1/4110 (0%)
Intentional overdose	0/4101 (0%)		1/4110 (0%)
Intestinal anastomosis complication	1/4101 (0%)		0/4110 (0%)
Joint dislocation	0/4101 (0%)		1/4110 (0%)
Joint injury	1/4101 (0%)		0/4110 (0%)
Limb crushing injury	0/4101 (0%)		1/4110 (0%)
Limb injury	1/4101 (0%)		1/4110 (0%)
Limb traumatic amputation	1/4101 (0%)		0/4110 (0%)
Lower limb fracture	1/4101 (0%)		1/4110 (0%)
Lumbar vertebral fracture	1/4101 (0%)		3/4110 (0.1%)
Meniscus injury	0/4101 (0%)		2/4110 (0%)
Multiple fractures	0/4101 (0%)		1/4110 (0%)
Multiple injuries	0/4101 (0%)		3/4110 (0.1%)
Osteophyte fracture	0/4101 (0%)		1/4110 (0%)
Overdose	1/4101 (0%)		1/4110 (0%)
Patella fracture	0/4101 (0%)		2/4110 (0%)
Pelvic fracture	1/4101 (0%)		1/4110 (0%)
Periorbital haemorrhage	0/4101 (0%)		1/4110 (0%)
Pneumocephalus	0/4101 (0%)		1/4110 (0%)
Pneumothorax traumatic	1/4101 (0%)		1/4110 (0%)
Post procedural bile leak	0/4101 (0%)		1/4110 (0%)
Post procedural complication	0/4101 (0%)		3/4110 (0.1%)
Post procedural fever	1/4101 (0%)		0/4110 (0%)
Post procedural haematoma	1/4101 (0%)		1/4110 (0%)
Post procedural haematuria	1/4101 (0%)		1/4110 (0%)
Post procedural haemorrhage	1/4101 (0%)		5/4110 (0.1%)
Post procedural hypotension	0/4101 (0%)		1/4110 (0%)
Postpericardiotomy syndrome	1/4101 (0%)		0/4110 (0%)
Procedural pneumothorax	2/4101 (0%)		1/4110 (0%)
Pulmonary contusion	0/4101 (0%)		1/4110 (0%)
Radius fracture	2/4101 (0%)		2/4110 (0%)
Rib fracture	7/4101 (0.2%)		6/4110 (0.1%)
Road traffic accident	1/4101 (0%)		2/4110 (0%)
Scrotal haematoma	1/4101 (0%)		0/4110 (0%)
Skin laceration	1/4101 (0%)		1/4110 (0%)
Skull fracture	1/4101 (0%)		0/4110 (0%)
Skull fractured base	0/4101 (0%)		1/4110 (0%)
Spinal compression fracture	3/4101 (0.1%)		4/4110 (0.1%)
Spinal fracture	0/4101 (0%)		3/4110 (0.1%)
Subdural haematoma	9/4101 (0.2%)		8/4110 (0.2%)
Subdural haemorrhage	1/4101 (0%)		2/4110 (0%)
Synovial rupture	0/4101 (0%)		1/4110 (0%)
Tendon injury	0/4101 (0%)		1/4110 (0%)
Tendon rupture	1/4101 (0%)		0/4110 (0%)
Thermal burn	2/4101 (0%)		1/4110 (0%)
Thoracic vertebral fracture	1/4101 (0%)		0/4110 (0%)
Tibia fracture	1/4101 (0%)		2/4110 (0%)
Toxicity to various agents	3/4101 (0.1%)		5/4110 (0.1%)
Traumatic haematoma	0/4101 (0%)		1/4110 (0%)
Traumatic intracranial haemorrhage	0/4101 (0%)		2/4110 (0%)
Upper limb fracture	0/4101 (0%)		1/4110 (0%)
Urethral injury	1/4101 (0%)		0/4110 (0%)
Vascular graft complication	0/4101 (0%)		1/4110 (0%)
Vascular graft occlusion	1/4101 (0%)		0/4110 (0%)
Vascular procedure complication	1/4101 (0%)		0/4110 (0%)
Vascular pseudoaneurysm	0/4101 (0%)		2/4110 (0%)
Vasoplegia syndrome	0/4101 (0%)		1/4110 (0%)
Vena cava injury	0/4101 (0%)		1/4110 (0%)
Wound	0/4101 (0%)		2/4110 (0%)
Wound complication	1/4101 (0%)		0/4110 (0%)
Wrist fracture	1/4101 (0%)		1/4110 (0%)
Investigations
Alanine aminotransferase increased	3/4101 (0.1%)		2/4110 (0%)
Anticoagulation drug level above therapeutic	1/4101 (0%)		5/4110 (0.1%)
Anticoagulation drug level below therapeutic	0/4101 (0%)		1/4110 (0%)
Aspartate aminotransferase increased	1/4101 (0%)		1/4110 (0%)
Blood alkaline phosphatase increased	1/4101 (0%)		0/4110 (0%)
Blood calcium decreased	1/4101 (0%)		0/4110 (0%)
Blood creatine phosphokinase increased	1/4101 (0%)		0/4110 (0%)
Blood creatinine increased	1/4101 (0%)		1/4110 (0%)
Blood glucose decreased	1/4101 (0%)		0/4110 (0%)
Blood lactate dehydrogenase increased	0/4101 (0%)		1/4110 (0%)
Blood magnesium decreased	1/4101 (0%)		0/4110 (0%)
Blood potassium decreased	1/4101 (0%)		0/4110 (0%)
Cardiac output decreased	1/4101 (0%)		2/4110 (0%)
Catheterisation cardiac	0/4101 (0%)		1/4110 (0%)
Coagulation time prolonged	1/4101 (0%)		0/4110 (0%)
Ejection fraction decreased	1/4101 (0%)		1/4110 (0%)
Electrocardiogram QT prolonged	1/4101 (0%)		0/4110 (0%)
Electrocardiogram ST segment elevation	0/4101 (0%)		1/4110 (0%)
HIV antibody positive	1/4101 (0%)		0/4110 (0%)
Haemoglobin decreased	0/4101 (0%)		1/4110 (0%)
Hepatic enzyme abnormal	0/4101 (0%)		1/4110 (0%)
Hepatic enzyme increased	6/4101 (0.1%)		4/4110 (0.1%)
Influenza A virus test positive	1/4101 (0%)		1/4110 (0%)
International normalised ratio abnormal	1/4101 (0%)		0/4110 (0%)
International normalised ratio decreased	1/4101 (0%)		0/4110 (0%)
International normalised ratio increased	2/4101 (0%)		3/4110 (0.1%)
Liver function test abnormal	0/4101 (0%)		4/4110 (0.1%)
Liver function test increased	2/4101 (0%)		2/4110 (0%)
Oxygen consumption increased	0/4101 (0%)		1/4110 (0%)
SARS-CoV-2 test positive	1/4101 (0%)		3/4110 (0.1%)
Staphylococcus test positive	1/4101 (0%)		0/4110 (0%)
Transaminases increased	2/4101 (0%)		3/4110 (0.1%)
Transplant evaluation	0/4101 (0%)		1/4110 (0%)
Troponin increased	1/4101 (0%)		3/4110 (0.1%)
Weight decreased	2/4101 (0%)		1/4110 (0%)
Metabolism and nutrition disorders
Abnormal loss of weight	1/4101 (0%)		0/4110 (0%)
Acidosis	1/4101 (0%)		0/4110 (0%)
Cachexia	1/4101 (0%)		2/4110 (0%)
Decreased appetite	0/4101 (0%)		1/4110 (0%)
Dehydration	15/4101 (0.4%)		19/4110 (0.5%)
Diabetes mellitus	8/4101 (0.2%)		15/4110 (0.4%)
Diabetes mellitus inadequate control	5/4101 (0.1%)		6/4110 (0.1%)
Diabetic ketoacidosis	5/4101 (0.1%)		3/4110 (0.1%)
Diabetic ketosis	0/4101 (0%)		1/4110 (0%)
Diabetic metabolic decompensation	8/4101 (0.2%)		1/4110 (0%)
Electrolyte imbalance	1/4101 (0%)		0/4110 (0%)
Failure to thrive	1/4101 (0%)		0/4110 (0%)
Fluid overload	7/4101 (0.2%)		3/4110 (0.1%)
Fluid retention	0/4101 (0%)		1/4110 (0%)
Folate deficiency	0/4101 (0%)		1/4110 (0%)
Gout	7/4101 (0.2%)		14/4110 (0.3%)
Hypercalcaemia	0/4101 (0%)		2/4110 (0%)
Hyperglycaemia	11/4101 (0.3%)		9/4110 (0.2%)
Hyperglycaemic hyperosmolar nonketotic syndrome	2/4101 (0%)		2/4110 (0%)
Hyperkalaemia	21/4101 (0.5%)		20/4110 (0.5%)
Hyperosmolar state	1/4101 (0%)		0/4110 (0%)
Hyperphosphataemia	0/4101 (0%)		1/4110 (0%)
Hypervolaemia	1/4101 (0%)		0/4110 (0%)
Hypoalbuminaemia	1/4101 (0%)		0/4110 (0%)
Hypocalcaemia	1/4101 (0%)		2/4110 (0%)
Hypoglycaemia	13/4101 (0.3%)		7/4110 (0.2%)
Hypokalaemia	13/4101 (0.3%)		7/4110 (0.2%)
Hypokalaemic syndrome	0/4101 (0%)		1/4110 (0%)
Hypomagnesaemia	1/4101 (0%)		1/4110 (0%)
Hyponatraemia	19/4101 (0.5%)		14/4110 (0.3%)
Hypophagia	1/4101 (0%)		0/4110 (0%)
Hypovolaemia	1/4101 (0%)		3/4110 (0.1%)
Lactic acidosis	0/4101 (0%)		1/4110 (0%)
Latent autoimmune diabetes in adults	1/4101 (0%)		0/4110 (0%)
Malnutrition	1/4101 (0%)		1/4110 (0%)
Metabolic acidosis	6/4101 (0.1%)		2/4110 (0%)
Metabolic alkalosis	1/4101 (0%)		0/4110 (0%)
Obesity	2/4101 (0%)		0/4110 (0%)
Type 2 diabetes mellitus	0/4101 (0%)		1/4110 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/4101 (0.1%)		1/4110 (0%)
Arthritis	3/4101 (0.1%)		2/4110 (0%)
Arthritis reactive	0/4101 (0%)		1/4110 (0%)
Arthropathy	2/4101 (0%)		0/4110 (0%)
Back pain	6/4101 (0.1%)		7/4110 (0.2%)
Bursitis	3/4101 (0.1%)		1/4110 (0%)
Compartment syndrome	0/4101 (0%)		1/4110 (0%)
Costochondritis	1/4101 (0%)		1/4110 (0%)
Dupuytren's contracture	1/4101 (0%)		0/4110 (0%)
Elbow deformity	1/4101 (0%)		0/4110 (0%)
Facial asymmetry	1/4101 (0%)		0/4110 (0%)
Fasciitis	0/4101 (0%)		1/4110 (0%)
Flank pain	1/4101 (0%)		0/4110 (0%)
Gouty arthritis	1/4101 (0%)		2/4110 (0%)
Haemarthrosis	0/4101 (0%)		1/4110 (0%)
Haematoma muscle	0/4101 (0%)		2/4110 (0%)
Intervertebral disc compression	0/4101 (0%)		1/4110 (0%)
Intervertebral disc protrusion	4/4101 (0.1%)		1/4110 (0%)
Joint effusion	0/4101 (0%)		1/4110 (0%)
Limb discomfort	1/4101 (0%)		0/4110 (0%)
Lumbar spinal stenosis	0/4101 (0%)		1/4110 (0%)
Mobility decreased	1/4101 (0%)		0/4110 (0%)
Muscle spasms	1/4101 (0%)		0/4110 (0%)
Muscular weakness	0/4101 (0%)		2/4110 (0%)
Musculoskeletal chest pain	4/4101 (0.1%)		10/4110 (0.2%)
Musculoskeletal disorder	1/4101 (0%)		0/4110 (0%)
Musculoskeletal pain	1/4101 (0%)		0/4110 (0%)
Myalgia	1/4101 (0%)		0/4110 (0%)
Myofascial pain syndrome	0/4101 (0%)		1/4110 (0%)
Osteitis	0/4101 (0%)		2/4110 (0%)
Osteoarthritis	9/4101 (0.2%)		12/4110 (0.3%)
Osteochondritis	0/4101 (0%)		2/4110 (0%)
Osteochondrosis	0/4101 (0%)		1/4110 (0%)
Osteolysis	1/4101 (0%)		0/4110 (0%)
Osteonecrosis	1/4101 (0%)		0/4110 (0%)
Osteoporotic fracture	1/4101 (0%)		0/4110 (0%)
Pain in extremity	1/4101 (0%)		2/4110 (0%)
Polyarthritis	1/4101 (0%)		0/4110 (0%)
Polymyalgia rheumatica	1/4101 (0%)		1/4110 (0%)
Pseudarthrosis	0/4101 (0%)		1/4110 (0%)
Rhabdomyolysis	4/4101 (0.1%)		1/4110 (0%)
Rheumatoid arthritis	0/4101 (0%)		1/4110 (0%)
Rotator cuff syndrome	2/4101 (0%)		0/4110 (0%)
Spinal osteoarthritis	1/4101 (0%)		1/4110 (0%)
Spinal pain	4/4101 (0.1%)		0/4110 (0%)
Spondylitis	1/4101 (0%)		0/4110 (0%)
Synovitis	0/4101 (0%)		1/4110 (0%)
Tenosynovitis	1/4101 (0%)		0/4110 (0%)
Vertebral foraminal stenosis	1/4101 (0%)		1/4110 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/4101 (0%)		1/4110 (0%)
Adenocarcinoma gastric	2/4101 (0%)		1/4110 (0%)
Adenocarcinoma of colon	7/4101 (0.2%)		5/4110 (0.1%)
Adenocarcinoma pancreas	1/4101 (0%)		1/4110 (0%)
Adenosquamous cell lung cancer stage III	1/4101 (0%)		0/4110 (0%)
Adrenal adenoma	0/4101 (0%)		1/4110 (0%)
B-cell lymphoma	1/4101 (0%)		0/4110 (0%)
Basal cell carcinoma	1/4101 (0%)		3/4110 (0.1%)
Basosquamous carcinoma	0/4101 (0%)		1/4110 (0%)
Benign neoplasm of testis	0/4101 (0%)		1/4110 (0%)
Bladder adenocarcinoma stage 0	1/4101 (0%)		0/4110 (0%)
Bladder cancer	1/4101 (0%)		2/4110 (0%)
Bladder neoplasm	1/4101 (0%)		0/4110 (0%)
Bladder transitional cell carcinoma	2/4101 (0%)		1/4110 (0%)
Bone sarcoma	1/4101 (0%)		0/4110 (0%)
Cholangiocarcinoma	1/4101 (0%)		0/4110 (0%)
Chronic lymphocytic leukaemia	0/4101 (0%)		1/4110 (0%)
Colon adenoma	0/4101 (0%)		2/4110 (0%)
Colon cancer	7/4101 (0.2%)		4/4110 (0.1%)
Colon cancer metastatic	0/4101 (0%)		1/4110 (0%)
Colorectal cancer	1/4101 (0%)		0/4110 (0%)
Colorectal cancer metastatic	0/4101 (0%)		1/4110 (0%)
Diffuse large B-cell lymphoma	1/4101 (0%)		0/4110 (0%)
Endometrial adenocarcinoma	1/4101 (0%)		0/4110 (0%)
Essential thrombocythaemia	0/4101 (0%)		1/4110 (0%)
Gallbladder cancer metastatic	0/4101 (0%)		1/4110 (0%)
Gastric cancer	1/4101 (0%)		2/4110 (0%)
Gastrointestinal stromal tumour	0/4101 (0%)		1/4110 (0%)
Glioblastoma	2/4101 (0%)		0/4110 (0%)
Glioblastoma multiforme	1/4101 (0%)		0/4110 (0%)
Hepatic cancer	0/4101 (0%)		1/4110 (0%)
Hepatic cancer metastatic	1/4101 (0%)		0/4110 (0%)
Hypopharyngeal cancer	0/4101 (0%)		1/4110 (0%)
Invasive ductal breast carcinoma	1/4101 (0%)		1/4110 (0%)
Keratoacanthoma	0/4101 (0%)		1/4110 (0%)
Laryngeal squamous cell carcinoma	0/4101 (0%)		2/4110 (0%)
Lipoma	0/4101 (0%)		1/4110 (0%)
Liposarcoma	1/4101 (0%)		0/4110 (0%)
Lung adenocarcinoma	1/4101 (0%)		3/4110 (0.1%)
Lung adenocarcinoma stage II	0/4101 (0%)		1/4110 (0%)
Lung cancer metastatic	2/4101 (0%)		2/4110 (0%)
Lung carcinoma cell type unspecified stage III	1/4101 (0%)		2/4110 (0%)
Lung carcinoma cell type unspecified stage IV	2/4101 (0%)		1/4110 (0%)
Lung neoplasm	3/4101 (0.1%)		1/4110 (0%)
Lung neoplasm malignant	5/4101 (0.1%)		6/4110 (0.1%)
Lymphangiosis carcinomatosa	0/4101 (0%)		1/4110 (0%)
Lymphoma	2/4101 (0%)		0/4110 (0%)
Malignant melanoma	1/4101 (0%)		2/4110 (0%)
Malignant neoplasm progression	1/4101 (0%)		0/4110 (0%)
Mediastinum neoplasm	1/4101 (0%)		0/4110 (0%)
Medullary thyroid cancer	1/4101 (0%)		0/4110 (0%)
Melanoma recurrent	0/4101 (0%)		1/4110 (0%)
Metastases to bone	2/4101 (0%)		1/4110 (0%)
Metastases to liver	2/4101 (0%)		1/4110 (0%)
Metastases to lymph nodes	1/4101 (0%)		0/4110 (0%)
Metastases to peritoneum	0/4101 (0%)		1/4110 (0%)
Metastasis	0/4101 (0%)		1/4110 (0%)
Metastatic bronchial carcinoma	1/4101 (0%)		0/4110 (0%)
Metastatic neoplasm	0/4101 (0%)		2/4110 (0%)
Myelodysplastic syndrome	1/4101 (0%)		0/4110 (0%)
Myelofibrosis	0/4101 (0%)		1/4110 (0%)
Nasopharyngeal cancer	1/4101 (0%)		0/4110 (0%)
Neoplasm malignant	2/4101 (0%)		1/4110 (0%)
Neoplasm skin	1/4101 (0%)		0/4110 (0%)
Neuroendocrine carcinoma	0/4101 (0%)		1/4110 (0%)
Neuroendocrine carcinoma of the skin	0/4101 (0%)		1/4110 (0%)
Neuroendocrine tumour of the lung metastatic	1/4101 (0%)		0/4110 (0%)
Non-Hodgkin's lymphoma	1/4101 (0%)		1/4110 (0%)
Non-small cell lung cancer	1/4101 (0%)		0/4110 (0%)
Non-small cell lung cancer stage IV	0/4101 (0%)		2/4110 (0%)
Oesophageal adenocarcinoma	1/4101 (0%)		0/4110 (0%)
Oesophageal carcinoma	1/4101 (0%)		0/4110 (0%)
Oesophageal neoplasm	1/4101 (0%)		0/4110 (0%)
Oesophageal squamous cell carcinoma	1/4101 (0%)		0/4110 (0%)
Oesophageal squamous cell carcinoma stage IV	0/4101 (0%)		1/4110 (0%)
Ovarian cancer	0/4101 (0%)		1/4110 (0%)
Pancreatic carcinoma	1/4101 (0%)		0/4110 (0%)
Pancreatic carcinoma metastatic	2/4101 (0%)		1/4110 (0%)
Pancreatic neoplasm	0/4101 (0%)		1/4110 (0%)
Papillary thyroid cancer	1/4101 (0%)		0/4110 (0%)
Penile cancer	1/4101 (0%)		1/4110 (0%)
Penile squamous cell carcinoma	1/4101 (0%)		0/4110 (0%)
Plasma cell myeloma	1/4101 (0%)		1/4110 (0%)
Prostate cancer	6/4101 (0.1%)		3/4110 (0.1%)
Prostate cancer metastatic	2/4101 (0%)		0/4110 (0%)
Prostate cancer recurrent	1/4101 (0%)		0/4110 (0%)
Prostate cancer stage I	1/4101 (0%)		0/4110 (0%)
Prostate cancer stage IV	0/4101 (0%)		1/4110 (0%)
Prostatic adenoma	1/4101 (0%)		0/4110 (0%)
Rectal adenocarcinoma	0/4101 (0%)		1/4110 (0%)
Rectal cancer	1/4101 (0%)		0/4110 (0%)
Rectal cancer metastatic	1/4101 (0%)		0/4110 (0%)
Rectal neoplasm	1/4101 (0%)		0/4110 (0%)
Renal cancer	1/4101 (0%)		0/4110 (0%)
Renal cell carcinoma	0/4101 (0%)		2/4110 (0%)
Renal neoplasm	0/4101 (0%)		1/4110 (0%)
Small cell lung cancer	2/4101 (0%)		1/4110 (0%)
Small cell lung cancer metastatic	1/4101 (0%)		0/4110 (0%)
Squamous cell carcinoma	2/4101 (0%)		2/4110 (0%)
Squamous cell carcinoma of lung	1/4101 (0%)		1/4110 (0%)
Squamous cell carcinoma of pharynx	1/4101 (0%)		0/4110 (0%)
Squamous cell carcinoma of the cervix	0/4101 (0%)		1/4110 (0%)
Squamous cell carcinoma of the tongue	0/4101 (0%)		1/4110 (0%)
Thyroid adenoma	1/4101 (0%)		0/4110 (0%)
Tonsil cancer	0/4101 (0%)		1/4110 (0%)
Transitional cell carcinoma	3/4101 (0.1%)		2/4110 (0%)
Ureteric cancer	0/4101 (0%)		1/4110 (0%)
Uterine leiomyoma	0/4101 (0%)		1/4110 (0%)
Nervous system disorders
Alcohol induced persisting dementia	0/4101 (0%)		1/4110 (0%)
Altered state of consciousness	1/4101 (0%)		1/4110 (0%)
Amnesia	1/4101 (0%)		0/4110 (0%)
Balance disorder	1/4101 (0%)		0/4110 (0%)
Brain compression	0/4101 (0%)		1/4110 (0%)
Brain hypoxia	0/4101 (0%)		1/4110 (0%)
Brain injury	2/4101 (0%)		2/4110 (0%)
Brain oedema	0/4101 (0%)		2/4110 (0%)
Brain stem stroke	2/4101 (0%)		1/4110 (0%)
Carotid arteriosclerosis	1/4101 (0%)		1/4110 (0%)
Carotid artery disease	0/4101 (0%)		1/4110 (0%)
Carotid artery occlusion	1/4101 (0%)		0/4110 (0%)
Carotid artery stenosis	3/4101 (0.1%)		2/4110 (0%)
Carpal tunnel syndrome	1/4101 (0%)		0/4110 (0%)
Cerebellar haemorrhage	1/4101 (0%)		0/4110 (0%)
Cerebral artery embolism	1/4101 (0%)		0/4110 (0%)
Cerebral circulatory failure	0/4101 (0%)		1/4110 (0%)
Cerebral haematoma	0/4101 (0%)		2/4110 (0%)
Cerebral haemorrhage	7/4101 (0.2%)		2/4110 (0%)
Cerebral hypoperfusion	2/4101 (0%)		0/4110 (0%)
Cerebral infarction	13/4101 (0.3%)		8/4110 (0.2%)
Cerebral ischaemia	4/4101 (0.1%)		3/4110 (0.1%)
Cerebrovascular accident	29/4101 (0.7%)		25/4110 (0.6%)
Cerebrovascular disorder	0/4101 (0%)		2/4110 (0%)
Cerebrovascular insufficiency	1/4101 (0%)		1/4110 (0%)
Cognitive disorder	1/4101 (0%)		1/4110 (0%)
Coma	0/4101 (0%)		1/4110 (0%)
Complex regional pain syndrome	0/4101 (0%)		1/4110 (0%)
Diabetic neuropathy	1/4101 (0%)		2/4110 (0%)
Dizziness	8/4101 (0.2%)		6/4110 (0.1%)
Dizziness postural	3/4101 (0.1%)		0/4110 (0%)
Dysaesthesia	1/4101 (0%)		0/4110 (0%)
Dysarthria	1/4101 (0%)		1/4110 (0%)
Embolic stroke	1/4101 (0%)		2/4110 (0%)
Encephalopathy	2/4101 (0%)		2/4110 (0%)
Epilepsy	2/4101 (0%)		1/4110 (0%)
Generalised tonic-clonic seizure	0/4101 (0%)		1/4110 (0%)
Haemorrhage intracranial	2/4101 (0%)		0/4110 (0%)
Haemorrhagic cerebral infarction	1/4101 (0%)		1/4110 (0%)
Haemorrhagic stroke	7/4101 (0.2%)		3/4110 (0.1%)
Haemorrhagic transformation stroke	1/4101 (0%)		1/4110 (0%)
Headache	4/4101 (0.1%)		1/4110 (0%)
Hemianopia	1/4101 (0%)		1/4110 (0%)
Hemiparesis	1/4101 (0%)		0/4110 (0%)
Hepatic encephalopathy	0/4101 (0%)		2/4110 (0%)
Hydrocephalus	0/4101 (0%)		1/4110 (0%)
Hyperglycaemic unconsciousness	0/4101 (0%)		1/4110 (0%)
Hypoaesthesia	0/4101 (0%)		1/4110 (0%)
Hypoglycaemic unconsciousness	1/4101 (0%)		0/4110 (0%)
Ischaemic cerebral infarction	7/4101 (0.2%)		2/4110 (0%)
Ischaemic stroke	38/4101 (0.9%)		36/4110 (0.9%)
Lacunar infarction	1/4101 (0%)		1/4110 (0%)
Lethargy	0/4101 (0%)		1/4110 (0%)
Loss of consciousness	2/4101 (0%)		2/4110 (0%)
Meningism	1/4101 (0%)		0/4110 (0%)
Metabolic encephalopathy	5/4101 (0.1%)		5/4110 (0.1%)
Mononeuritis	1/4101 (0%)		0/4110 (0%)
Monoplegia	1/4101 (0%)		0/4110 (0%)
Muscle contractions involuntary	0/4101 (0%)		1/4110 (0%)
Myoclonus	0/4101 (0%)		1/4110 (0%)
Neuralgia	1/4101 (0%)		0/4110 (0%)
Neuromyopathy	1/4101 (0%)		1/4110 (0%)
Neuropathy peripheral	1/4101 (0%)		2/4110 (0%)
Normal pressure hydrocephalus	0/4101 (0%)		1/4110 (0%)
Orthostatic intolerance	2/4101 (0%)		0/4110 (0%)
Parkinson's disease	1/4101 (0%)		0/4110 (0%)
Partial seizures	1/4101 (0%)		0/4110 (0%)
Peripheral sensorimotor neuropathy	1/4101 (0%)		0/4110 (0%)
Polyneuropathy	0/4101 (0%)		1/4110 (0%)
Post-traumatic epilepsy	0/4101 (0%)		1/4110 (0%)
Presyncope	5/4101 (0.1%)		8/4110 (0.2%)
Psychogenic seizure	1/4101 (0%)		0/4110 (0%)
Psychomotor disadaptation syndrome	1/4101 (0%)		0/4110 (0%)
Psychomotor hyperactivity	1/4101 (0%)		0/4110 (0%)
Radicular pain	0/4101 (0%)		1/4110 (0%)
Sciatica	1/4101 (0%)		0/4110 (0%)
Sedation	0/4101 (0%)		1/4110 (0%)
Seizure	1/4101 (0%)		2/4110 (0%)
Seizure like phenomena	1/4101 (0%)		0/4110 (0%)
Status epilepticus	0/4101 (0%)		1/4110 (0%)
Stroke in evolution	0/4101 (0%)		1/4110 (0%)
Subarachnoid haemorrhage	6/4101 (0.1%)		3/4110 (0.1%)
Syncope	46/4101 (1.1%)		42/4110 (1%)
Thrombotic stroke	0/4101 (0%)		2/4110 (0%)
Transient ischaemic attack	24/4101 (0.6%)		17/4110 (0.4%)
Trigeminal neuralgia	1/4101 (0%)		0/4110 (0%)
Vertebrobasilar insufficiency	0/4101 (0%)		1/4110 (0%)
Vertigo CNS origin	1/4101 (0%)		0/4110 (0%)
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy	1/4101 (0%)		0/4110 (0%)
Pregnancy	1/4101 (0%)		0/4110 (0%)
Product Issues
Device alarm issue	0/4101 (0%)		1/4110 (0%)
Device dislocation	2/4101 (0%)		0/4110 (0%)
Device electrical impedance issue	1/4101 (0%)		0/4110 (0%)
Device extrusion	1/4101 (0%)		1/4110 (0%)
Device inappropriate shock delivery	1/4101 (0%)		1/4110 (0%)
Device lead damage	1/4101 (0%)		0/4110 (0%)
Device lead issue	1/4101 (0%)		0/4110 (0%)
Device leakage	1/4101 (0%)		0/4110 (0%)
Device malfunction	6/4101 (0.1%)		6/4110 (0.1%)
Device occlusion	0/4101 (0%)		2/4110 (0%)
Device physical property issue	1/4101 (0%)		0/4110 (0%)
Device power source issue	1/4101 (0%)		3/4110 (0.1%)
Device signal detection issue	0/4101 (0%)		1/4110 (0%)
Device stimulation issue	1/4101 (0%)		2/4110 (0%)
Lead dislodgement	0/4101 (0%)		2/4110 (0%)
Oversensing	1/4101 (0%)		0/4110 (0%)
Undersensing	1/4101 (0%)		0/4110 (0%)
Psychiatric disorders
Alcohol abuse	1/4101 (0%)		1/4110 (0%)
Alcohol withdrawal syndrome	1/4101 (0%)		0/4110 (0%)
Alcoholism	0/4101 (0%)		1/4110 (0%)
Anxiety	2/4101 (0%)		1/4110 (0%)
Anxiety disorder	1/4101 (0%)		1/4110 (0%)
Behaviour disorder	1/4101 (0%)		1/4110 (0%)
Bipolar disorder	1/4101 (0%)		0/4110 (0%)
Communication disorder	1/4101 (0%)		0/4110 (0%)
Completed suicide	4/4101 (0.1%)		2/4110 (0%)
Confusional state	1/4101 (0%)		2/4110 (0%)
Conversion disorder	0/4101 (0%)		1/4110 (0%)
Delirium	0/4101 (0%)		1/4110 (0%)
Delusion	1/4101 (0%)		1/4110 (0%)
Depression	4/4101 (0.1%)		2/4110 (0%)
Disorientation	1/4101 (0%)		0/4110 (0%)
Hallucination	1/4101 (0%)		0/4110 (0%)
Major depression	2/4101 (0%)		0/4110 (0%)
Mental disorder	1/4101 (0%)		1/4110 (0%)
Mental status changes	4/4101 (0.1%)		2/4110 (0%)
Panic attack	0/4101 (0%)		1/4110 (0%)
Personality disorder	1/4101 (0%)		0/4110 (0%)
Psychotic behaviour	1/4101 (0%)		0/4110 (0%)
Suicidal ideation	1/4101 (0%)		2/4110 (0%)
Suicide attempt	1/4101 (0%)		1/4110 (0%)
Renal and urinary disorders
Acute kidney injury	138/4101 (3.4%)		129/4110 (3.1%)
Anuria	1/4101 (0%)		1/4110 (0%)
Atonic urinary bladder	0/4101 (0%)		1/4110 (0%)
Azotaemia	0/4101 (0%)		1/4110 (0%)
Bladder neck obstruction	0/4101 (0%)		1/4110 (0%)
Calculus bladder	0/4101 (0%)		1/4110 (0%)
Calculus urinary	0/4101 (0%)		1/4110 (0%)
Chronic kidney disease	36/4101 (0.9%)		36/4110 (0.9%)
Diabetic nephropathy	1/4101 (0%)		0/4110 (0%)
End stage renal disease	4/4101 (0.1%)		7/4110 (0.2%)
Haematinuria	1/4101 (0%)		0/4110 (0%)
Haematuria	7/4101 (0.2%)		3/4110 (0.1%)
Haemorrhage urinary tract	0/4101 (0%)		1/4110 (0%)
Hydronephrosis	2/4101 (0%)		2/4110 (0%)
Hypertensive nephropathy	1/4101 (0%)		0/4110 (0%)
Micturition disorder	1/4101 (0%)		0/4110 (0%)
Nephrolithiasis	5/4101 (0.1%)		1/4110 (0%)
Nephropathy	1/4101 (0%)		2/4110 (0%)
Oliguria	0/4101 (0%)		1/4110 (0%)
Postrenal failure	1/4101 (0%)		3/4110 (0.1%)
Renal arteriosclerosis	0/4101 (0%)		1/4110 (0%)
Renal artery stenosis	0/4101 (0%)		1/4110 (0%)
Renal artery thrombosis	1/4101 (0%)		0/4110 (0%)
Renal colic	0/4101 (0%)		1/4110 (0%)
Renal cyst haemorrhage	0/4101 (0%)		1/4110 (0%)
Renal failure	31/4101 (0.8%)		25/4110 (0.6%)
Renal haemorrhage	0/4101 (0%)		1/4110 (0%)
Renal impairment	29/4101 (0.7%)		25/4110 (0.6%)
Renal infarct	1/4101 (0%)		0/4110 (0%)
Ureterolithiasis	1/4101 (0%)		0/4110 (0%)
Urethral haemorrhage	0/4101 (0%)		1/4110 (0%)
Urethral stenosis	0/4101 (0%)		1/4110 (0%)
Urinary retention	2/4101 (0%)		4/4110 (0.1%)
Urinary tract obstruction	1/4101 (0%)		0/4110 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	5/4101 (0.1%)		5/4110 (0.1%)
Epididymal cyst	1/4101 (0%)		1/4110 (0%)
Metrorrhagia	0/4101 (0%)		1/4110 (0%)
Prostatitis	1/4101 (0%)		1/4110 (0%)
Prostatomegaly	0/4101 (0%)		1/4110 (0%)
Scrotal oedema	2/4101 (0%)		0/4110 (0%)
Spermatocele	1/4101 (0%)		0/4110 (0%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	10/4101 (0.2%)		10/4110 (0.2%)
Acute respiratory distress syndrome	2/4101 (0%)		2/4110 (0%)
Acute respiratory failure	18/4101 (0.4%)		20/4110 (0.5%)
Aspiration	3/4101 (0.1%)		1/4110 (0%)
Asthma	6/4101 (0.1%)		2/4110 (0%)
Asthma-chronic obstructive pulmonary disease overlap syndrome	1/4101 (0%)		0/4110 (0%)
Bronchial disorder	0/4101 (0%)		1/4110 (0%)
Bronchiectasis	1/4101 (0%)		0/4110 (0%)
Bronchitis chronic	0/4101 (0%)		1/4110 (0%)
Bronchopneumopathy	1/4101 (0%)		0/4110 (0%)
Bronchospasm	2/4101 (0%)		1/4110 (0%)
Chronic obstructive pulmonary disease	38/4101 (0.9%)		63/4110 (1.5%)
Chronic respiratory disease	0/4101 (0%)		1/4110 (0%)
Cystic lung disease	0/4101 (0%)		1/4110 (0%)
Dyspnoea	31/4101 (0.8%)		28/4110 (0.7%)
Dyspnoea at rest	2/4101 (0%)		1/4110 (0%)
Dyspnoea exertional	1/4101 (0%)		2/4110 (0%)
Epistaxis	5/4101 (0.1%)		5/4110 (0.1%)
Haemoptysis	4/4101 (0.1%)		3/4110 (0.1%)
Haemothorax	0/4101 (0%)		1/4110 (0%)
Hydrothorax	0/4101 (0%)		1/4110 (0%)
Hypercapnia	2/4101 (0%)		0/4110 (0%)
Hypoxia	1/4101 (0%)		0/4110 (0%)
Idiopathic pulmonary fibrosis	0/4101 (0%)		1/4110 (0%)
Interstitial lung disease	5/4101 (0.1%)		1/4110 (0%)
Lung consolidation	0/4101 (0%)		1/4110 (0%)
Lung disorder	2/4101 (0%)		3/4110 (0.1%)
Lung infiltration	1/4101 (0%)		0/4110 (0%)
Nasal polyps	0/4101 (0%)		1/4110 (0%)
Paranasal cyst	0/4101 (0%)		1/4110 (0%)
Pleural disorder	0/4101 (0%)		1/4110 (0%)
Pleural effusion	14/4101 (0.3%)		11/4110 (0.3%)
Pneumonia aspiration	6/4101 (0.1%)		6/4110 (0.1%)
Pneumonitis	2/4101 (0%)		4/4110 (0.1%)
Pneumothorax	1/4101 (0%)		2/4110 (0%)
Pneumothorax spontaneous	1/4101 (0%)		0/4110 (0%)
Pulmonary arterial hypertension	1/4101 (0%)		1/4110 (0%)
Pulmonary artery thrombosis	0/4101 (0%)		2/4110 (0%)
Pulmonary congestion	3/4101 (0.1%)		0/4110 (0%)
Pulmonary embolism	13/4101 (0.3%)		20/4110 (0.5%)
Pulmonary haemorrhage	1/4101 (0%)		2/4110 (0%)
Pulmonary hypertension	1/4101 (0%)		2/4110 (0%)
Pulmonary mass	1/4101 (0%)		1/4110 (0%)
Pulmonary oedema	12/4101 (0.3%)		14/4110 (0.3%)
Pulmonary vascular disorder	0/4101 (0%)		1/4110 (0%)
Respiratory acidosis	0/4101 (0%)		1/4110 (0%)
Respiratory arrest	2/4101 (0%)		3/4110 (0.1%)
Respiratory disorder	1/4101 (0%)		0/4110 (0%)
Respiratory failure	18/4101 (0.4%)		22/4110 (0.5%)
Sleep apnoea syndrome	1/4101 (0%)		2/4110 (0%)
Stridor	0/4101 (0%)		1/4110 (0%)
Tonsillar hypertrophy	0/4101 (0%)		1/4110 (0%)
Tracheal stenosis	0/4101 (0%)		1/4110 (0%)
Tracheomalacia	1/4101 (0%)		0/4110 (0%)
Skin and subcutaneous tissue disorders
Angioedema	0/4101 (0%)		1/4110 (0%)
Blister	0/4101 (0%)		1/4110 (0%)
Decubitus ulcer	2/4101 (0%)		1/4110 (0%)
Dermal cyst	1/4101 (0%)		0/4110 (0%)
Dermatitis exfoliative	1/4101 (0%)		0/4110 (0%)
Dermatitis exfoliative generalised	1/4101 (0%)		0/4110 (0%)
Diabetic foot	6/4101 (0.1%)		4/4110 (0.1%)
Diabetic ulcer	1/4101 (0%)		1/4110 (0%)
Drug eruption	0/4101 (0%)		1/4110 (0%)
Hair growth abnormal	1/4101 (0%)		0/4110 (0%)
Hyperhidrosis	0/4101 (0%)		1/4110 (0%)
Peau d'orange	0/4101 (0%)		1/4110 (0%)
Pemphigoid	0/4101 (0%)		1/4110 (0%)
Pruritus	1/4101 (0%)		2/4110 (0%)
Psoriasis	1/4101 (0%)		1/4110 (0%)
Rash	1/4101 (0%)		1/4110 (0%)
Skin erosion	1/4101 (0%)		0/4110 (0%)
Skin lesion	1/4101 (0%)		0/4110 (0%)
Skin necrosis	1/4101 (0%)		0/4110 (0%)
Skin ulcer	7/4101 (0.2%)		6/4110 (0.1%)
Stasis dermatitis	1/4101 (0%)		1/4110 (0%)
Toxic skin eruption	1/4101 (0%)		0/4110 (0%)
Social circumstances
Physical assault	0/4101 (0%)		1/4110 (0%)
Victim of homicide	1/4101 (0%)		0/4110 (0%)
Surgical and medical procedures
Appendicectomy	0/4101 (0%)		1/4110 (0%)
Arrhythmia prophylaxis	0/4101 (0%)		1/4110 (0%)
Bladder catheter replacement	1/4101 (0%)		0/4110 (0%)
Cardiac pacemaker replacement	0/4101 (0%)		1/4110 (0%)
Cardiac resynchronisation therapy	1/4101 (0%)		3/4110 (0.1%)
Coronary angioplasty	0/4101 (0%)		1/4110 (0%)
Coronary artery bypass	0/4101 (0%)		1/4110 (0%)
Coronary revascularisation	2/4101 (0%)		2/4110 (0%)
Heart transplant	2/4101 (0%)		2/4110 (0%)
Hernia diaphragmatic repair	0/4101 (0%)		1/4110 (0%)
Hip arthroplasty	0/4101 (0%)		1/4110 (0%)
Hospitalisation	2/4101 (0%)		0/4110 (0%)
Implantable defibrillator insertion	2/4101 (0%)		0/4110 (0%)
Implantable defibrillator removal	1/4101 (0%)		0/4110 (0%)
Inguinal hernia repair	1/4101 (0%)		0/4110 (0%)
Knee arthroplasty	1/4101 (0%)		0/4110 (0%)
Percutaneous coronary intervention	2/4101 (0%)		0/4110 (0%)
Preoperative care	0/4101 (0%)		1/4110 (0%)
Toe amputation	2/4101 (0%)		1/4110 (0%)
Transurethral prostatectomy	1/4101 (0%)		0/4110 (0%)
Vascular disorders
Aortic aneurysm	5/4101 (0.1%)		1/4110 (0%)
Aortic aneurysm rupture	0/4101 (0%)		2/4110 (0%)
Aortic dissection	1/4101 (0%)		0/4110 (0%)
Aortic dissection rupture	1/4101 (0%)		0/4110 (0%)
Aortic rupture	0/4101 (0%)		1/4110 (0%)
Aortic stenosis	4/4101 (0.1%)		1/4110 (0%)
Arterial disorder	0/4101 (0%)		2/4110 (0%)
Arterial haemorrhage	0/4101 (0%)		1/4110 (0%)
Arterial occlusive disease	1/4101 (0%)		0/4110 (0%)
Arterial perforation	1/4101 (0%)		0/4110 (0%)
Arterial stenosis	1/4101 (0%)		0/4110 (0%)
Arteriosclerosis	2/4101 (0%)		4/4110 (0.1%)
Axillary vein thrombosis	1/4101 (0%)		0/4110 (0%)
Brachiocephalic vein thrombosis	0/4101 (0%)		1/4110 (0%)
Deep vein thrombosis	7/4101 (0.2%)		0/4110 (0%)
Diabetic macroangiopathy	0/4101 (0%)		1/4110 (0%)
Distributive shock	1/4101 (0%)		0/4110 (0%)
Dry gangrene	0/4101 (0%)		1/4110 (0%)
Embolism arterial	0/4101 (0%)		3/4110 (0.1%)
Extremity necrosis	3/4101 (0.1%)		3/4110 (0.1%)
Haematoma	4/4101 (0.1%)		2/4110 (0%)
Haemodynamic instability	1/4101 (0%)		0/4110 (0%)
Hypertension	10/4101 (0.2%)		9/4110 (0.2%)
Hypertensive crisis	5/4101 (0.1%)		3/4110 (0.1%)
Hypertensive emergency	2/4101 (0%)		1/4110 (0%)
Hypertensive urgency	1/4101 (0%)		4/4110 (0.1%)
Hypoperfusion	0/4101 (0%)		2/4110 (0%)
Hypotension	37/4101 (0.9%)		49/4110 (1.2%)
Hypovolaemic shock	4/4101 (0.1%)		5/4110 (0.1%)
Iliac artery stenosis	0/4101 (0%)		1/4110 (0%)
Infarction	1/4101 (0%)		0/4110 (0%)
Ischaemia	1/4101 (0%)		0/4110 (0%)
Jugular vein thrombosis	0/4101 (0%)		1/4110 (0%)
Leriche syndrome	1/4101 (0%)		0/4110 (0%)
Malignant hypertension	1/4101 (0%)		0/4110 (0%)
Orthostatic hypertension	0/4101 (0%)		1/4110 (0%)
Orthostatic hypotension	11/4101 (0.3%)		12/4110 (0.3%)
Pelvic venous thrombosis	1/4101 (0%)		0/4110 (0%)
Peripheral arterial occlusive disease	18/4101 (0.4%)		17/4110 (0.4%)
Peripheral artery occlusion	5/4101 (0.1%)		2/4110 (0%)
Peripheral artery stenosis	2/4101 (0%)		2/4110 (0%)
Peripheral artery thrombosis	2/4101 (0%)		6/4110 (0.1%)
Peripheral ischaemia	14/4101 (0.3%)		9/4110 (0.2%)
Peripheral vascular disorder	3/4101 (0.1%)		1/4110 (0%)
Peripheral venous disease	0/4101 (0%)		1/4110 (0%)
Phlebitis	0/4101 (0%)		1/4110 (0%)
Post thrombotic syndrome	1/4101 (0%)		0/4110 (0%)
Shock	1/4101 (0%)		1/4110 (0%)
Shock haemorrhagic	1/4101 (0%)		1/4110 (0%)
Thrombophlebitis	0/4101 (0%)		1/4110 (0%)
Thrombophlebitis superficial	1/4101 (0%)		0/4110 (0%)
Varicose vein ruptured	1/4101 (0%)		0/4110 (0%)
Vasculitis	0/4101 (0%)		1/4110 (0%)
Venous thrombosis limb	2/4101 (0%)		4/4110 (0.1%)
Other (Not Including Serious) Adverse Events
	Placebo		Omecamtiv Mecarbil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1146/4101 (27.9%)		1129/4110 (27.5%)
Cardiac disorders
Cardiac failure	291/4101 (7.1%)		268/4110 (6.5%)
Metabolism and nutrition disorders
Hyperkalaemia	213/4101 (5.2%)		202/4110 (4.9%)
Nervous system disorders
Dizziness	183/4101 (4.5%)		232/4110 (5.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	258/4101 (6.3%)		249/4110 (6.1%)
Vascular disorders
Hypertension	222/4101 (5.4%)		190/4110 (4.6%)
Hypotension	242/4101 (5.9%)		276/4110 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.