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CREDENCE: Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT02065791
Collaborator
The George Institute for Global Health, Australia (Other)
4,401
Enrollment
593
Locations
2
Arms
56.4
Actual Duration (Months)
7.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this study is to assess whether canagliflozin has a renal and vascular protective effect in reducing the progression of renal impairment relative to placebo in participants with type 2 diabetes mellitus (T2DM), Stage 2 or 3 chronic kidney disease (CKD) and macroalbuminuria, who are receiving standard of care including a maximum tolerated labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB).

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), placebo-controlled (an inactive substance that is compared with a medication to test whether the medication has a real effect), parallel-group, multicenter study of the effects of canagliflozin on renal and cardiovascular outcomes in participants with type 2 diabetes mellitus (T2DM) and diabetic nephropathy, who are receiving standard of care including a maximum tolerated daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB).

The study will consist of a pretreatment phase (several weeks), and a double-blind treatment phase (up to approximately 66 months). During the pretreatment phase all participants will also receive diet/exercise counseling for lipid and blood pressure management as well as counseling on renal and cardiovascular (CV) risk factor medication. A post-treatment follow-up contact or visit will take place approximately 30 days after the last dose of study drug or the completion of the study. The total duration of the study is estimated to be about 5 to 5.5 years. Approximately 4,200 participants will be randomized in a 1:1 ratio to canagliflozin or matching placebo. Participants randomized to canagliflozin will receive a dose of 100 mg once daily. The overall safety and tolerability of canagliflozin will be evaluated by collecting information on adverse events, laboratory tests, vital signs (pulse, blood pressure), physical examination, and body weight.

Study Design

Study Type:
Interventional
Actual Enrollment :
4401 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Event-driven, Placebo-controlled, Multicenter Study of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Subjects With Type 2 Diabetes Mellitus and Diabetic Nephropathy
Actual Study Start Date :
Feb 17, 2014
Actual Primary Completion Date :
Oct 30, 2018
Actual Study Completion Date :
Oct 30, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Canagliflozin 100 mg

Each participant will receive 100 mg of canagliflozin once daily

Drug: Canagliflozin
One 100 mg over-encapsulated tablet orally once daily
Placebo Comparator: Placebo

Each participant will receive matching placebo once daily

Drug: Placebo
One matching placebo capsule orally (by mouth) once daily

Outcome Measures

Primary Outcome Measures

  1. Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (ESKD), and Renal or Cardiovascular (CV) Death [Up to 4.6 years]

    Primary composite endpoint is the composite of DoSC, ESKD, and renal or CV death. DoSC: from baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). ESKD: as initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an estimated glomerular filtration rate (eGFR) value of less than (<)15 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who had reached ESKD, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by Endpoint Adjudication Committee (EAC) was performed in blinded fashion. Event rate estimated based on time to first occurrence of primary composite endpoint are presented.

Secondary Outcome Measures

  1. Composite Endpoint of CV Death and Hospitalized Heart Failure (HHF) [Up to 4.6 years]

    The composite endpoint included CV death and HHF. CV death included death due to myocardial infarction (MI), stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the composite endpoint of CV death and HHF are presented.

  2. Major Adverse Cardiac Event (MACE) [Up to 4.6 years]

    The composite endpoint included CV death, non-fatal MI, and non-fatal stroke (that is, 3-point MACE). Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of MACE are presented.

  3. Hospitalized Heart Failure (HHF) [Up to 4.6 years]

    Adjudication of these events by the Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of hospitalized heart failure are presented.

  4. Renal Composite Endpoint [Up to 4.6 years]

    The renal composite endpoint included composite of DoSC, ESKD and Renal death. DoSC: from the baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). ESKD: initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an eGFR value of <15 mL/min/1.73 m^2 (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who have reached ESKD, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the renal composite endpoint are presented.

  5. Cardiovascular (CV) Death [Up to 4.6 years]

    CV death included death due to MI, stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was a CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of CV death are presented.

  6. All-cause Mortality [Up to 4.6 years]

    Adjudication of these events by Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on time to first occurrence of all-cause mortality are presented.

  7. CV Composite Endpoint [Up to 4.6 years]

    The CV composite endpoint included the CV death, non-fatal MI, non-fatal stroke, hospitalized heart failure, and hospitalized unstable angina. CV death included death due to MI, stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was a CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the CV composite endpoint are presented.

Eligibility Criteria

Criteria

Ages Eligible for Study:
30 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Type 2 diabetes mellitus with a hemoglobin A1c (HbA1c) greater than or equal to (>=) 6.5 percent (%) and less than or equal to (<=) 12.0%, with an estimated glomerular filtration rate (eGFR) of >= 30 milliliter (mL)/minute (min)/1.73meter (m)2 and less than (<) 90 mL/min/1.73 m2

  • Participants need to be on a stable maximum tolerated labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for at least 4 weeks prior to randomization

  • Must have a urine albumin to creatinine ratio (UACR) of greater than (>) 300 milligram (mg)/gram (g) and <= 5000 mg/g

Exclusion Criteria:

  • History of diabetic ketoacidosis or type 1 diabetes mellitus

  • History of hereditary glucose-galactose malabsorption or primary renal glucosuria

  • Renal disease that required treatment with immunosuppressive therapy

  • Known significant liver disease

  • Current or history of New York Heart Association (NYHA) Class IV heart failure

  • Blood potassium level >5.5 millimole (mmol)/liter (L) during Screening

Contacts and Locations

Locations

Site City State Country Postal Code
1 Birmingham Alabama United States
2 Montgomery Alabama United States
3 Tempe Arizona United States
4 Tucson Arizona United States
5 Little Rock Arkansas United States
6 Sherwood Arkansas United States
7 Bakersfield California United States
8 Chula Vista California United States
9 Covina California United States
10 Downey California United States
11 Fountain Valley California United States
12 Hawthorne California United States
13 Inglewood California United States
14 Laguna Hills California United States
15 Lakewood California United States
16 Long Beach California United States
17 Los Angeles California United States
18 Lynwood California United States
19 Northridge California United States
20 Oakland California United States
21 Orange California United States
22 Pasadena California United States
23 Roseville California United States
24 Sacramento California United States
25 Salinas California United States
26 San Diego California United States
27 San Dimas California United States
28 Stanford California United States
29 Tustin California United States
30 Whittier California United States
31 Denver Colorado United States
32 Golden Colorado United States
33 Lakewood Colorado United States
34 Washington Colorado United States
35 Washington District of Columbia United States
36 Coral Springs Florida United States
37 Doral Florida United States
38 Hialeah Florida United States
39 Jacksonville Florida United States
40 Miami Springs Florida United States
41 Miami Florida United States
42 North Miami Beach Florida United States
43 Ocala Florida United States
44 Port Charlotte Florida United States
45 Saint Petersburg Florida United States
46 Winter Park Florida United States
47 Atlanta Georgia United States
48 Augusta Georgia United States
49 Columbus Georgia United States
50 Roswell Georgia United States
51 Snellville Georgia United States
52 Stockbridge Georgia United States
53 Chicago Illinois United States
54 Crystal Lake Illinois United States
55 Gurnee Illinois United States
56 Mount Prospect Illinois United States
57 Winfield Illinois United States
58 Fort Wayne Indiana United States
59 Indianapolis Indiana United States
60 Merrillville Indiana United States
61 Michigan City Indiana United States
62 Muncie Indiana United States
63 Council Bluffs Iowa United States
64 Louisville Kentucky United States
65 Paducah Kentucky United States
66 Kenner Louisiana United States
67 Rockport Maine United States
68 Scarborough Maine United States
69 Annapolis Maryland United States
70 Baltimore Maryland United States
71 Beltsville Maryland United States
72 Hyattsville Maryland United States
73 Silver Spring Maryland United States
74 Boston Massachusetts United States
75 Plymouth Massachusetts United States
76 Springfield Massachusetts United States
77 Worcester Massachusetts United States
78 Flint Michigan United States
79 Jackson Mississippi United States
80 Chesterfield Missouri United States
81 Kansas City Missouri United States
82 Saint Louis Missouri United States
83 Fremont Nebraska United States
84 Lincoln Nebraska United States
85 Omaha Nebraska United States
86 Reno Nebraska United States
87 Las Vegas Nevada United States
88 Eatontown New Jersey United States
89 Albuquerque New Mexico United States
90 Albany New York United States
91 Binghamton New York United States
92 Buffalo New York United States
93 Great Neck New York United States
94 Lake Success New York United States
95 New Hyde Park New York United States
96 New York New York United States
97 Ridgewood New York United States
98 Riverhead New York United States
99 Smithtown New York United States
100 Springfield Gardens New York United States
101 Asheville North Carolina United States
102 Calabash North Carolina United States
103 Charlotte North Carolina United States
104 Durham North Carolina United States
105 Greensboro North Carolina United States
106 Greenville North Carolina United States
107 High Point North Carolina United States
108 Morehead City North Carolina United States
109 Morganton North Carolina United States
110 Raleigh North Carolina United States
111 Tabor City North Carolina United States
112 Whiteville North Carolina United States
113 Cincinnati Ohio United States
114 Columbus Ohio United States
115 Maumee Ohio United States
116 Roseburg Oregon United States
117 Beaver Pennsylvania United States
118 Bethlehem Pennsylvania United States
119 Philadelphia Pennsylvania United States
120 Pittsburgh Pennsylvania United States
121 Anderson South Carolina United States
122 Columbia South Carolina United States
123 Lancaster South Carolina United States
124 Murrells Inlet South Carolina United States
125 Orangeburg South Carolina United States
126 Sumter South Carolina United States
127 Chattanooga Tennessee United States
128 Knoxville Tennessee United States
129 Memphis Tennessee United States
130 Arlington Texas United States
131 Corpus Christi Texas United States
132 Corsicana Texas United States
133 Dallas Texas United States
134 Edinburg Texas United States
135 Fort Worth Texas United States
136 Houston Texas United States
137 Mesquite Texas United States
138 San Antonio Texas United States
139 Schertz Texas United States
140 Sugar Land Texas United States
141 Temple Texas United States
142 Waco Texas United States
143 Salt Lake City Utah United States
144 Bennington Vermont United States
145 Burlington Vermont United States
146 Bluefield Virginia United States
147 Mechanicsville Virginia United States
148 Norfolk Virginia United States
149 Suffolk Virginia United States
150 Spokane Washington United States
151 Huntington West Virginia United States
152 Milwaukee Wisconsin United States
153 Bahia Blanca Argentina
154 Buenos Aires Argentina
155 Ciudad Autonoma Buenos Aires Argentina
156 Cordoba Argentina
157 Corrientes Argentina
158 Córdoba Argentina
159 Godoy Cruz Argentina
160 Junin Argentina
161 La Plata Lpl Lpl Argentina
162 La Plata Argentina
163 Mar del Plata Argentina
164 Mendoza Argentina
165 Moron Argentina
166 Munro Argentina
167 Parana Argentina
168 Quilmes Argentina
169 Ramos Mejia Argentina
170 Rosario Argentina
171 Salta Argentina
172 San Luis Argentina
173 San Martin Argentina
174 San Migeul De Tucuman Argentina
175 San Miguel de Tucuman Argentina
176 San Nicolas Argentina
177 Santa Fe Argentina
178 Sarandi Argentina
179 Tapiales Argentina
180 Temperley Argentina
181 Villa Maria Argentina
182 Zarate, Buenos Aires Argentina
183 Cairns Australia
184 Concord Australia
185 Darlinghurst Australia
186 Elizabeth Vale Australia
187 Fremantle Australia
188 Gosford Australia
189 Heidelberg Australia
190 Keswick Australia
191 Meadowbrook Australia
192 Parkville Australia
193 Reservoir Australia
194 Richmond Australia
195 St Albans Australia
196 St Leonards Australia
197 Sydney Australia
198 Woolloongabba Australia
199 Aparecida de Goiânia Brazil
200 Belo Horizonte Brazil
201 Belém Brazil
202 Botucatu Brazil
203 Brasilia Brazil
204 Campina Grande Do Sul Brazil
205 Campinas Brazil
206 Canoas Brazil
207 Caxias do Sul Brazil
208 Curitiba Brazil
209 Fortaleza Brazil
210 Joinville Brazil
211 Juiz de Fora Brazil
212 Maringá Brazil
213 Passo Fundo Brazil
214 Porto Alegre Brazil
215 Rio de Janeiro Brazil
216 Santo Andre Brazil
217 Santo André Brazil
218 Sao Jose Do Rio Preto Brazil
219 Sao Paulo Brazil
220 São José dos Campos Brazil
221 São Paulo Brazil
222 Tatuí Brazil
223 Blagoevgrad Bulgaria
224 Byala Bulgaria
225 Gulyantsi Bulgaria
226 Pazardzhik Bulgaria
227 Pleven Bulgaria
228 Plovdiv Bulgaria
229 Sofia Bulgaria
230 Varna Bulgaria
231 Edmonton Alberta Canada
232 New Westminster British Columbia Canada
233 Vancouver British Columbia Canada
234 Winnipeg Manitoba Canada
235 Brampton Ontario Canada
236 London Ontario Canada
237 NewMarket Ontario Canada
238 Oshawa Ontario Canada
239 Smiths Falls Ontario Canada
240 Thornhill Ontario Canada
241 Toronto Ontario Canada
242 Weston Ontario Canada
243 Greenfield Park Quebec Canada
244 Montreal Quebec Canada
245 Québec Quebec Canada
246 Quebec Canada
247 Québec Canada
248 Toronto Canada
249 Vancouver Canada
250 Concepcion Chile
251 Santiago Chile
252 Temuco Chile
253 Beijing China
254 Changchun China
255 Changde China
256 Changsha China
257 Chengdu China
258 Chenzhou China
259 Dalian China
260 Foshan China
261 Guangzhou China
262 Huai'an China
263 Nanchang China
264 Nanjing China
265 Shanghai China
266 Shenyang China
267 Wuhan China
268 Wulumuqi China
269 Xian China
270 Barranquilla Colombia
271 Bogota Colombia
272 Bucaramanga Colombia
273 Cali Colombia
274 Floridablanca Colombia
275 Manizales Colombia
276 Medellin Colombia
277 Pasto Colombia
278 Pereira Colombia
279 Ceske Budejovice Czechia
280 Cesky Krumlov Czechia
281 Chocen Czechia
282 Havlickuv Brod Czechia
283 Hradec Kralove-Vekose Czechia
284 Hradec Nad Svitavou Czechia
285 Jindrichuv Hradec Czechia
286 Olomouc Czechia
287 Praha 10 Czechia
288 Praha 2 Czechia
289 Praha 4 Czechia
290 Praha 5 Czechia
291 Praha Czechia
292 Slany Czechia
293 Trutnov Czechia
294 Uherske Hradiste Czechia
295 Usti Nad Labem Czechia
296 Besancon Cedex France
297 Brest cedex France
298 Colmar N/a France
299 Corbeil Essonnes Cedex France
300 Créteil Cedex France
301 Grenoble France
302 Lyon cedex 03 France
303 Marseille Cedex 05 France
304 Metz cedex 03 France
305 Nantes Cedex 01 France
306 Paris Cedex 15 France
307 Paris Cedex 18 France
308 Paris France
309 Pierre-Bénit France
310 Poitiers France
311 St Priest-en-Jarez France
312 Strasbourg France
313 Toulouse Cedex 9 France
314 Bad Kreuznach - Bosenheim Germany
315 Dietzenbach Germany
316 Dresden Germany
317 Essen Germany
318 Hamburg Germany
319 Hannover Germany
320 Köln Germany
321 Muenster Germany
322 Guatemala City Guatemala
323 Guatemala Guatemala
324 Baja Hungary
325 Balatonfured Hungary
326 Budapest Hungary
327 Debrecen Hungary
328 Eger Hungary
329 Esztergom Hungary
330 Godollo Hungary
331 Gyula Hungary
332 Hu-4012 Debrecen N/a Hungary
333 Kaposvar Hungary
334 Kecskemet N/a Hungary
335 Komarom Hungary
336 Nyiregyhaza Hungary
337 Pecs Hungary
338 Szeged N/a Hungary
339 Szigetvar Hungary
340 Veszprem Hungary
341 Zalaegerszeg Hungary
342 Calicut India
343 Chennai India
344 Delhi India
345 Hyderabad India
346 Kozhikode India
347 Lucknow India
348 Ludhiyana India
349 Mangalore India
350 Mumbai India
351 Mysore India
352 Secunderabad India
353 Trivandrum India
354 Vijayawada India
355 Vishakhapatnam India
356 Ageo-shi Japan
357 Chiyoda-ku Japan
358 Fukuoka Japan
359 Hamamatsu-shi Japan
360 Hamura-shi Japan
361 Ina-shi Japan
362 Izumisano Japan
363 Kamakura-shi Japan
364 Kanazawa Japan
365 Kawanishi-shi Japan
366 Koriyama-shi Japan
367 Kuki-shi Japan
368 Kyoto Japan
369 Matsuyama-shi Japan
370 Midori-shi Japan
371 Minato-ku Japan
372 Nagoya-shi Japan
373 Osaka-shi Japan
374 Ota-shi Japan
375 Saiki-shi Japan
376 Sashima-gun Japan
377 Shinjuku-ku Japan
378 Toyama-shi Japan
379 Uwajima-shi Japan
380 Yamanashi Japan
381 Yokohama-City Japan
382 Yokohama-shi Japan
383 Busan Korea, Republic of
384 Daegu Korea, Republic of
385 Incheon Korea, Republic of
386 Seongnam Korea, Republic of
387 Seoul Korea, Republic of
388 Kaunas Lithuania
389 Klaipeda Lithuania
390 Siauliai Lithuania
391 Batu Caves Malaysia
392 Ipoh Malaysia
393 Johor Malaysia
394 Kuala Lumpur N/a Malaysia
395 Kuala Lumpur Malaysia
396 Kuantan Malaysia
397 Melaka Malaysia
398 Perai Malaysia
399 Petaling Jaya Malaysia
400 Seremban Malaysia
401 Seri Manjung Malaysia
402 Sungai Petani, Kedah Malaysia
403 Tampin Malaysia
404 Temerloh Malaysia
405 Aguascalientes Mexico
406 Celaya Mexico
407 Chihuahua Mexico
408 Ciudad De Mexico Mexico
409 Ciudad De Mexic Mexico
410 Cuautitlan Izcalli Mexico
411 Culiacan Mexico
412 Culiacán Mexico
413 Durango Mexico
414 El Salto Mexico
415 Guadalajara Mexico
416 Leon Mexico
417 Merida Mexico
418 Mexico City Mexico
419 Mexico Mexico
420 Monterrey Mexico
421 Morelia Mexico
422 Orizaba Mexico
423 Pachuca de Soto Mexico
424 Pachuca Mexico
425 Queretaro Mexico
426 San Luis Potosi Mexico
427 Tlalnepantla de Baz Mexico
428 Veracruz Mexico
429 Zapopan Mexico
430 Auckland New Zealand
431 Christchurch New Zealand
432 Dunedin New Zealand
433 Palmerston North New Zealand
434 Rotorua New Zealand
435 Takapuna Auckland New Zealand
436 Tauranga New Zealand
437 Wellington New Zealand
438 Cagayan De Oro City Philippines
439 Cebuu City Philippines
440 Cebu Philippines
441 Davao City Philippines
442 Iloilo City Philippines
443 Lipa City Philippines
444 Marikina City Philippines
445 Pasay City Philippines
446 Pasig Philippines
447 Quezon City Philippines
448 San Fernando Philippines
449 Tagbilaran City Philippines
450 Taytay Philippines
451 Bydgoszcz Poland
452 Chorzow Poland
453 Katowice Poland
454 Krakow Poland
455 Lodz Poland
456 Lublin Poland
457 Parczew Poland
458 Poznan Poland
459 Radom Poland
460 Rzeszow Poland
461 Torun Poland
462 Warswa Poland
463 Wroclaw Poland
464 Zgierz Poland
465 Znin Poland
466 Caguas Puerto Rico
467 Ponce Puerto Rico
468 San Juan Puerto Rico
469 Brasov Romania
470 Bucuresti Romania
471 Cluj Napoca Romania
472 Deva Romania
473 Iasi Romania
474 Oradea Romania
475 Ploiesti Romania
476 Targu Mures Romania
477 Timisoara Romania
478 Arkhangelsk Russian Federation
479 Barnaul Russian Federation
480 Ivanovo Russian Federation
481 Kemerovo Russian Federation
482 Moscow Russian Federation
483 Novosibirsk Russian Federation
484 Petrozavodsk Russian Federation
485 Rostov-on-Don Russian Federation
486 Ryazan Russian Federation
487 Saint Petersburg Russian Federation
488 Saint-Petersburg Russian Federation
489 Saratov Russian Federation
490 Sestroretsk, Saint-Petersburg Russian Federation
491 St. Petersburg Russian Federation
492 Tomsk Russian Federation
493 Ufa Russian Federation
494 Volgograd Russian Federation
495 Yaroslavl Russian Federation
496 Belgrade Serbia
497 Nis Serbia
498 Zajecar Serbia
499 Bardejov Slovakia
500 Bratislava Slovakia
501 Kosice Slovakia
502 Lubochna Slovakia
503 Nitra Slovakia
504 Prievidza Slovakia
505 Puchov Slovakia
506 Rimavska Sobota Slovakia
507 Sturovo Slovakia
508 Svidnik Slovakia
509 Zilina Slovakia
510 Cape Town South Africa
511 Durban South Africa
512 Isipingo Rail South Africa
513 Johannesburg South Africa
514 Krugersdorp South Africa
515 Port Elizabeth South Africa
516 Pretoria Gauteng South Africa
517 Pretoria South Africa
518 Soweto South Africa
519 A Coruna Spain
520 Almeria Spain
521 Barcelona Spain
522 Burela Spain
523 Ciudad Real Spain
524 Getafe Spain
525 Girona Spain
526 Granada Spain
527 La Roca del Vallès Spain
528 Madrid Spain
529 Majadahonda Spain
530 Málaga Spain
531 Palma de Mallorca Spain
532 Pozuelo de Alarcón Spain
533 Sagunto Spain
534 Santander Spain
535 Sevilla Spain
536 Valencia Spain
537 Vic Spain
538 Viladecans Spain
539 Kaohsiung Taiwan
540 New Taipei City Taiwan
541 Taichung Taiwan
542 Taipei Taiwan
543 Chernivtsi Ukraine
544 Dnipropetrovsk Ukraine
545 Ivano-Frankivsk Ukraine
546 Kharkiv Ukraine
547 Kiev Ukraine
548 Kyiv Ukraine
549 Ternopil Ukraine
550 Vinnitsya Ukraine
551 Vinnytsia Ukraine
552 Zaporizhzhia Ukraine
553 Ajman United Arab Emirates
554 Dubai United Arab Emirates
555 Sharjah United Arab Emirates
556 Aberdeen United Kingdom
557 Antrim United Kingdom
558 Barry United Kingdom
559 Birmingham United Kingdom
560 Blackburn United Kingdom
561 Bolton United Kingdom
562 Bournemouth United Kingdom
563 Bradford United Kingdom
564 Bristol United Kingdom
565 Burbage United Kingdom
566 Cardff United Kingdom
567 Cardiff United Kingdom
568 Carlshalton United Kingdom
569 Carmarthen United Kingdom
570 Chester United Kingdom
571 Darlington United Kingdom
572 Doncaster United Kingdom
573 Durham United Kingdom
574 Ely United Kingdom
575 Hampstead United Kingdom
576 Harlow United Kingdom
577 Huntingdon United Kingdom
578 Leamington Spa United Kingdom
579 Liskeard United Kingdom
580 London United Kingdom
581 Middlesbrough United Kingdom
582 Plymouth United Kingdom
583 Rhyl United Kingdom
584 Rugby United Kingdom
585 Salford United Kingdom
586 Stoke On Trent United Kingdom
587 Swansea United Kingdom
588 Torpoint United Kingdom
589 Watford United Kingdom
590 Welwyn Garden City United Kingdom
591 Westcliff on Sea United Kingdom
592 Wokingham United Kingdom
593 Wolverhampton United Kingdom

Sponsors and Collaborators

  • Janssen Research & Development, LLC
  • The George Institute for Global Health, Australia

Investigators

  • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02065791
Other Study ID Numbers:
  • CR103517
  • 2013-004494-28
  • 28431754DNE3001
First Posted:
Feb 19, 2014
Last Update Posted:
Dec 5, 2019
Last Verified:
Dec 1, 2019
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Janssen Research & Development, LLC
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Canagliflozin
JNJ-28431754
End-Stage Kidney Disease
Chronic Kidney Disease
Macroalbuminuria
Additional relevant MeSH terms:
Kidney Diseases
Diabetic Nephropathies
Diabetes Mellitus
Diabetes Mellitus, Type 2
Canagliflozin

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail A total of 12900 participants were pre-screened, of those, 8932 were screened. A total of 4401 participants were randomized, with 2199 and 2202 participants assigned to placebo and canagliflozin 100 milligrams (mg), respectively.
Arm/Group Title Placebo Canagliflozin 100 mg
Arm/Group Description Participants received matching placebo orally once daily. Participants received canagliflozin 100 milligram (mg) orally once daily.
Period Title: Overall Study
STARTED 2199 2202
Treated 2197 2200
COMPLETED 2174 2187
NOT COMPLETED 25 15

Baseline Characteristics

Arm/Group Title Placebo Canagliflozin 100 mg Total
Arm/Group Description Participants received matching placebo orally once daily. Participants received canagliflozin 100 milligram (mg) orally once daily. Total of all reporting groups
Overall Participants 2199 2202 4401
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
63.2
(9.23)
62.9
(9.17)
63
(9.2)
Sex: Female, Male (Count of Participants)
Female
732
33.3%
762
34.6%
1494
33.9%
Male
1467
66.7%
1440
65.4%
2907
66.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
706
32.1%
717
32.6%
1423
32.3%
Not Hispanic or Latino
1457
66.3%
1436
65.2%
2893
65.7%
Unknown or Not Reported
36
1.6%
49
2.2%
85
1.9%
Race/Ethnicity, Customized (Count of Participants)
Asian
452
20.6%
425
19.3%
877
19.9%
Black or African American
112
5.1%
112
5.1%
224
5.1%
Hispanic or Latino
554
25.2%
567
25.7%
1121
25.5%
Other
199
9%
189
8.6%
388
8.8%
White Non-Hispanic
882
40.1%
909
41.3%
1791
40.7%
Region of Enrollment (Count of Participants)
ARGENTINA
205
9.3%
221
10%
426
9.7%
AUSTRALIA
18
0.8%
20
0.9%
38
0.9%
BRAZIL
162
7.4%
152
6.9%
314
7.1%
BULGARIA
13
0.6%
16
0.7%
29
0.7%
CANADA
93
4.2%
79
3.6%
172
3.9%
CHILE
30
1.4%
22
1%
52
1.2%
CHINA
63
2.9%
66
3%
129
2.9%
COLOMBIA
42
1.9%
52
2.4%
94
2.1%
CZECH REPUBLIC
26
1.2%
31
1.4%
57
1.3%
FRANCE
33
1.5%
28
1.3%
61
1.4%
GERMANY
6
0.3%
5
0.2%
11
0.2%
GUATEMALA
26
1.2%
29
1.3%
55
1.2%
HUNGARY
68
3.1%
67
3%
135
3.1%
INDIA
82
3.7%
62
2.8%
144
3.3%
ITALY
39
1.8%
51
2.3%
90
2%
JAPAN
53
2.4%
57
2.6%
110
2.5%
LITHUANIA
3
0.1%
4
0.2%
7
0.2%
MALAYSIA
72
3.3%
63
2.9%
135
3.1%
MEXICO
152
6.9%
151
6.9%
303
6.9%
NEW ZEALAND
30
1.4%
31
1.4%
61
1.4%
PHILIPPINES
35
1.6%
36
1.6%
71
1.6%
POLAND
27
1.2%
23
1%
50
1.1%
ROMANIA
27
1.2%
32
1.5%
59
1.3%
RUSSIAN FEDERATION
76
3.5%
57
2.6%
133
3%
SERBIA
19
0.9%
21
1%
40
0.9%
SLOVAKIA
32
1.5%
34
1.5%
66
1.5%
SOUTH AFRICA
34
1.5%
28
1.3%
62
1.4%
SOUTH KOREA
58
2.6%
64
2.9%
122
2.8%
SPAIN
58
2.6%
83
3.8%
141
3.2%
TAIWAN
22
1%
15
0.7%
37
0.8%
UKRAINE
173
7.9%
198
9%
371
8.4%
UNITED ARAB EMIRATES
0
0%
1
0%
1
0%
UNITED KINGDOM
59
2.7%
59
2.7%
118
2.7%
UNITED STATES
363
16.5%
344
15.6%
707
16.1%

Outcome Measures

1. Primary Outcome
Title Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (ESKD), and Renal or Cardiovascular (CV) Death
Description Primary composite endpoint is the composite of DoSC, ESKD, and renal or CV death. DoSC: from baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). ESKD: as initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an estimated glomerular filtration rate (eGFR) value of less than (<)15 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who had reached ESKD, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by Endpoint Adjudication Committee (EAC) was performed in blinded fashion. Event rate estimated based on time to first occurrence of primary composite endpoint are presented.
Time Frame Up to 4.6 years

Outcome Measure Data

Analysis Population Description
The Intent-to-treat (ITT) population consisted of all randomized participants.
Arm/Group Title Placebo Canagliflozin 100 mg
Arm/Group Description Participants received matching placebo orally once daily. Participants received canagliflozin 100 milligram (mg) orally once daily.
Measure Participants 2199 2202
Number [Event rate per 1000 participant-years]
61.24
43.21
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value < 0.0001
Comments
Method Cox Proportional Hazard
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.59 to 0.82
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Composite Endpoint of CV Death and Hospitalized Heart Failure (HHF)
Description The composite endpoint included CV death and HHF. CV death included death due to myocardial infarction (MI), stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the composite endpoint of CV death and HHF are presented.
Time Frame Up to 4.6 years

Outcome Measure Data

Analysis Population Description
The ITT population consisted of all randomized participants.
Arm/Group Title Placebo Canagliflozin 100 mg
Arm/Group Description Participants received matching placebo orally once daily. Participants received canagliflozin 100 milligram (mg) orally once daily.
Measure Participants 2199 2202
Number [Event rate per 1000 participant-years]
45.44
31.47
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.0001
Comments
Method Cox proportional hazard
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.57 to 0.83
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Major Adverse Cardiac Event (MACE)
Description The composite endpoint included CV death, non-fatal MI, and non-fatal stroke (that is, 3-point MACE). Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of MACE are presented.
Time Frame Up to 4.6 years

Outcome Measure Data

Analysis Population Description
The ITT population consisted of all randomized participants.
Arm/Group Title Placebo Canagliflozin 100 mg
Arm/Group Description Participants received matching placebo orally once daily. Participants received canagliflozin 100 milligram (mg) orally once daily.
Measure Participants 2199 2202
Number [Event rate per 1000 participant-years]
48.67
38.71
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.0121
Comments
Method Cox proportional hazard
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.67 to 0.95
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Hospitalized Heart Failure (HHF)
Description Adjudication of these events by the Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of hospitalized heart failure are presented.
Time Frame Up to 4.6 years

Outcome Measure Data

Analysis Population Description
The ITT population consisted of all randomized participants.
Arm/Group Title Placebo Canagliflozin 100 mg
Arm/Group Description Participants received matching placebo orally once daily. Participants received canagliflozin 100 milligram (mg) orally once daily.
Measure Participants 2199 2202
Number [Event rate per 1000 participant-years]
25.33
15.65
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.0003
Comments
Method Cox proportional hazards
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.47 to 0.80
Parameter Dispersion Type:
Value:
Estimation Comments
5. Secondary Outcome
Title Renal Composite Endpoint
Description The renal composite endpoint included composite of DoSC, ESKD and Renal death. DoSC: from the baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). ESKD: initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an eGFR value of <15 mL/min/1.73 m^2 (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who have reached ESKD, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the renal composite endpoint are presented.
Time Frame Up to 4.6 years

Outcome Measure Data

Analysis Population Description
The ITT population consisted of all randomized participant.
Arm/Group Title Placebo Canagliflozin 100 mg
Arm/Group Description Participants received matching placebo orally once daily. Participants received canagliflozin 100 milligram (mg) orally once daily.
Measure Participants 2199 2202
Number [Event rate per 1000 participant-years]
40.36
26.99
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Cox proportional hazards
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.53 to 0.81
Parameter Dispersion Type:
Value:
Estimation Comments
6. Secondary Outcome
Title Cardiovascular (CV) Death
Description CV death included death due to MI, stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was a CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of CV death are presented.
Time Frame Up to 4.6 years

Outcome Measure Data

Analysis Population Description
The ITT population consisted of all randomized participants.
Arm/Group Title Placebo Canagliflozin 100 mg
Arm/Group Description Participants received matching placebo orally once daily. Participants received canagliflozin 100 milligram (mg) orally once daily.
Measure Participants 2199 2202
Number [Event rate per 1000 participant-years]
24.38
19.01
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.0502
Comments
Method Cox proportional hazards
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.61 to 1.00
Parameter Dispersion Type:
Value:
Estimation Comments
7. Secondary Outcome
Title All-cause Mortality
Description Adjudication of these events by Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on time to first occurrence of all-cause mortality are presented.
Time Frame Up to 4.6 years

Outcome Measure Data

Analysis Population Description
The ITT population consisted of all randomized participants.
Arm/Group Title Placebo Canagliflozin 100 mg
Arm/Group Description Participants received matching placebo orally once daily. Participants received canagliflozin 100 milligram (mg) orally once daily.
Measure Participants 2199 2202
Number [Event rate per 1000 participant-years]
35.00
29.04
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value = 0.0727
Comments
Method Cox proportional hazard
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.68 to 1.02
Parameter Dispersion Type:
Value:
Estimation Comments
8. Secondary Outcome
Title CV Composite Endpoint
Description The CV composite endpoint included the CV death, non-fatal MI, non-fatal stroke, hospitalized heart failure, and hospitalized unstable angina. CV death included death due to MI, stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was a CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the CV composite endpoint are presented.
Time Frame Up to 4.6 years

Outcome Measure Data

Analysis Population Description
The ITT population consisted of all randomized participant.
Arm/Group Title Placebo Canagliflozin 100 mg
Arm/Group Description Participants received matching placebo orally once daily. Participants received canagliflozin 100 milligram (mg) orally once daily.
Measure Participants 2199 2202
Number [Event rate per 1000 participant-years]
66.95
49.35
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0001
Comments
Method Cox proportional hazards
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.63 to 0.86
Parameter Dispersion Type:
Value:
Estimation Comments

Adverse Events

Time Frame Up to 4.6 years
Adverse Event Reporting Description Safety population included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Placebo Canagliflozin 100 mg
Arm/Group Description Participants received matching placebo orally once daily. Participants received canagliflozin 100 milligram (mg) orally once daily.
All Cause Mortality
Placebo Canagliflozin 100 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 193/2197 (8.8%) 164/2200 (7.5%)
Serious Adverse Events
Placebo Canagliflozin 100 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 806/2197 (36.7%) 737/2200 (33.5%)
Blood and lymphatic system disorders
Anaemia 10/2197 (0.5%) 7/2200 (0.3%)
Anaemia Vitamin B12 Deficiency 0/2197 (0%) 1/2200 (0%)
Bicytopenia 1/2197 (0%) 0/2200 (0%)
Disseminated Intravascular Coagulation 0/2197 (0%) 1/2200 (0%)
Haemorrhagic Anaemia 2/2197 (0.1%) 2/2200 (0.1%)
Hypochromic Anaemia 0/2197 (0%) 1/2200 (0%)
Iron Deficiency Anaemia 0/2197 (0%) 2/2200 (0.1%)
Lymphadenopathy 0/2197 (0%) 1/2200 (0%)
Nephrogenic Anaemia 2/2197 (0.1%) 1/2200 (0%)
Normochromic Normocytic Anaemia 1/2197 (0%) 0/2200 (0%)
Normocytic Anaemia 1/2197 (0%) 0/2200 (0%)
Pancytopenia 0/2197 (0%) 1/2200 (0%)
Thrombocytopenia 1/2197 (0%) 0/2200 (0%)
Cardiac disorders
Acute Coronary Syndrome 8/2197 (0.4%) 12/2200 (0.5%)
Acute Left Ventricular Failure 4/2197 (0.2%) 0/2200 (0%)
Acute Myocardial Infarction 38/2197 (1.7%) 38/2200 (1.7%)
Angina Pectoris 14/2197 (0.6%) 21/2200 (1%)
Angina Unstable 29/2197 (1.3%) 17/2200 (0.8%)
Arrhythmia 1/2197 (0%) 2/2200 (0.1%)
Arteriosclerosis Coronary Artery 3/2197 (0.1%) 4/2200 (0.2%)
Atrial Fibrillation 19/2197 (0.9%) 16/2200 (0.7%)
Atrial Flutter 2/2197 (0.1%) 2/2200 (0.1%)
Atrioventricular Block 2/2197 (0.1%) 2/2200 (0.1%)
Atrioventricular Block Complete 2/2197 (0.1%) 1/2200 (0%)
Atrioventricular Block First Degree 0/2197 (0%) 1/2200 (0%)
Bradycardia 3/2197 (0.1%) 2/2200 (0.1%)
Brugada Syndrome 1/2197 (0%) 0/2200 (0%)
Cardiac Arrest 7/2197 (0.3%) 5/2200 (0.2%)
Cardiac Asthma 1/2197 (0%) 0/2200 (0%)
Cardiac Disorder 1/2197 (0%) 0/2200 (0%)
Cardiac Failure 50/2197 (2.3%) 34/2200 (1.5%)
Cardiac Failure Acute 6/2197 (0.3%) 6/2200 (0.3%)
Cardiac Failure Chronic 4/2197 (0.2%) 2/2200 (0.1%)
Cardiac Failure Congestive 48/2197 (2.2%) 24/2200 (1.1%)
Cardiac Fibrillation 1/2197 (0%) 0/2200 (0%)
Cardiac Tamponade 0/2197 (0%) 1/2200 (0%)
Cardio-Respiratory Arrest 3/2197 (0.1%) 4/2200 (0.2%)
Cardiogenic Shock 8/2197 (0.4%) 2/2200 (0.1%)
Cardiomyopathy 2/2197 (0.1%) 0/2200 (0%)
Cardiorenal Syndrome 1/2197 (0%) 1/2200 (0%)
Chronic Left Ventricular Failure 1/2197 (0%) 0/2200 (0%)
Chronic Right Ventricular Failure 1/2197 (0%) 0/2200 (0%)
Cor Pulmonale 0/2197 (0%) 1/2200 (0%)
Coronary Artery Disease 23/2197 (1%) 9/2200 (0.4%)
Coronary Artery Insufficiency 2/2197 (0.1%) 1/2200 (0%)
Coronary Artery Occlusion 0/2197 (0%) 3/2200 (0.1%)
Coronary Artery Stenosis 5/2197 (0.2%) 3/2200 (0.1%)
Hypertensive Heart Disease 0/2197 (0%) 2/2200 (0.1%)
Ischaemic Cardiomyopathy 6/2197 (0.3%) 4/2200 (0.2%)
Left Ventricular Failure 5/2197 (0.2%) 3/2200 (0.1%)
Mitral Valve Incompetence 3/2197 (0.1%) 1/2200 (0%)
Myocardial Infarction 27/2197 (1.2%) 22/2200 (1%)
Myocardial Ischaemia 8/2197 (0.4%) 8/2200 (0.4%)
Myocarditis 0/2197 (0%) 1/2200 (0%)
Pericardial Effusion 2/2197 (0.1%) 2/2200 (0.1%)
Pericardial Haemorrhage 1/2197 (0%) 0/2200 (0%)
Pericarditis 1/2197 (0%) 1/2200 (0%)
Pulseless Electrical Activity 1/2197 (0%) 1/2200 (0%)
Right Ventricular Failure 0/2197 (0%) 1/2200 (0%)
Sinus Node Dysfunction 1/2197 (0%) 0/2200 (0%)
Supraventricular Tachycardia 1/2197 (0%) 0/2200 (0%)
Tricuspid Valve Incompetence 2/2197 (0.1%) 0/2200 (0%)
Ventricular Arrhythmia 1/2197 (0%) 0/2200 (0%)
Ventricular Extrasystoles 1/2197 (0%) 2/2200 (0.1%)
Ventricular Fibrillation 2/2197 (0.1%) 1/2200 (0%)
Ventricular Tachycardia 2/2197 (0.1%) 1/2200 (0%)
Ear and labyrinth disorders
Vertigo 3/2197 (0.1%) 2/2200 (0.1%)
Vertigo Positional 0/2197 (0%) 1/2200 (0%)
Endocrine disorders
Goitre 0/2197 (0%) 2/2200 (0.1%)
Hyperparathyroidism 1/2197 (0%) 0/2200 (0%)
Hyperthyroidism 1/2197 (0%) 0/2200 (0%)
Hypothyroidism 0/2197 (0%) 1/2200 (0%)
Inappropriate Antidiuretic Hormone Secretion 0/2197 (0%) 1/2200 (0%)
Thyroid Mass 0/2197 (0%) 2/2200 (0.1%)
Eye disorders
Amaurosis 1/2197 (0%) 0/2200 (0%)
Angle Closure Glaucoma 1/2197 (0%) 0/2200 (0%)
Cataract 9/2197 (0.4%) 8/2200 (0.4%)
Cataract Subcapsular 1/2197 (0%) 0/2200 (0%)
Diabetic Retinopathy 4/2197 (0.2%) 7/2200 (0.3%)
Eye Haemorrhage 3/2197 (0.1%) 1/2200 (0%)
Eyelid Ptosis 1/2197 (0%) 0/2200 (0%)
Glaucoma 2/2197 (0.1%) 1/2200 (0%)
Keratitis 1/2197 (0%) 0/2200 (0%)
Maculopathy 0/2197 (0%) 2/2200 (0.1%)
Neovascular Age-Related Macular Degeneration 1/2197 (0%) 0/2200 (0%)
Optic Ischaemic Neuropathy 0/2197 (0%) 1/2200 (0%)
Retinal Detachment 2/2197 (0.1%) 3/2200 (0.1%)
Rhegmatogenous Retinal Detachment 1/2197 (0%) 0/2200 (0%)
Tractional Retinal Detachment 1/2197 (0%) 0/2200 (0%)
Uveitis 0/2197 (0%) 1/2200 (0%)
Vision Blurred 1/2197 (0%) 0/2200 (0%)
Visual Impairment 2/2197 (0.1%) 1/2200 (0%)
Vitreous Adhesions 0/2197 (0%) 1/2200 (0%)
Vitreous Haemorrhage 1/2197 (0%) 4/2200 (0.2%)
Gastrointestinal disorders
Abdominal Fat Apron 0/2197 (0%) 1/2200 (0%)
Abdominal Incarcerated Hernia 0/2197 (0%) 1/2200 (0%)
Abdominal Pain 2/2197 (0.1%) 0/2200 (0%)
Abdominal Pain Lower 0/2197 (0%) 1/2200 (0%)
Abdominal Pain Upper 1/2197 (0%) 0/2200 (0%)
Anal Fistula 1/2197 (0%) 0/2200 (0%)
Anal Haemorrhage 0/2197 (0%) 1/2200 (0%)
Chronic Gastritis 1/2197 (0%) 0/2200 (0%)
Colitis 0/2197 (0%) 1/2200 (0%)
Colitis Ischaemic 2/2197 (0.1%) 0/2200 (0%)
Constipation 2/2197 (0.1%) 0/2200 (0%)
Diabetic Gastroparesis 1/2197 (0%) 0/2200 (0%)
Diarrhoea 2/2197 (0.1%) 3/2200 (0.1%)
Diverticulum 0/2197 (0%) 1/2200 (0%)
Diverticulum Intestinal 1/2197 (0%) 0/2200 (0%)
Diverticulum Intestinal Haemorrhagic 0/2197 (0%) 1/2200 (0%)
Duodenal Ulcer 1/2197 (0%) 2/2200 (0.1%)
Duodenal Ulcer Haemorrhage 1/2197 (0%) 0/2200 (0%)
Duodenitis 0/2197 (0%) 2/2200 (0.1%)
Enteritis 3/2197 (0.1%) 0/2200 (0%)
Enterocolitis 1/2197 (0%) 0/2200 (0%)
Enterovesical Fistula 1/2197 (0%) 0/2200 (0%)
Epulis 1/2197 (0%) 0/2200 (0%)
Faeces Discoloured 0/2197 (0%) 1/2200 (0%)
Food Poisoning 0/2197 (0%) 1/2200 (0%)
Gastric Ulcer 0/2197 (0%) 2/2200 (0.1%)
Gastritis 1/2197 (0%) 3/2200 (0.1%)
Gastrointestinal Haemorrhage 6/2197 (0.3%) 4/2200 (0.2%)
Gastrooesophageal Reflux Disease 2/2197 (0.1%) 0/2200 (0%)
Haematemesis 1/2197 (0%) 0/2200 (0%)
Haemorrhoidal Haemorrhage 1/2197 (0%) 0/2200 (0%)
Ileus 1/2197 (0%) 0/2200 (0%)
Incarcerated Inguinal Hernia 1/2197 (0%) 0/2200 (0%)
Inguinal Hernia 1/2197 (0%) 4/2200 (0.2%)
Intestinal Obstruction 1/2197 (0%) 7/2200 (0.3%)
Intestinal Perforation 0/2197 (0%) 1/2200 (0%)
Large Intestine Polyp 2/2197 (0.1%) 1/2200 (0%)
Leukoplakia Oral 0/2197 (0%) 1/2200 (0%)
Lower Gastrointestinal Haemorrhage 0/2197 (0%) 1/2200 (0%)
Melaena 0/2197 (0%) 1/2200 (0%)
Obstructive Pancreatitis 0/2197 (0%) 1/2200 (0%)
Pancreatitis 0/2197 (0%) 4/2200 (0.2%)
Pancreatitis Acute 3/2197 (0.1%) 3/2200 (0.1%)
Peptic Ulcer 1/2197 (0%) 0/2200 (0%)
Peptic Ulcer Haemorrhage 1/2197 (0%) 0/2200 (0%)
Rectal Haemorrhage 1/2197 (0%) 1/2200 (0%)
Rectal Polyp 0/2197 (0%) 1/2200 (0%)
Small Intestinal Haemorrhage 0/2197 (0%) 1/2200 (0%)
Small Intestinal Obstruction 2/2197 (0.1%) 1/2200 (0%)
Subileus 1/2197 (0%) 0/2200 (0%)
Swollen Tongue 1/2197 (0%) 0/2200 (0%)
Umbilical Hernia 0/2197 (0%) 1/2200 (0%)
Upper Gastrointestinal Haemorrhage 1/2197 (0%) 4/2200 (0.2%)
Vomiting 4/2197 (0.2%) 1/2200 (0%)
General disorders
Asthenia 2/2197 (0.1%) 0/2200 (0%)
Atrophy 1/2197 (0%) 0/2200 (0%)
Cardiac Death 1/2197 (0%) 3/2200 (0.1%)
Chest Discomfort 1/2197 (0%) 1/2200 (0%)
Chest Pain 3/2197 (0.1%) 1/2200 (0%)
Complication Associated with Device 0/2197 (0%) 1/2200 (0%)
Critical Illness 0/2197 (0%) 1/2200 (0%)
Cyst 1/2197 (0%) 0/2200 (0%)
Death 6/2197 (0.3%) 7/2200 (0.3%)
Drowning 1/2197 (0%) 0/2200 (0%)
Gait Disturbance 0/2197 (0%) 1/2200 (0%)
General Physical Health Deterioration 0/2197 (0%) 1/2200 (0%)
Generalised Oedema 2/2197 (0.1%) 2/2200 (0.1%)
Incarcerated Hernia 0/2197 (0%) 1/2200 (0%)
Influenza Like Illness 1/2197 (0%) 0/2200 (0%)
Localised Oedema 1/2197 (0%) 0/2200 (0%)
Multiple Organ Dysfunction Syndrome 2/2197 (0.1%) 1/2200 (0%)
Necrobiosis 1/2197 (0%) 0/2200 (0%)
Non-Cardiac Chest Pain 2/2197 (0.1%) 8/2200 (0.4%)
Oedema Peripheral 4/2197 (0.2%) 3/2200 (0.1%)
Peripheral Swelling 3/2197 (0.1%) 1/2200 (0%)
Pyrexia 1/2197 (0%) 2/2200 (0.1%)
Sudden Cardiac Death 2/2197 (0.1%) 2/2200 (0.1%)
Sudden Death 8/2197 (0.4%) 3/2200 (0.1%)
Systemic Inflammatory Response Syndrome 0/2197 (0%) 1/2200 (0%)
Hepatobiliary disorders
Bile Duct Obstruction 1/2197 (0%) 0/2200 (0%)
Bile Duct Stone 1/2197 (0%) 0/2200 (0%)
Cholangitis 1/2197 (0%) 0/2200 (0%)
Cholangitis Acute 0/2197 (0%) 1/2200 (0%)
Cholangitis Sclerosing 0/2197 (0%) 1/2200 (0%)
Cholecystitis 5/2197 (0.2%) 2/2200 (0.1%)
Cholecystitis Acute 4/2197 (0.2%) 5/2200 (0.2%)
Cholecystitis Chronic 1/2197 (0%) 3/2200 (0.1%)
Cholelithiasis 2/2197 (0.1%) 5/2200 (0.2%)
Hepatic Cirrhosis 2/2197 (0.1%) 1/2200 (0%)
Hepatic Function Abnormal 0/2197 (0%) 1/2200 (0%)
Ischaemic Hepatitis 1/2197 (0%) 0/2200 (0%)
Immune system disorders
Anaphylactic Reaction 1/2197 (0%) 1/2200 (0%)
Drug Hypersensitivity 2/2197 (0.1%) 0/2200 (0%)
Infections and infestations
Abdominal Abscess 1/2197 (0%) 1/2200 (0%)
Abdominal Sepsis 0/2197 (0%) 1/2200 (0%)
Abdominal Wall Abscess 1/2197 (0%) 0/2200 (0%)
Abscess Limb 0/2197 (0%) 3/2200 (0.1%)
Acute Hepatitis B 0/2197 (0%) 1/2200 (0%)
Appendicitis 3/2197 (0.1%) 2/2200 (0.1%)
Appendicitis Perforated 3/2197 (0.1%) 0/2200 (0%)
Arteriovenous Fistula Site Infection 2/2197 (0.1%) 0/2200 (0%)
Arthritis Bacterial 1/2197 (0%) 2/2200 (0.1%)
Atypical Pneumonia 0/2197 (0%) 1/2200 (0%)
Bacteraemia 1/2197 (0%) 1/2200 (0%)
Bacterial Pyelonephritis 1/2197 (0%) 0/2200 (0%)
Bacterial Sepsis 1/2197 (0%) 0/2200 (0%)
Bronchiolitis 1/2197 (0%) 0/2200 (0%)
Bronchitis 7/2197 (0.3%) 5/2200 (0.2%)
Bronchitis Viral 1/2197 (0%) 0/2200 (0%)
Campylobacter Colitis 0/2197 (0%) 1/2200 (0%)
Cellulitis 26/2197 (1.2%) 18/2200 (0.8%)
Cellulitis Staphylococcal 1/2197 (0%) 0/2200 (0%)
Chronic Sinusitis 2/2197 (0.1%) 0/2200 (0%)
Clostridium Difficile Colitis 1/2197 (0%) 2/2200 (0.1%)
Clostridium Difficile Infection 0/2197 (0%) 1/2200 (0%)
Cystitis 0/2197 (0%) 2/2200 (0.1%)
Dengue Fever 1/2197 (0%) 0/2200 (0%)
Device Related Infection 0/2197 (0%) 1/2200 (0%)
Diabetic Foot Infection 4/2197 (0.2%) 3/2200 (0.1%)
Diabetic Gangrene 2/2197 (0.1%) 5/2200 (0.2%)
Diverticulitis 2/2197 (0.1%) 4/2200 (0.2%)
Dysentery 1/2197 (0%) 0/2200 (0%)
Ear Infection 0/2197 (0%) 1/2200 (0%)
Empyema 0/2197 (0%) 1/2200 (0%)
Endocarditis 1/2197 (0%) 0/2200 (0%)
Endophthalmitis 1/2197 (0%) 0/2200 (0%)
Enteritis Infectious 1/2197 (0%) 0/2200 (0%)
Enterobacter Infection 0/2197 (0%) 1/2200 (0%)
Enterocolitis Bacterial 1/2197 (0%) 0/2200 (0%)
Epididymitis 1/2197 (0%) 0/2200 (0%)
Erysipelas 5/2197 (0.2%) 2/2200 (0.1%)
Escherichia Sepsis 1/2197 (0%) 0/2200 (0%)
Furuncle 1/2197 (0%) 0/2200 (0%)
Gangrene 15/2197 (0.7%) 10/2200 (0.5%)
Gas Gangrene 0/2197 (0%) 1/2200 (0%)
Gastroenteritis 19/2197 (0.9%) 6/2200 (0.3%)
Gastroenteritis Bacterial 0/2197 (0%) 1/2200 (0%)
Gastroenteritis Viral 1/2197 (0%) 0/2200 (0%)
Gastrointestinal Bacterial Infection 1/2197 (0%) 0/2200 (0%)
Giardiasis 1/2197 (0%) 0/2200 (0%)
Graft Infection 0/2197 (0%) 1/2200 (0%)
Groin Abscess 1/2197 (0%) 0/2200 (0%)
Haemophilus Infection 0/2197 (0%) 1/2200 (0%)
Hepatic Echinococciasis 1/2197 (0%) 0/2200 (0%)
Herpes Zoster 1/2197 (0%) 0/2200 (0%)
Infected Skin Ulcer 6/2197 (0.3%) 5/2200 (0.2%)
Infection in An Immunocompromised Host 1/2197 (0%) 0/2200 (0%)
Infective Exacerbation of Chronic Obstructive Airways Disease 1/2197 (0%) 0/2200 (0%)
Influenza 1/2197 (0%) 3/2200 (0.1%)
Intervertebral Discitis 1/2197 (0%) 0/2200 (0%)
Keratitis Fungal 2/2197 (0.1%) 0/2200 (0%)
Laryngitis 0/2197 (0%) 1/2200 (0%)
Liver Abscess 1/2197 (0%) 0/2200 (0%)
Localised Infection 6/2197 (0.3%) 6/2200 (0.3%)
Lower Respiratory Tract Infection 3/2197 (0.1%) 2/2200 (0.1%)
Lung Infection 3/2197 (0.1%) 2/2200 (0.1%)
Mediastinitis 2/2197 (0.1%) 0/2200 (0%)
Meningitis 1/2197 (0%) 0/2200 (0%)
Meningitis Bacterial 1/2197 (0%) 0/2200 (0%)
Necrotising Fasciitis 0/2197 (0%) 2/2200 (0.1%)
Onychomycosis 0/2197 (0%) 1/2200 (0%)
Opisthorchiasis 1/2197 (0%) 0/2200 (0%)
Orchitis 1/2197 (0%) 1/2200 (0%)
Osteomyelitis 11/2197 (0.5%) 11/2200 (0.5%)
Osteomyelitis Acute 0/2197 (0%) 2/2200 (0.1%)
Osteomyelitis Chronic 0/2197 (0%) 1/2200 (0%)
Perineal Abscess 0/2197 (0%) 1/2200 (0%)
Periodontitis 1/2197 (0%) 0/2200 (0%)
Pharyngeal Abscess 0/2197 (0%) 1/2200 (0%)
Pneumonia 86/2197 (3.9%) 63/2200 (2.9%)
Pneumonia Bacterial 2/2197 (0.1%) 0/2200 (0%)
Pneumonia Influenzal 1/2197 (0%) 0/2200 (0%)
Pneumonia Pneumococcal 0/2197 (0%) 1/2200 (0%)
Pneumonia Staphylococcal 1/2197 (0%) 0/2200 (0%)
Pneumonia Streptococcal 0/2197 (0%) 1/2200 (0%)
Pneumonia Viral 1/2197 (0%) 0/2200 (0%)
Postoperative Wound Infection 3/2197 (0.1%) 2/2200 (0.1%)
Pseudomonas Bronchitis 1/2197 (0%) 0/2200 (0%)
Pulmonary Sepsis 0/2197 (0%) 1/2200 (0%)
Pyelonephritis 5/2197 (0.2%) 3/2200 (0.1%)
Pyelonephritis Acute 2/2197 (0.1%) 4/2200 (0.2%)
Pyelonephritis Chronic 2/2197 (0.1%) 0/2200 (0%)
Rectal Abscess 0/2197 (0%) 1/2200 (0%)
Respiratory Syncytial Virus Bronchiolitis 1/2197 (0%) 0/2200 (0%)
Respiratory Tract Infection 2/2197 (0.1%) 2/2200 (0.1%)
Respiratory Tract Infection Viral 0/2197 (0%) 1/2200 (0%)
Rhinitis 1/2197 (0%) 0/2200 (0%)
Scrotal Abscess 1/2197 (0%) 1/2200 (0%)
Scrub Typhus 0/2197 (0%) 1/2200 (0%)
Sepsis 12/2197 (0.5%) 11/2200 (0.5%)
Septic Shock 12/2197 (0.5%) 5/2200 (0.2%)
Soft Tissue Infection 0/2197 (0%) 1/2200 (0%)
Staphylococcal Bacteraemia 1/2197 (0%) 0/2200 (0%)
Staphylococcal Infection 0/2197 (0%) 1/2200 (0%)
Staphylococcal Sepsis 2/2197 (0.1%) 2/2200 (0.1%)
Streptococcal Infection 1/2197 (0%) 0/2200 (0%)
Subcutaneous Abscess 0/2197 (0%) 1/2200 (0%)
Tonsillitis 0/2197 (0%) 1/2200 (0%)
Tooth Abscess 1/2197 (0%) 0/2200 (0%)
Tracheobronchitis 1/2197 (0%) 0/2200 (0%)
Upper Respiratory Tract Infection 3/2197 (0.1%) 3/2200 (0.1%)
Urinary Tract Infection 21/2197 (1%) 25/2200 (1.1%)
Urinary Tract Infection Fungal 0/2197 (0%) 1/2200 (0%)
Urosepsis 3/2197 (0.1%) 3/2200 (0.1%)
Viral Infection 1/2197 (0%) 1/2200 (0%)
Viral Upper Respiratory Tract Infection 1/2197 (0%) 0/2200 (0%)
Wound Infection 1/2197 (0%) 6/2200 (0.3%)
Injury, poisoning and procedural complications
Anaesthetic Complication 1/2197 (0%) 0/2200 (0%)
Ankle Fracture 3/2197 (0.1%) 0/2200 (0%)
Cervical Vertebral Fracture 1/2197 (0%) 0/2200 (0%)
Chest Injury 1/2197 (0%) 0/2200 (0%)
Clavicle Fracture 1/2197 (0%) 0/2200 (0%)
Concussion 0/2197 (0%) 1/2200 (0%)
Contusion 1/2197 (0%) 0/2200 (0%)
Coronary Artery Reocclusion 1/2197 (0%) 0/2200 (0%)
Coronary Vascular Graft Occlusion 1/2197 (0%) 0/2200 (0%)
Craniocerebral Injury 1/2197 (0%) 1/2200 (0%)
Expired Product Administered 1/2197 (0%) 0/2200 (0%)
Facial Bones Fracture 0/2197 (0%) 1/2200 (0%)
Fall 3/2197 (0.1%) 1/2200 (0%)
Femoral Neck Fracture 2/2197 (0.1%) 4/2200 (0.2%)
Femur Fracture 1/2197 (0%) 5/2200 (0.2%)
Fibula Fracture 0/2197 (0%) 2/2200 (0.1%)
Foot Fracture 0/2197 (0%) 1/2200 (0%)
Foreign Body in Eye 1/2197 (0%) 0/2200 (0%)
Fracture Displacement 0/2197 (0%) 1/2200 (0%)
Head Injury 1/2197 (0%) 1/2200 (0%)
Hip Fracture 5/2197 (0.2%) 3/2200 (0.1%)
Humerus Fracture 2/2197 (0.1%) 4/2200 (0.2%)
Joint Dislocation 0/2197 (0%) 1/2200 (0%)
Joint Injury 1/2197 (0%) 0/2200 (0%)
Ligament Rupture 0/2197 (0%) 1/2200 (0%)
Ligament Sprain 1/2197 (0%) 0/2200 (0%)
Limb Injury 0/2197 (0%) 1/2200 (0%)
Meniscus Injury 0/2197 (0%) 1/2200 (0%)
Muscle Injury 1/2197 (0%) 0/2200 (0%)
Muscle Strain 0/2197 (0%) 1/2200 (0%)
Overdose 1/2197 (0%) 0/2200 (0%)
Patella Fracture 1/2197 (0%) 0/2200 (0%)
Post Procedural Complication 1/2197 (0%) 0/2200 (0%)
Post Procedural Haematoma 1/2197 (0%) 1/2200 (0%)
Post Procedural Haemorrhage 0/2197 (0%) 1/2200 (0%)
Postoperative Thrombosis 0/2197 (0%) 1/2200 (0%)
Postoperative Wound Complication 0/2197 (0%) 1/2200 (0%)
Procedural Intestinal Perforation 1/2197 (0%) 0/2200 (0%)
Procedural Pain 1/2197 (0%) 1/2200 (0%)
Pubis Fracture 0/2197 (0%) 2/2200 (0.1%)
Radius Fracture 1/2197 (0%) 0/2200 (0%)
Rib Fracture 2/2197 (0.1%) 1/2200 (0%)
Road Traffic Accident 0/2197 (0%) 1/2200 (0%)
Soft Tissue Injury 0/2197 (0%) 1/2200 (0%)
Spinal Compression Fracture 1/2197 (0%) 1/2200 (0%)
Spinal Fracture 1/2197 (0%) 0/2200 (0%)
Sternal Fracture 0/2197 (0%) 1/2200 (0%)
Stress Fracture 0/2197 (0%) 1/2200 (0%)
Subarachnoid Haemorrhage 1/2197 (0%) 1/2200 (0%)
Subdural Haematoma 3/2197 (0.1%) 3/2200 (0.1%)
Subdural Haemorrhage 0/2197 (0%) 1/2200 (0%)
Thermal Burn 1/2197 (0%) 2/2200 (0.1%)
Thoracic Vertebral Fracture 0/2197 (0%) 1/2200 (0%)
Tibia Fracture 0/2197 (0%) 2/2200 (0.1%)
Traumatic Intracranial Haemorrhage 1/2197 (0%) 0/2200 (0%)
Ulna Fracture 0/2197 (0%) 2/2200 (0.1%)
Vascular Graft Occlusion 0/2197 (0%) 2/2200 (0.1%)
Wound 5/2197 (0.2%) 0/2200 (0%)
Wound Dehiscence 1/2197 (0%) 1/2200 (0%)
Wound Haemorrhage 1/2197 (0%) 0/2200 (0%)
Wrist Fracture 1/2197 (0%) 0/2200 (0%)
Investigations
Aspiration Bronchial 0/2197 (0%) 1/2200 (0%)
Biopsy Kidney 0/2197 (0%) 1/2200 (0%)
Blood Creatine Phosphokinase Increased 0/2197 (0%) 2/2200 (0.1%)
Blood Creatinine Increased 20/2197 (0.9%) 7/2200 (0.3%)
Blood Glucose Increased 2/2197 (0.1%) 1/2200 (0%)
Blood Osmolarity Decreased 1/2197 (0%) 0/2200 (0%)
Blood Urea Increased 0/2197 (0%) 1/2200 (0%)
Ejection Fraction Decreased 1/2197 (0%) 0/2200 (0%)
Glomerular Filtration Rate Decreased 1/2197 (0%) 5/2200 (0.2%)
Haemoglobin Decreased 1/2197 (0%) 0/2200 (0%)
International Normalised Ratio Increased 1/2197 (0%) 0/2200 (0%)
Troponin Increased 1/2197 (0%) 0/2200 (0%)
Weight Decreased 1/2197 (0%) 0/2200 (0%)
Metabolism and nutrition disorders
Cachexia 0/2197 (0%) 1/2200 (0%)
Dehydration 8/2197 (0.4%) 4/2200 (0.2%)
Diabetes Mellitus 10/2197 (0.5%) 5/2200 (0.2%)
Diabetes Mellitus Inadequate Control 12/2197 (0.5%) 7/2200 (0.3%)
Diabetic Ketoacidosis 2/2197 (0.1%) 9/2200 (0.4%)
Diabetic Ketosis 1/2197 (0%) 0/2200 (0%)
Diabetic Metabolic Decompensation 3/2197 (0.1%) 1/2200 (0%)
Electrolyte Imbalance 1/2197 (0%) 0/2200 (0%)
Fluid Overload 4/2197 (0.2%) 3/2200 (0.1%)
Fluid Retention 0/2197 (0%) 1/2200 (0%)
Hypercalcaemia 1/2197 (0%) 1/2200 (0%)
Hyperglycaemia 11/2197 (0.5%) 1/2200 (0%)
Hyperglycaemic Hyperosmolar Nonketotic Syndrome 2/2197 (0.1%) 1/2200 (0%)
Hyperkalaemia 10/2197 (0.5%) 10/2200 (0.5%)
Hyperlipidaemia 1/2197 (0%) 0/2200 (0%)
Hypoglycaemia 11/2197 (0.5%) 17/2200 (0.8%)
Hypokalaemia 3/2197 (0.1%) 0/2200 (0%)
Hyponatraemia 4/2197 (0.2%) 3/2200 (0.1%)
Hypophagia 0/2197 (0%) 1/2200 (0%)
Hypoproteinaemia 1/2197 (0%) 0/2200 (0%)
Ketoacidosis 1/2197 (0%) 0/2200 (0%)
Lactic Acidosis 0/2197 (0%) 1/2200 (0%)
Metabolic Acidosis 6/2197 (0.3%) 2/2200 (0.1%)
Metabolic Disorder 1/2197 (0%) 0/2200 (0%)
Obesity 1/2197 (0%) 2/2200 (0.1%)
Type 2 Diabetes Mellitus 2/2197 (0.1%) 1/2200 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia 2/2197 (0.1%) 1/2200 (0%)
Back Pain 1/2197 (0%) 2/2200 (0.1%)
Cervical Spinal Stenosis 0/2197 (0%) 1/2200 (0%)
Chest Wall Haematoma 1/2197 (0%) 0/2200 (0%)
Gouty Arthritis 2/2197 (0.1%) 0/2200 (0%)
Haemarthrosis 0/2197 (0%) 1/2200 (0%)
Intervertebral Disc Degeneration 0/2197 (0%) 1/2200 (0%)
Intervertebral Disc Displacement 1/2197 (0%) 0/2200 (0%)
Intervertebral Disc Protrusion 5/2197 (0.2%) 2/2200 (0.1%)
Lumbar Spinal Stenosis 5/2197 (0.2%) 1/2200 (0%)
Muscular Weakness 1/2197 (0%) 2/2200 (0.1%)
Musculoskeletal Chest Pain 1/2197 (0%) 2/2200 (0.1%)
Musculoskeletal Pain 1/2197 (0%) 0/2200 (0%)
Neuropathic Arthropathy 3/2197 (0.1%) 0/2200 (0%)
Osteitis 0/2197 (0%) 1/2200 (0%)
Osteitis Deformans 1/2197 (0%) 0/2200 (0%)
Osteoarthritis 11/2197 (0.5%) 10/2200 (0.5%)
Osteochondrosis 0/2197 (0%) 1/2200 (0%)
Pain in Extremity 2/2197 (0.1%) 2/2200 (0.1%)
Periarthritis 2/2197 (0.1%) 2/2200 (0.1%)
Rotator Cuff Syndrome 1/2197 (0%) 1/2200 (0%)
Spinal Column Stenosis 0/2197 (0%) 1/2200 (0%)
Spinal Disorder 1/2197 (0%) 0/2200 (0%)
Spinal Osteoarthritis 0/2197 (0%) 4/2200 (0.2%)
Spondylolisthesis 1/2197 (0%) 0/2200 (0%)
Symphysiolysis 0/2197 (0%) 1/2200 (0%)
Systemic Lupus Erythematosus 1/2197 (0%) 0/2200 (0%)
Trigger Finger 2/2197 (0.1%) 0/2200 (0%)
Vertebral Foraminal Stenosis 1/2197 (0%) 1/2200 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute Leukaemia 0/2197 (0%) 1/2200 (0%)
Adenocarcinoma Gastric 1/2197 (0%) 0/2200 (0%)
Adenocarcinoma of Colon 1/2197 (0%) 2/2200 (0.1%)
B-Cell Lymphoma 0/2197 (0%) 1/2200 (0%)
Basal Cell Carcinoma 0/2197 (0%) 2/2200 (0.1%)
Benign Neoplasm of Bladder 1/2197 (0%) 0/2200 (0%)
Bladder Cancer 4/2197 (0.2%) 5/2200 (0.2%)
Bladder Neoplasm 1/2197 (0%) 0/2200 (0%)
Bladder Transitional Cell Carcinoma 2/2197 (0.1%) 0/2200 (0%)
Brain Cancer Metastatic 0/2197 (0%) 1/2200 (0%)
Brain Neoplasm 0/2197 (0%) 1/2200 (0%)
Breast Cancer 2/2197 (0.1%) 3/2200 (0.1%)
Cholangiocarcinoma 0/2197 (0%) 2/2200 (0.1%)
Chronic Lymphocytic Leukaemia 1/2197 (0%) 0/2200 (0%)
Colon Adenoma 0/2197 (0%) 1/2200 (0%)
Colon Cancer 1/2197 (0%) 6/2200 (0.3%)
Colon Neoplasm 1/2197 (0%) 0/2200 (0%)
Diffuse Large B-Cell Lymphoma 1/2197 (0%) 0/2200 (0%)
Endometrial Adenocarcinoma 0/2197 (0%) 1/2200 (0%)
Endometrial Cancer 1/2197 (0%) 0/2200 (0%)
Gastric Cancer 1/2197 (0%) 3/2200 (0.1%)
Gastric Neoplasm 0/2197 (0%) 1/2200 (0%)
Hepatic Neoplasm 0/2197 (0%) 1/2200 (0%)
Hepatocellular Carcinoma 3/2197 (0.1%) 0/2200 (0%)
Invasive Breast Carcinoma 0/2197 (0%) 1/2200 (0%)
Invasive Ductal Breast Carcinoma 1/2197 (0%) 2/2200 (0.1%)
Invasive Lobular Breast Carcinoma 0/2197 (0%) 1/2200 (0%)
Large Intestine Benign Neoplasm 0/2197 (0%) 1/2200 (0%)
Laryngeal Cancer 0/2197 (0%) 1/2200 (0%)
Lung Adenocarcinoma 1/2197 (0%) 0/2200 (0%)
Lung Cancer Metastatic 0/2197 (0%) 2/2200 (0.1%)
Lung Neoplasm 1/2197 (0%) 2/2200 (0.1%)
Lung Neoplasm Malignant 3/2197 (0.1%) 2/2200 (0.1%)
Malignant Melanoma 1/2197 (0%) 0/2200 (0%)
Malignant Neoplasm of Unknown Primary Site 1/2197 (0%) 1/2200 (0%)
Meningioma Malignant 0/2197 (0%) 1/2200 (0%)
Metastases to Bone 0/2197 (0%) 2/2200 (0.1%)
Metastases to Liver 2/2197 (0.1%) 2/2200 (0.1%)
Metastatic Renal Cell Carcinoma 0/2197 (0%) 1/2200 (0%)
Myelodysplastic Syndrome 0/2197 (0%) 1/2200 (0%)
Neuroendocrine Tumour 2/2197 (0.1%) 0/2200 (0%)
Non-Hodgkin's Lymphoma Stage Ii 1/2197 (0%) 0/2200 (0%)
Oesophageal Adenocarcinoma 0/2197 (0%) 1/2200 (0%)
Oropharyngeal Squamous Cell Carcinoma 1/2197 (0%) 0/2200 (0%)
Ovarian Cancer 1/2197 (0%) 0/2200 (0%)
Ovarian Endometrioid Carcinoma 0/2197 (0%) 1/2200 (0%)
Pancreatic Carcinoma 1/2197 (0%) 1/2200 (0%)
Pancreatic Carcinoma Metastatic 0/2197 (0%) 1/2200 (0%)
Pancreatic Neoplasm 0/2197 (0%) 1/2200 (0%)
Papillary Thyroid Cancer 1/2197 (0%) 1/2200 (0%)
Peritoneal Carcinoma Metastatic 1/2197 (0%) 0/2200 (0%)
Pituitary Tumour Benign 1/2197 (0%) 0/2200 (0%)
Plasma Cell Myeloma 1/2197 (0%) 0/2200 (0%)
Prostate Cancer 4/2197 (0.2%) 8/2200 (0.4%)
Prostatic Adenoma 0/2197 (0%) 2/2200 (0.1%)
Rectal Adenocarcinoma 1/2197 (0%) 1/2200 (0%)
Rectal Adenoma 0/2197 (0%) 1/2200 (0%)
Rectal Cancer 1/2197 (0%) 1/2200 (0%)
Rectosigmoid Cancer 1/2197 (0%) 0/2200 (0%)
Renal Cell Carcinoma 1/2197 (0%) 0/2200 (0%)
Renal Cell Carcinoma Stage I 1/2197 (0%) 0/2200 (0%)
Renal Neoplasm 1/2197 (0%) 0/2200 (0%)
Renal Oncocytoma 0/2197 (0%) 1/2200 (0%)
Salivary Gland Neoplasm 0/2197 (0%) 1/2200 (0%)
Squamous Cell Carcinoma 1/2197 (0%) 1/2200 (0%)
Squamous Cell Carcinoma of Lung 1/2197 (0%) 1/2200 (0%)
Squamous Cell Carcinoma of Skin 0/2197 (0%) 2/2200 (0.1%)
Squamous Cell Carcinoma of the Vulva 1/2197 (0%) 0/2200 (0%)
Tongue Neoplasm Malignant Stage Unspecified 1/2197 (0%) 0/2200 (0%)
Transitional Cell Cancer of Renal Pelvis and Ureter Metastatic 1/2197 (0%) 0/2200 (0%)
Transitional Cell Cancer of the Renal Pelvis and Ureter 0/2197 (0%) 2/2200 (0.1%)
Transitional Cell Carcinoma 0/2197 (0%) 3/2200 (0.1%)
Uterine Cancer 1/2197 (0%) 1/2200 (0%)
Uterine Leiomyoma 1/2197 (0%) 0/2200 (0%)
Nervous system disorders
Amputation Stump Pain 1/2197 (0%) 0/2200 (0%)
Basilar Migraine 1/2197 (0%) 1/2200 (0%)
Brain Injury 0/2197 (0%) 1/2200 (0%)
Brain Oedema 0/2197 (0%) 2/2200 (0.1%)
Carotid Artery Occlusion 1/2197 (0%) 1/2200 (0%)
Carotid Artery Stenosis 8/2197 (0.4%) 4/2200 (0.2%)
Carpal Tunnel Syndrome 0/2197 (0%) 2/2200 (0.1%)
Cauda Equina Syndrome 0/2197 (0%) 1/2200 (0%)
Cerebellar Haemorrhage 0/2197 (0%) 1/2200 (0%)
Cerebellar Infarction 1/2197 (0%) 0/2200 (0%)
Cerebellar Stroke 0/2197 (0%) 1/2200 (0%)
Cerebral Haematoma 1/2197 (0%) 1/2200 (0%)
Cerebral Haemorrhage 4/2197 (0.2%) 1/2200 (0%)
Cerebral Hypoperfusion 1/2197 (0%) 0/2200 (0%)
Cerebral Infarction 7/2197 (0.3%) 6/2200 (0.3%)
Cerebral Ischaemia 2/2197 (0.1%) 2/2200 (0.1%)
Cerebrovascular Accident 36/2197 (1.6%) 30/2200 (1.4%)
Cervical Radiculopathy 1/2197 (0%) 0/2200 (0%)
Chronic Inflammatory Demyelinating Polyradiculoneuropathy 0/2197 (0%) 1/2200 (0%)
Clonus 0/2197 (0%) 1/2200 (0%)
Dementia 1/2197 (0%) 2/2200 (0.1%)
Depressed Level of Consciousness 1/2197 (0%) 0/2200 (0%)
Diabetic Autonomic Neuropathy 0/2197 (0%) 1/2200 (0%)
Diabetic Hyperosmolar Coma 0/2197 (0%) 1/2200 (0%)
Diabetic Neuropathy 2/2197 (0.1%) 1/2200 (0%)
Dizziness 1/2197 (0%) 1/2200 (0%)
Dural Arteriovenous Fistula 1/2197 (0%) 0/2200 (0%)
Embolic Cerebral Infarction 0/2197 (0%) 1/2200 (0%)
Embolic Stroke 1/2197 (0%) 0/2200 (0%)
Encephalopathy 0/2197 (0%) 2/2200 (0.1%)
Epilepsy 1/2197 (0%) 0/2200 (0%)
Facial Paralysis 0/2197 (0%) 1/2200 (0%)
Generalised Tonic-Clonic Seizure 0/2197 (0%) 1/2200 (0%)
Haemorrhage Intracranial 1/2197 (0%) 1/2200 (0%)
Haemorrhagic Stroke 4/2197 (0.2%) 3/2200 (0.1%)
Haemorrhagic Transformation Stroke 0/2197 (0%) 1/2200 (0%)
Headache 1/2197 (0%) 1/2200 (0%)
Hemiparesis 1/2197 (0%) 0/2200 (0%)
Hypoglycaemic Coma 1/2197 (0%) 0/2200 (0%)
Hypoglycaemic Encephalopathy 1/2197 (0%) 0/2200 (0%)
Hypoxic-Ischaemic Encephalopathy 2/2197 (0.1%) 1/2200 (0%)
Intracranial Mass 0/2197 (0%) 1/2200 (0%)
Ischaemic Cerebral Infarction 1/2197 (0%) 0/2200 (0%)
Ischaemic Neuropathy 0/2197 (0%) 1/2200 (0%)
Ischaemic Stroke 17/2197 (0.8%) 14/2200 (0.6%)
Lacunar Infarction 4/2197 (0.2%) 4/2200 (0.2%)
Language Disorder 1/2197 (0%) 0/2200 (0%)
Lumbar Radiculopathy 1/2197 (0%) 1/2200 (0%)
Lumbosacral Radiculopathy 0/2197 (0%) 1/2200 (0%)
Metabolic Encephalopathy 0/2197 (0%) 1/2200 (0%)
Myelopathy 0/2197 (0%) 1/2200 (0%)
Paraesthesia 1/2197 (0%) 1/2200 (0%)
Paraparesis 0/2197 (0%) 1/2200 (0%)
Parkinson's Disease 0/2197 (0%) 1/2200 (0%)
Peripheral Sensorimotor Neuropathy 0/2197 (0%) 1/2200 (0%)
Piriformis Syndrome 1/2197 (0%) 0/2200 (0%)
Polyneuropathy 0/2197 (0%) 1/2200 (0%)
Presyncope 1/2197 (0%) 1/2200 (0%)
Progressive Supranuclear Palsy 1/2197 (0%) 0/2200 (0%)
Radicular Syndrome 1/2197 (0%) 0/2200 (0%)
Radiculopathy 2/2197 (0.1%) 0/2200 (0%)
Sciatica 1/2197 (0%) 0/2200 (0%)
Seizure 1/2197 (0%) 2/2200 (0.1%)
Somnolence 1/2197 (0%) 0/2200 (0%)
Spinal Cord Compression 0/2197 (0%) 1/2200 (0%)
Status Epilepticus 1/2197 (0%) 0/2200 (0%)
Syncope 3/2197 (0.1%) 4/2200 (0.2%)
Tension Headache 0/2197 (0%) 2/2200 (0.1%)
Thalamic Infarction 1/2197 (0%) 0/2200 (0%)
Transient Ischaemic Attack 4/2197 (0.2%) 10/2200 (0.5%)
Vascular Encephalopathy 2/2197 (0.1%) 1/2200 (0%)
Vasculitis Cerebral 0/2197 (0%) 1/2200 (0%)
Vertebral Artery Stenosis 1/2197 (0%) 0/2200 (0%)
Vith Nerve Paralysis 0/2197 (0%) 1/2200 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous 0/2197 (0%) 1/2200 (0%)
Retained Products of Conception 0/2197 (0%) 1/2200 (0%)
Product Issues
Device Malfunction 2/2197 (0.1%) 0/2200 (0%)
Psychiatric disorders
Affective Disorder 1/2197 (0%) 0/2200 (0%)
Completed Suicide 1/2197 (0%) 1/2200 (0%)
Confusional State 0/2197 (0%) 2/2200 (0.1%)
Delirium 3/2197 (0.1%) 1/2200 (0%)
Disorientation 1/2197 (0%) 0/2200 (0%)
Mental Status Changes 2/2197 (0.1%) 0/2200 (0%)
Substance-Induced Psychotic Disorder 0/2197 (0%) 1/2200 (0%)
Suicide Attempt 0/2197 (0%) 1/2200 (0%)
Renal and urinary disorders
Acute Kidney Injury 50/2197 (2.3%) 41/2200 (1.9%)
Anuria 0/2197 (0%) 1/2200 (0%)
Azotaemia 1/2197 (0%) 0/2200 (0%)
Bladder Cyst 0/2197 (0%) 1/2200 (0%)
Calculus Urinary 0/2197 (0%) 1/2200 (0%)
Chronic Kidney Disease 12/2197 (0.5%) 12/2200 (0.5%)
Diabetic Nephropathy 10/2197 (0.5%) 12/2200 (0.5%)
End Stage Renal Disease 23/2197 (1%) 16/2200 (0.7%)
Glomerulonephritis Chronic 1/2197 (0%) 0/2200 (0%)
Haematuria 3/2197 (0.1%) 1/2200 (0%)
Hydronephrosis 2/2197 (0.1%) 0/2200 (0%)
Nephrolithiasis 0/2197 (0%) 1/2200 (0%)
Nephropathy 4/2197 (0.2%) 1/2200 (0%)
Nephrotic Syndrome 1/2197 (0%) 2/2200 (0.1%)
Neurogenic Bladder 0/2197 (0%) 1/2200 (0%)
Renal Artery Stenosis 1/2197 (0%) 0/2200 (0%)
Renal Colic 0/2197 (0%) 1/2200 (0%)
Renal Failure 9/2197 (0.4%) 5/2200 (0.2%)
Renal Impairment 7/2197 (0.3%) 10/2200 (0.5%)
Renal Injury 0/2197 (0%) 1/2200 (0%)
Renal Tubular Necrosis 0/2197 (0%) 1/2200 (0%)
Stress Urinary Incontinence 0/2197 (0%) 1/2200 (0%)
Ureterolithiasis 0/2197 (0%) 1/2200 (0%)
Urethral Stenosis 1/2197 (0%) 1/2200 (0%)
Urinary Retention 1/2197 (0%) 2/2200 (0.1%)
Urinary Tract Obstruction 1/2197 (0%) 0/2200 (0%)
Reproductive system and breast disorders
Acquired Phimosis 1/2197 (0%) 0/2200 (0%)
Adenomyosis 0/2197 (0%) 1/2200 (0%)
Benign Prostatic Hyperplasia 4/2197 (0.2%) 3/2200 (0.1%)
Cervix Disorder 0/2197 (0%) 1/2200 (0%)
Cystocele 0/2197 (0%) 1/2200 (0%)
Erectile Dysfunction 1/2197 (0%) 0/2200 (0%)
Genital Swelling 1/2197 (0%) 0/2200 (0%)
Ovarian Cyst 0/2197 (0%) 1/2200 (0%)
Postmenopausal Haemorrhage 1/2197 (0%) 0/2200 (0%)
Prostatitis 1/2197 (0%) 1/2200 (0%)
Rectocele 0/2197 (0%) 1/2200 (0%)
Uterine Prolapse 0/2197 (0%) 1/2200 (0%)
Uterovaginal Prolapse 0/2197 (0%) 1/2200 (0%)
Vaginal Prolapse 0/2197 (0%) 1/2200 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Oedema 8/2197 (0.4%) 6/2200 (0.3%)
Acute Respiratory Distress Syndrome 1/2197 (0%) 1/2200 (0%)
Acute Respiratory Failure 6/2197 (0.3%) 5/2200 (0.2%)
Apnoeic Attack 1/2197 (0%) 0/2200 (0%)
Asthma 0/2197 (0%) 2/2200 (0.1%)
Bronchiectasis 0/2197 (0%) 1/2200 (0%)
Bronchitis Chronic 0/2197 (0%) 1/2200 (0%)
Bronchospasm 0/2197 (0%) 1/2200 (0%)
Chronic Obstructive Pulmonary Disease 16/2197 (0.7%) 9/2200 (0.4%)
Chronic Respiratory Failure 0/2197 (0%) 1/2200 (0%)
Cough 0/2197 (0%) 2/2200 (0.1%)
Dyspnoea 3/2197 (0.1%) 3/2200 (0.1%)
Dyspnoea at Rest 0/2197 (0%) 1/2200 (0%)
Emphysema 1/2197 (0%) 1/2200 (0%)
Epistaxis 2/2197 (0.1%) 0/2200 (0%)
Hiccups 1/2197 (0%) 0/2200 (0%)
Hydrothorax 1/2197 (0%) 1/2200 (0%)
Hypoxia 0/2197 (0%) 1/2200 (0%)
Laryngeal Haematoma 0/2197 (0%) 1/2200 (0%)
Nasal Polyps 1/2197 (0%) 0/2200 (0%)
Nasal Septum Perforation 1/2197 (0%) 0/2200 (0%)
Pickwickian Syndrome 1/2197 (0%) 0/2200 (0%)
Pleural Effusion 6/2197 (0.3%) 3/2200 (0.1%)
Pleuritic Pain 0/2197 (0%) 1/2200 (0%)
Pneumonia Aspiration 2/2197 (0.1%) 0/2200 (0%)
Pulmonary Arterial Hypertension 1/2197 (0%) 0/2200 (0%)
Pulmonary Congestion 1/2197 (0%) 1/2200 (0%)
Pulmonary Embolism 3/2197 (0.1%) 7/2200 (0.3%)
Pulmonary Fibrosis 0/2197 (0%) 4/2200 (0.2%)
Pulmonary Infarction 0/2197 (0%) 1/2200 (0%)
Pulmonary Mass 1/2197 (0%) 0/2200 (0%)
Pulmonary Oedema 7/2197 (0.3%) 3/2200 (0.1%)
Respiratory Depression 1/2197 (0%) 0/2200 (0%)
Respiratory Distress 1/2197 (0%) 0/2200 (0%)
Respiratory Failure 10/2197 (0.5%) 10/2200 (0.5%)
Sleep Apnoea Syndrome 1/2197 (0%) 0/2200 (0%)
Vocal Cord Leukoplakia 1/2197 (0%) 0/2200 (0%)
Skin and subcutaneous tissue disorders
Angioedema 1/2197 (0%) 2/2200 (0.1%)
Diabetic Foot 10/2197 (0.5%) 15/2200 (0.7%)
Diabetic Ulcer 0/2197 (0%) 1/2200 (0%)
Drug Eruption 0/2197 (0%) 1/2200 (0%)
Eczema 1/2197 (0%) 1/2200 (0%)
Erythema 0/2197 (0%) 1/2200 (0%)
Idiopathic Angioedema 1/2197 (0%) 0/2200 (0%)
Neuropathic Ulcer 0/2197 (0%) 1/2200 (0%)
Psoriasis 1/2197 (0%) 1/2200 (0%)
Rash Generalised 0/2197 (0%) 1/2200 (0%)
Skin Ulcer 8/2197 (0.4%) 18/2200 (0.8%)
Surgical and medical procedures
Hospitalisation 1/2197 (0%) 0/2200 (0%)
Vascular disorders
Accelerated Hypertension 0/2197 (0%) 1/2200 (0%)
Aortic Dissection 0/2197 (0%) 1/2200 (0%)
Aortic Stenosis 5/2197 (0.2%) 3/2200 (0.1%)
Arterial Disorder 0/2197 (0%) 1/2200 (0%)
Arterial Insufficiency 0/2197 (0%) 1/2200 (0%)
Arteriosclerosis 3/2197 (0.1%) 1/2200 (0%)
Circulatory Collapse 0/2197 (0%) 1/2200 (0%)
Deep Vein Thrombosis 7/2197 (0.3%) 2/2200 (0.1%)
Diabetic Vascular Disorder 2/2197 (0.1%) 0/2200 (0%)
Embolism 1/2197 (0%) 0/2200 (0%)
Embolism Arterial 2/2197 (0.1%) 0/2200 (0%)
Extremity Necrosis 8/2197 (0.4%) 9/2200 (0.4%)
Haematoma 1/2197 (0%) 2/2200 (0.1%)
Hypertension 7/2197 (0.3%) 7/2200 (0.3%)
Hypertensive Crisis 9/2197 (0.4%) 9/2200 (0.4%)
Hypertensive Emergency 2/2197 (0.1%) 1/2200 (0%)
Hypotension 3/2197 (0.1%) 4/2200 (0.2%)
Intermittent Claudication 0/2197 (0%) 1/2200 (0%)
Leriche Syndrome 0/2197 (0%) 1/2200 (0%)
Lymphoedema 1/2197 (0%) 0/2200 (0%)
Necrosis Ischaemic 1/2197 (0%) 0/2200 (0%)
Orthostatic Hypotension 5/2197 (0.2%) 2/2200 (0.1%)
Peripheral Arterial Occlusive Disease 11/2197 (0.5%) 10/2200 (0.5%)
Peripheral Artery Occlusion 0/2197 (0%) 2/2200 (0.1%)
Peripheral Ischaemia 5/2197 (0.2%) 3/2200 (0.1%)
Peripheral Vascular Disorder 1/2197 (0%) 5/2200 (0.2%)
Peripheral Venous Disease 0/2197 (0%) 1/2200 (0%)
Post Thrombotic Syndrome 1/2197 (0%) 0/2200 (0%)
Shock Haemorrhagic 0/2197 (0%) 1/2200 (0%)
Subclavian Artery Stenosis 0/2197 (0%) 1/2200 (0%)
Thrombophlebitis Superficial 2/2197 (0.1%) 2/2200 (0.1%)
Thrombosis 0/2197 (0%) 1/2200 (0%)
Vascular Occlusion 0/2197 (0%) 1/2200 (0%)
Venous Haemorrhage 1/2197 (0%) 0/2200 (0%)
Venous Thrombosis Limb 1/2197 (0%) 0/2200 (0%)
Other (Not Including Serious) Adverse Events
Placebo Canagliflozin 100 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1447/2197 (65.9%) 1320/2200 (60%)
Blood and lymphatic system disorders
Anaemia 136/2197 (6.2%) 77/2200 (3.5%)
Ear and labyrinth disorders
Vertigo 50/2197 (2.3%) 46/2200 (2.1%)
Eye disorders
Cataract 80/2197 (3.6%) 58/2200 (2.6%)
Diabetic Retinopathy 55/2197 (2.5%) 65/2200 (3%)
Gastrointestinal disorders
Constipation 82/2197 (3.7%) 80/2200 (3.6%)
Diarrhoea 105/2197 (4.8%) 91/2200 (4.1%)
Nausea 52/2197 (2.4%) 54/2200 (2.5%)
Vomiting 48/2197 (2.2%) 41/2200 (1.9%)
General disorders
Oedema Peripheral 199/2197 (9.1%) 119/2200 (5.4%)
Infections and infestations
Bronchitis 86/2197 (3.9%) 83/2200 (3.8%)
Gastroenteritis 51/2197 (2.3%) 49/2200 (2.2%)
Influenza 88/2197 (4%) 87/2200 (4%)
Nasopharyngitis 133/2197 (6.1%) 130/2200 (5.9%)
Onychomycosis 33/2197 (1.5%) 45/2200 (2%)
Pneumonia 52/2197 (2.4%) 41/2200 (1.9%)
Respiratory Tract Infection 44/2197 (2%) 19/2200 (0.9%)
Upper Respiratory Tract Infection 117/2197 (5.3%) 90/2200 (4.1%)
Urinary Tract Infection 185/2197 (8.4%) 202/2200 (9.2%)
Injury, poisoning and procedural complications
Limb Injury 45/2197 (2%) 43/2200 (2%)
Investigations
Blood Creatinine Increased 185/2197 (8.4%) 140/2200 (6.4%)
Glomerular Filtration Rate Decreased 80/2197 (3.6%) 63/2200 (2.9%)
Metabolism and nutrition disorders
Diabetes Mellitus 44/2197 (2%) 24/2200 (1.1%)
Hyperglycaemia 74/2197 (3.4%) 54/2200 (2.5%)
Hyperkalaemia 152/2197 (6.9%) 129/2200 (5.9%)
Hyperuricaemia 75/2197 (3.4%) 64/2200 (2.9%)
Hypoglycaemia 227/2197 (10.3%) 213/2200 (9.7%)
Musculoskeletal and connective tissue disorders
Arthralgia 83/2197 (3.8%) 81/2200 (3.7%)
Back Pain 99/2197 (4.5%) 94/2200 (4.3%)
Pain in Extremity 54/2197 (2.5%) 56/2200 (2.5%)
Nervous system disorders
Diabetic Neuropathy 69/2197 (3.1%) 56/2200 (2.5%)
Headache 65/2197 (3%) 69/2200 (3.1%)
Renal and urinary disorders
Acute Kidney Injury 51/2197 (2.3%) 50/2200 (2.3%)
End Stage Renal Disease 52/2197 (2.4%) 30/2200 (1.4%)
Renal Impairment 61/2197 (2.8%) 42/2200 (1.9%)
Respiratory, thoracic and mediastinal disorders
Cough 81/2197 (3.7%) 80/2200 (3.6%)
Dyspnoea 46/2197 (2.1%) 35/2200 (1.6%)
Skin and subcutaneous tissue disorders
Skin Ulcer 70/2197 (3.2%) 85/2200 (3.9%)
Vascular disorders
Hypertension 193/2197 (8.8%) 144/2200 (6.5%)
Hypotension 30/2197 (1.4%) 57/2200 (2.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.

Results Point of Contact

Name/Title Senior Director
Organization Janssen Research & Development, LLC
Phone 844-434-4210
Email ClinicalTrialDisclosure@its.jnj.com
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02065791
Other Study ID Numbers:
  • CR103517
  • 2013-004494-28
  • 28431754DNE3001
First Posted:
Feb 19, 2014
Last Update Posted:
Dec 5, 2019
Last Verified:
Dec 1, 2019