Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source (RE-SPECT ESUS)

Sponsor

Boehringer Ingelheim (Industry)

Overall Status

Completed

CT.gov ID

NCT02239120

Collaborator

(none)

5,390

Enrollment

569

Locations

Arms

44.6

Actual Duration (Months)

9.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial will enroll approximately 6,000 patients with recent embolic stroke of unknown source (ESUS). Patients will be randomized to dabigatran or acetylsalicyclic acid (ASA) (1:1 ratio) and have visits every three months. The study doctor may prescribe blinded concomitant ASA for pts with coronary artery disease but this is not mandatory. All Adverse Events (AEs), Serious Adverse Events (SAEs), outcome events will be recorded. The trial will conclude when the required number of stroke events are positively adjudicated which is estimated to take 3 years (including 2.5 years of enrollment).

Condition or Disease	Intervention/Treatment	Phase
Stroke Secondary Prevention	Drug: optional ASA as comedication Drug: placebo to ASA Drug: placebo to optional ASA as comedication Drug: placebo to dabigatran etexilate Drug: ASA 100 mg Drug: dabigatran etexilate	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

5390 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

Randomized, Double-blind, Evaluation in Secondary Stroke Prevention Comparing the EfficaCy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate (110 mg or 150 mg, Oral b.i.d.) Versus Acetylsalicylic Acid (100 mg Oral q.d.) in Patients With Embolic Stroke of Undetermined Source (RESPECT ESUS)

Actual Study Start Date :

Nov 27, 2014

Actual Primary Completion Date :

Aug 14, 2018

Actual Study Completion Date :

Aug 14, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: dabigatran etexilate 110 or 150 mg Patients will be assigned Dabigatran 150 mg b.i.d. (unless they are 75 years or older, or have a Creatinine Clearance (CrCl) of greater than or equal to 30 to less than 50ml/min (or experience GI bleed during trial), in which case they will receive Dabigatran 110 mg b.i.d.). All patients in this arm will also receive ASA placebo (q.d.)	Drug: optional ASA as comedication optional concomitant treatment which can be used for patients with coronary artery disease. It is not required for these pts. Drug: placebo to ASA placebo to comparator drug Drug: dabigatran etexilate active drug
Active Comparator: ASA 100 mg All patients will receive blinded ASA 100 mg q.d. and dabigatran placebo 150 mg b.i.d. (unless they are 75 years or older, or have a CrCl of greater than or equal to 30 to less than 50ml/min (or experience GI bleed during trial), in which case they will receive placebo Dabigatran 110 mg b.i.d	Drug: placebo to optional ASA as comedication optional concomitant treatment which can be used for patients with coronary artery disease. It is not required for these pts. Drug: placebo to dabigatran etexilate placebo Drug: ASA 100 mg active comparator drug

Arm

Intervention/Treatment

Experimental: dabigatran etexilate 110 or 150 mg

Patients will be assigned Dabigatran 150 mg b.i.d. (unless they are 75 years or older, or have a Creatinine Clearance (CrCl) of greater than or equal to 30 to less than 50ml/min (or experience GI bleed during trial), in which case they will receive Dabigatran 110 mg b.i.d.). All patients in this arm will also receive ASA placebo (q.d.)

Drug: optional ASA as comedication

optional concomitant treatment which can be used for patients with coronary artery disease. It is not required for these pts.

Drug: placebo to ASA

placebo to comparator drug

Drug: dabigatran etexilate

active drug

Active Comparator: ASA 100 mg

All patients will receive blinded ASA 100 mg q.d. and dabigatran placebo 150 mg b.i.d. (unless they are 75 years or older, or have a CrCl of greater than or equal to 30 to less than 50ml/min (or experience GI bleed during trial), in which case they will receive placebo Dabigatran 110 mg b.i.d

Drug: placebo to optional ASA as comedication

optional concomitant treatment which can be used for patients with coronary artery disease. It is not required for these pts.

Drug: placebo to dabigatran etexilate

placebo

Drug: ASA 100 mg

active comparator drug

Outcome Measures

Primary Outcome Measures

Adjudicated Recurrent Stroke [From randomisation until full follow up period, approximately 43 months.]
Adjudicated recurrent stroke (ischemic, hemorrhagic, or unspecified) is presented. The annualised event rate represents the average number of events per patient during a 1-year period.
First Major Bleed (Adjudicated) [Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.]
First major bleed is primary safety endpoint. Major bleeds were defined according to the International Society of Thrombosis and Haemostasis (ISTH) definition as follows: Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome and/or, Bleeding (which should be overt) associated with a reduction in haemoglobin of at least 2 grams/ decilitre (g/dL) (1.24 millimoles Per Litre (mmol/L)), or leading to transfusion of ≥2 units of blood or packed cells (equivalent to ≥4.5 units in Japan); the haemoglobin drop should be considered to be due to and temporally related to the bleeding event and/or, Fatal bleed. The annualised event rate represents the average number of events per patient during a 1-year period.

Secondary Outcome Measures

Adjudicated Ischaemic Stroke [From randomisation until full follow up period, up to 43 months]
Adjudicated ischaemic stroke is a key secondary endpoint. The annualised event rate represents the average number of events per patient during a 1-year period.
Adjudicated Composite of Non-fatal Stroke, Non-fatal Myocardial Infarction, or Cardiovascular Death [From randomisation until full follow up period, up to 43 months]
Adjudicated composite of non-fatal stroke, non-fatal myocardial infarction (MI), or cardiovascular death is a key secondary endpoint. The annualised event rate represents the average number of events per patient during a 1-year period.
Disabling Stroke [From randomisation until full follow up period, up to 43 months]
Disabling stroke (modified Rankin Scale greater than or equal to 4, as determined 3 months after recurrent stroke) is presented. The annualised event rate represents the average number of events per patient during a 1-year period.
All-cause Death [From randomisation until full follow up period, up to 43 months]
All-cause death is presented. The annualised event rate represents the average number of events per patient during a 1-year period.
Adjudicated Intracranial Hemorrhage [Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.]
Adjudicated intracranial haemorrhage comprised the subtypes of intracerebral bleeds, intraventricular bleeds, subdural bleeds, epidural bleeds, and subarachnoid bleeds. Microbleeds did not qualify as intracranial haemorrhage, except when they were symptomatic. The annualised event rate represents the average number of events per patient during a 1-year period.
Adjudicated Fatal Bleed [Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.]
Adjudicated fatal bleeding was defined as a bleeding event which the Independent Event Adjudication Committee (IAC) determined as the primary cause of death or contributed directly to death. The annualised event rate represents the average number of events per patient during a 1-year period. Because there were 0 events in one treatment group, the hazard ratio is unable to be calculated.
Adjudicated Life-threatening Bleed [Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.]
Major bleeds were to be classified as life-threatening if they met one or more of the following criteria: fatal bleed, symptomatic intracranial bleed, reduction in haemoglobin of at least 5 grams/ deciliter (g/dL), transfusion of at least 4 units of packed red blood cells (equivalent to 9 units in Japan), associated with hypotension requiring the use of intravenous inotropic agents, or necessitated surgical intervention. The annualised event rate represents the average number of events per patient during a 1-year period.
Any Bleed (Investigator-reported) [Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.]
This was the sum of all major and minor bleeds (Minor bleeds were clinical bleeds that did not fulfil the criteria for major bleeds), regardless of severity. The annualised event rate represents the average number of events per patient during a 1-year period.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 150 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Ischemic stroke with a brain lesion visualized by neuroimaging (either brain Computed Tomography (CT) or Magnetic Resonance Image (MRI)). The visualized stroke is a non-lacunar infarct , e.g. involving the cortex or >1.5 cm (>2.0 cm if measured on MRI diffusion-weighted images) in largest diameter if exclusively subcortical.Visualization by CT usually requires delayed imaging >24-48 hours after stroke onset.
The index stroke must have occurred either up to 3 months before randomization (Modified Rankin Scale(mRS) <=3 at randomization) or up to 6 months before randomization (mRS <=3 at randomization) in selected patients that are >= 60 years plus at least one additional risk factor for recurrent stroke.
Arterial imaging or cervical plus Transcranial Doppler (TCD) ultrasonography does not show extra-cranial or intracranial atherosclerosis with >= 50% luminal stenosis in artery supplying the area of acute ischemia.
As evidenced by cardiac monitoring for >= 20 hours with automated rhythm detection, there is absence of AF > 6 minutes in duration (within a 20 hour period, either as single episode or cumulative time of multiple episodes).

Further inclusion criteria apply.

Exclusion criteria:

Modified Rankin Scale of >=4 at time of randomization or inability to swallow medications.
Major risk cardioembolic source of embolism such as: a) intracardiac thrombus as evidenced by transthoracic or transesophageal echocardiography, b) paroxysmal, persistent or permanent Atrial fibrillation (AF), c) atrial flutter, d) prosthetic cardiac valve (mitral or aortic, bioprosthetic or mechanical), e) atrial myxoma, f) other cardiac tumors, g) moderate or severe mitral stenosis, h) recent (< 4weeks) myocardial infarction, i) valvular vegetations, or j) infective endocarditis.
Any indication that requires treatment with an anticoagulant as per Investigator's judgment.
History of atrial fibrillation (unless it was due to reversible causes such as hyperthyroidism or binge drinking, and has been permanently resolved).
Other specific stroke etiology (i.e. cerebral arteritis or arterial dissection, migraine with aura/vasospasm, drug abuse).
Renal impairment with estimated creatinine clearance (as calculated by Cockcroft-Gault equation) <30mL/min at screening, or where Investigator expects creatinine clearance is likely to drop below 30mL/min during the course of the study.

Further exclusion criteria apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bronislava Shafran, MD PC	Phoenix	Arizona	United States	85006
2	Westside Medical Associates of Los Angeles	Beverly Hills	California	United States	90211
3	TriWest Research Associates, LLC	El Cajon	California	United States	92020
4	University of California	Fresno	California	United States	93721
5	Glendale Adventist Medical Center	Glendale	California	United States	91206
6	Collaborative Neuroscience Network, LLC (CNS)	Long Beach	California	United States	90806
7	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
8	University of California Los Angeles	Los Angeles	California	United States	90095
9	Huntington Hospital	Pasadena	California	United States	91105
10	University of California	San Diego	California	United States	92103
11	University of California	San Francisco	California	United States	94143
12	University of Colorado Denver	Aurora	Colorado	United States	80045
13	Colorado Neurological Institute	Englewood	Colorado	United States	80113
14	University of Colorado Denver	Fort Collins	Colorado	United States	80528
15	St. Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81501
16	Hartford Hospital	Hartford	Connecticut	United States	06102
17	JEM Research Institute	Atlantis	Florida	United States	33462
18	Boca Raton Regional Hospital	Boca Raton	Florida	United States	33486
19	Tenet Florida Physician Services	Boynton Beach	Florida	United States	33472
20	Nova Clinical Research, LLC	Bradenton	Florida	United States	34209
21	Broward Health North	Deerfield Beach	Florida	United States	33064
22	Center for Advanced Research Excellence	Hialeah	Florida	United States	33016
23	Bruce W. Carter, Miami VA Healthcare System	Miami	Florida	United States	33125
24	University of Miami	Miami	Florida	United States	33136
25	Bay Neurological Institute	Panama City	Florida	United States	32405
26	Carol L Pappas, MD PhD PA	Saint Petersburg	Florida	United States	33713
27	University of South Florida	Tampa	Florida	United States	33606
28	Vero Beach Neurology and Research Institute	Vero Beach	Florida	United States	32960
29	Palm Beach Neuroscience Institute	West Palm Beach	Florida	United States	33409
30	Augusta University	Augusta	Georgia	United States	30912
31	WellStar Medical Group - Neurosurgery	Marietta	Georgia	United States	30060
32	The Queen's Medical Center	Honolulu	Hawaii	United States	96813
33	Saint Alphonsus Medical Center-Neurology	Boise	Idaho	United States	83704
34	Northwest Heart Clinical Research, LLC	Arlington Heights	Illinois	United States	60005
35	Northwestern University	Chicago	Illinois	United States	60611
36	Rush University Medical Center	Chicago	Illinois	United States	60612
37	University of Chicago	Chicago	Illinois	United States	60637
38	Medicoricium, LLC	Fairview Heights	Illinois	United States	62208
39	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
40	Quincy Physicians and Surgeons Clinic, S.C.	Quincy	Illinois	United States	62301
41	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
42	Community Clinical Research Center	Anderson	Indiana	United States	46011
43	Ruan Neurology Clinic and Research Center	Des Moines	Iowa	United States	50314
44	Associates in Neurology, PSC	Lexington	Kentucky	United States	40513
45	University of Louisville	Louisville	Kentucky	United States	40202
46	Alexandria Cardiology Clinic	Alexandria	Louisiana	United States	71301
47	Culicchia Neurological Clinic	Marrero	Louisiana	United States	70072
48	Tulane University Hospital and Clinic	New Orleans	Louisiana	United States	70112
49	Ochsner Medical Center	New Orleans	Louisiana	United States	70121
50	Anne Arundel Medical Center	Annapolis	Maryland	United States	21401
51	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
52	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
53	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
54	Newton-Wellesley Hospital	Newton	Massachusetts	United States	02462
55	Henry Ford Health System	Detroit	Michigan	United States	48202
56	McLaren Flint	Flint	Michigan	United States	48532
57	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
58	Spectrum Health Medical Center	Grand Rapids	Michigan	United States	49503
59	Sparrow Clinical Research Institute	Lansing	Michigan	United States	48912
60	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
61	The Duluth Clinic dba Essentia Health Duluth Clinic	Duluth	Minnesota	United States	55805
62	Abbott Northwestern Hospital, Radiology Department	Minneapolis	Minnesota	United States	55407
63	HealthPartners Neuroscience Center	Saint Paul	Minnesota	United States	55130
64	Jackson Heart Clinic, P.A.	Jackson	Mississippi	United States	39216
65	Boone Hospital Center	Columbia	Missouri	United States	65201
66	University of Missouri Health System	Columbia	Missouri	United States	65201
67	SSM Health St. Clare Hospital	Fenton	Missouri	United States	63026
68	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
69	Saint Louis University	Saint Louis	Missouri	United States	63104
70	St. Louis Heart and Vascular, P.C.	Saint Louis	Missouri	United States	63136
71	The Nebraska Medical Center	Omaha	Nebraska	United States	68198
72	Renown Institute for Neurosciences	Reno	Nevada	United States	89502
73	NYC Health + Hospitals/Coney Island	Brooklyn	New York	United States	11235
74	New York Presbyterian Hudson Valley Hospital	Cortlandt Manor	New York	United States	10567
75	UHS Wilson Medical Center,Office of Clin Trials	Johnson City	New York	United States	13790
76	North Shore University Hospital	Manhasset	New York	United States	11030
77	Winthrop University Hospital	Mineola	New York	United States	11501
78	Mount Sinai Beth Israel	New York	New York	United States	10003
79	Novant Health Neurology Specialists	Charlotte	North Carolina	United States	28207
80	Duke Clinic 1L	Durham	North Carolina	United States	27710
81	Cone Health System	Greensboro	North Carolina	United States	27401
82	Novant Health Neurology Hickory	Hickory	North Carolina	United States	28602
83	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
84	Altru Health System	Grand Forks	North Dakota	United States	58201
85	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
86	Holzer Clinic LLC	Gallipolis	Ohio	United States	45631
87	Advanced Neurology Associates	Youngstown	Ohio	United States	44504
88	Oregon Health and Sciences University	Portland	Oregon	United States	97239
89	Veterans Affairs Portland Health Care System	Portland	Oregon	United States	97239
90	Sacred Heart Medical Center at RiverBend	Springfield	Oregon	United States	97477
91	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
92	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
93	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
94	Abington Neurological Associates	Willow Grove	Pennsylvania	United States	19090
95	Rhode Island Hospital	Providence	Rhode Island	United States	02903
96	Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
97	Methodist University Hospital	Memphis	Tennessee	United States	38105
98	Centennial Heart Cardiovascular Consultants, LLC	Nashville	Tennessee	United States	37203
99	Saint Thomas Health	Nashville	Tennessee	United States	37205
100	Seton Medical Center Austin	Austin	Texas	United States	78705
101	Houston Methodist Hospital	Houston	Texas	United States	77030
102	Bhupesh Dihenia, M.D.,P.A.	Lubbock	Texas	United States	79410
103	University of Vermont	Burlington	Vermont	United States	05401
104	Virginia Commonwealth University	Richmond	Virginia	United States	23298
105	Carilion Riverside	Roanoke	Virginia	United States	24016
106	Virginia Mason Medical Center	Seattle	Washington	United States	98101
107	Swedish Neuroscience Institute	Seattle	Washington	United States	98122
108	Marshall University	Huntington	West Virginia	United States	25701
109	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
110	University of Wisconsin	Madison	Wisconsin	United States	53792
111	STAT Research	Caba		Argentina	C1023AAB
112	Fundación Favaloro	Caba		Argentina	C1093AAS
113	Hospital Italiano de Buenos Aires	Caba		Argentina	C1199ABD
114	Instituto Médico DAMIC S.R.L.	Cordoba		Argentina	X5003DCE
115	Clinica Coronel Suarez SA	Coronel Suarez		Argentina	B7540DOL
116	Hospital Privado de Comunidad	Mar del Plata		Argentina	B7600CBM
117	Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia	2050
118	St Vincent's Hospital Sydney	Darlinghurst	New South Wales	Australia	2010
119	Kanwal Medical Complex	Kanwal	New South Wales	Australia	2259
120	John Hunter Hospital	New Lambton	New South Wales	Australia	2305
121	Royal North Shore Hospital	St Leonards	New South Wales	Australia	2038
122	Sunshine Coast University Hospital	Birtinya	Queensland	Australia	4575
123	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
124	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
125	Calvary North Adelaide Hospital	Adelaide	South Australia	Australia	5001
126	Box Hill Hospital	Box Hill	Victoria	Australia	3128
127	Austin Health	Heidelberg	Victoria	Australia	3084
128	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
129	Alfred Health	Victoria		Australia	3004
130	LKH-Univ. Hospital Graz	Graz		Austria	8036
131	Medical University of Innsbruck	Innsbruck		Austria	6020
132	Kepler Univ. Klinikum Linz	Linz		Austria	4020
133	Kepler Univ. Klinikum Linz	Linz		Austria	4021
134	KH d. Barmherzigen Brüder Linz, Neurologie	Linz		Austria	4021
135	Universitätsklinikum Tulln, Abteilung für Neurologie	Tulln		Austria	3430
136	Hosp.Hietzing with Neuro.Centr Rosenhuegel,II Neuro.dep,Wien	Vienna		Austria	1130
137	Wilhelminenspital	Wien		Austria	1160
138	Aalst - HOSP Onze-Lieve-Vrouw	Aalst		Belgium	9300
139	Arlon - HOSP Sud Luxembourg - Vivalia	Arlon		Belgium	6700
140	AZ Sint-Jan Brugge	Brugge		Belgium	3000
141	Brussels-UNIV Brugmann -Horta	Brussel		Belgium	1020
142	Brussels - HOSP Europe (Ste-Elisabeth)	Brussel		Belgium	1180
143	Brussels - UNIV Saint-Luc	Bruxelles		Belgium	1200
144	UNIV UZ Gent	Gent		Belgium	9000
145	Kortrijk - HOSP AZ Groeninge Kennedylaan	Kortrijk		Belgium	8500
146	UZ Leuven	Leuven		Belgium	3000
147	Liège - HOSP St-Joseph	Liège		Belgium	4000
148	Roeselare - HOSP AZ Delta	Roeselare		Belgium	8800
149	Rumst - HOSP AZ Heilige Familie	Rumst		Belgium	2840
150	Sint-Truiden - HOSP St-Trudo (St-Jozef)	Sint-Truiden		Belgium	3800
151	Wilrijk - HOSP GZA (St-Augustinus)	Wilrijk		Belgium	2610
152	Yvoir - UNIV UCL de Mont-Godinne	Yvoir		Belgium	5530
153	Hospital Clinicas de Botucatu	Botucatu		Brazil	18618-000
154	Instituto de Medicina Flumignano	Curitiba		Brazil	80050-250
155	Clinica Neurologica e Neurocirurgica de Joinvile	Joinvile		Brazil	89202-165
156	Hospital de Clínicas de Porto Alegre	Porto Alegre		Brazil	90035-903
157	H.C.da Fac. de Medicina de Ribeirao Preto	Ribeirao Preto		Brazil	14048-900
158	Hospital Quinta D¿Or	Rio de Janeiro		Brazil
159	Foothills Medical Centre	Calgary	Alberta	Canada	T2N 2T9
160	University of Alberta Hospital (University of Alberta)	Edmonton	Alberta	Canada	T6G 2B7
161	Grey Nuns Hospital	Edmonton	Alberta	Canada	T6L 5X8
162	Prairie Mountain Health	Brandon	Manitoba	Canada	R7A 2B3
163	Hopital Notre-Dame du CHUM	Montreal	Migration Data	Canada	H2L 4M1
164	Jewish General Hospital	Montreal	Migration Data	Canada	H3T 1E2
165	Saint John Regional Hospital	Saint John	New Brunswick	Canada	E2L 4L2
166	Eastern Health (MUN)	St. John's	Newfoundland and Labrador	Canada	A1B 3V6
167	Victoria Hospital (LHSC)	London	Ontario	Canada	N6A 5A5
168	St. Michael's Hospital	Toronto	Ontario	Canada	M5C 1R6
169	Toronto Western Hospital	Toronto	Ontario	Canada	M5T 2S8
170	CSSS de Chicoutimi	Chicoutimi	Quebec	Canada	G7H 5H6
171	Hopital Charles - LeMoyne	Greenfield Park	Quebec	Canada	J4V 2H1
172	Montreal General Hospital - McGill University Health Centre	Montreal	Quebec	Canada	H3G 1A4
173	CHUS Fleurimont	Sherbrooke	Quebec	Canada	J1H 5N4
174	St Jerome Medical Research Inc.	St-Jerome	Quebec	Canada	J7Z 5T3
175	CHU de Quebec-Universite Laval Research Centre	Quebec		Canada	G1J 1Z4
176	Clínica Alemana de Santiago S.A.	Santiago		Chile	7650568
177	Clínica Dávila	Santiago		Chile
178	Clinica Alemana de Temuco	Temuco		Chile
179	Beijing Tiantan Hospital affiliated to Cap Med University	Beijing		China	100050
180	Peking University Third Hospital	Beijing		China	100191
181	First Hospital of Jilin University	Changchun		China	130021
182	First Affiliated Hospital of Guangzhou Medical University	Guangzhou		China	510000
183	First Affiliated Hospital of Guangzhou University of TCM	Guangzhou		China	510000
184	The First Affiliated Hospital of Jinan University	Guangzhou		China	510630
185	The Affiliated Hospital of Guizhou Medical University	Guiyang		China	550000
186	2nd Affiliated Hosp Zhejiang University College of Medical	Hangzhou		China	310009
187	Zhejiang Hospital	Hangzhou		China	310013
188	The Affiliated Hospital of Hangzhou Normal University	Hangzhou		China	310015
189	Zhejiang University School of Medicine SIR RUN RUN SHAW Hospital	Hangzhou		China	310016
190	Jinlin Central Hospital	Jilin		China	132602
191	The Second Affiliated Hospital to Nanchang University	Nanchang		China	330006
192	Nanjing Drum Tower Hospital	Nanjing		China	210008
193	Zhongda Hospital Southeast University	Nanjing		China	210009
194	QingDao Municipal Hospital	Qingdao		China	266071
195	The affiliated hospital of medicalcollege qingdao university	Qingdao		China	266555
196	Huashan Hospital, Fudan University	Shanghai		China	200040
197	Tongji Hospital, Tongji University	Shanghai		China	200065
198	General Hospital of Shenyang Military Region	Shenyang		China	110016
199	First Affiliated Hospital of Xiamen University	Xiamen		China	361003
200	Affiliated Hospital, Xuzhou Medical college	Xuzhou		China	221002
201	Servicios Médicos Muñoz Solano	Bogotá		Colombia
202	Sociedad de Cirugia de Bogota Hospital de San José	Bogotá		Colombia
203	Fundación Valle del Lili	Cali		Colombia
204	Fundación Cardiovascular de Colombia	Floridablanca		Colombia
205	General Hospital Varazdin	Varazdin		Croatia	42000
206	Clin.Hosp.Centre Zagreb,Cerebrovascul.disease w/ intens.care	Zagreb		Croatia	10 000
207	University hospital center Zagreb	Zagreb		Croatia	10 000
208	Univ. Hosp. Sisters of Mercy, Neurology Clinic, Zagreb	Zagreb		Croatia	100 00
209	Cerebrovascular site, private prac., Brno	Brno		Czechia	60200
210	Hospital Jihlava	Jihlava		Czechia	58633
211	University Hospital Olomouc	Olomouc		Czechia	77900
212	Cerebrovascular site, Ostrava	Ostrava		Czechia	70300
213	Cerebrovascular site, Ostrava	Ostrava		Czechia	70800
214	Hospital Homolka, Prague	Prague 5		Czechia	15006
215	University Hospital Motol	Praha 5		Czechia	150 06
216	East Estonia Central Hospital, Neurology Dept, Ahtme	Ahtme		Estonia	31025
217	West Tallinn Central Hospital, Neurology Dept.	Tallinn		Estonia	10617
218	North Estonia Medical Centre Foundation, Tallin	Tallinn		Estonia	13419
219	Tartu University Hospital	Tartu		Estonia	51014
220	HOP Pays d'Aix	Aix en Provence		France	13616
221	HOP de Bayonne	Bayonne		France	64109
222	HOP Jean Minjoz	Besançon		France	25030
223	HOP Pellegrin	Bordeaux		France	33076
224	HOP de la Cavale Blanche	Brest		France	29609
225	HOP Pierre Wertheimer	Bron		France	69677
226	HOP Côte de Nacre	Caen		France	14033
227	HOP Grenoble, Neuro, Grenoble	Grenoble		France	38043
228	HOP Roger Salengro	Lille		France	59037
229	HOP Mercy	Metz		France	57085
230	HOP Paris Saint-Joseph	Paris		France	75014
231	GHU Paris Psychiatrie et Neurosciences	Paris		France	75674
232	HOP Purpan	Toulouse		France	31059
233	Klinikum Altenburger Land GmbH	Altenburg		Germany	04600
234	Neurologische Klinik GmbH, Bad Neustadt	Bad Neustadt		Germany	97616
235	Vivantes Netzwerk für Gesundheit GmbH	Berlin		Germany	12351
236	Evangelisches Klinikum Bethel gGmbH	Bielefeld		Germany	33611
237	Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH	Bochum		Germany	44789
238	St. Josef- und St. Elisabeth-Hospital gGmbH	Bochum		Germany	44791
239	Gesundheit Nord gGmbH \| Klinikverbund Bremen	Bremen		Germany	28177
240	Klinikum Bremerhaven	Bremen		Germany	28755
241	Krankenhäuser Buchholz und Winsen gGmbH	Buchholz		Germany	21244
242	Allgemeines Krankenhaus, Celle	Celle		Germany	29223
243	Klinikum Chemnitz gGmbH	Chemnitz		Germany	09131
244	Klinikum Coburg gGmbH	Coburg		Germany	96450
245	Klinikzentrum Mitte, Dortmund	Dortmund		Germany	44137
246	Städtisches Klinikum Dresden	Dresden		Germany	01067
247	Universitätsklinikum Carl Gustav Carus Dresden	Dresden		Germany	01307
248	Universitätsklinikum Düsseldorf	Düsseldorf		Germany	40225
249	Marien-Hospital, Düsseldorf	Düsseldorf		Germany	40479
250	Universitätsklinikum Erlangen	Erlangen		Germany	91054
251	Alfried Krupp Krankenhaus Essen	Essen		Germany	45131
252	Universitätsklinikum Essen AöR	Essen		Germany	45147
253	Universitätsklinikum Frankfurt	Frankfurt am Main		Germany	60528
254	Klinikum Frankfurt Höchst GmbH	Frankfurt		Germany	65929
255	Klinikum Friedrichshafen	Friedrichshafen		Germany	88048
256	Klinikum Fulda gAG	Fulda		Germany	36043
257	Evangelische Klinik Gelsenkirchen	Gelsenkirchen		Germany	45879
258	SRH Wald-Klinikum Gera GmbH	Gera		Germany	07548
259	Universitätsklinikum Gießen und Marburg GmbH	Gießen		Germany	35385
260	Universitätsmedizin Greifswald	Greifswald		Germany	17475
261	Bezirkskrankenhaus, Günzburg	Günzburg		Germany	89312
262	Asklepios Klinik St. Georg	Hamburg		Germany	20099
263	Universitätsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246
264	Asklepios Klinik Harburg	Hamburg		Germany	21075
265	Asklepios Klinik Wandsbek	Hamburg		Germany	22043
266	Asklepios Klinik Barmbek	Hamburg		Germany	22291
267	Asklepios Klinik Altona	Hamburg		Germany	22763
268	Klinikum Hanau GmbH	Hanau		Germany	63450
269	Medizinische Hochschule Hannover	Hannover		Germany	30625
270	Universitätsklinikum Heidelberg	Heidelberg		Germany	69120
271	SLK-Kliniken Heilbronn GmbH	Heilbronn		Germany	74078
272	Klinikum Idar-Oberstein	Idar-Oberstein		Germany	55743
273	Universitätsklinikum Jena	Jena		Germany	07747
274	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Kiel		Germany	24105
275	Universitätsklinikum Köln (AöR)	Köln		Germany	50937
276	Universitätsklinikum Leipzig	Leipzig		Germany	04103
277	Klinikum der Stadt Ludwigshafen am Rhein gGmbH	Ludwigshafen		Germany	67063
278	Universitätsklinikum Magdeburg AöR	Magdeburg		Germany	39120
279	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz		Germany	55131
280	Universitätsklinikum Gießen und Marburg GmbH	Marburg		Germany	35043
281	Elblandklinikum Meißen	Meißen		Germany	01662
282	Johannes Wesling Klinikum	Minden		Germany	32429
283	Kliniken Maria Hilf GmbH	Moenchengladbach		Germany	41063
284	Ökumenisches Hainich Klinikum gGmbH	Mühlhausen		Germany	99974
285	Klinikum der Universität München - Campus Großhadern	München		Germany	81377
286	Klinikum rechts der Isar der Technischen Universität München	München		Germany	81675
287	Universitätsklinikum Münster	Münster		Germany	48129
288	Klinikum Nürnberg	Nürnberg		Germany	90471
289	Sana Klinikum Offenbach GmbH	Offenbach		Germany	63069
290	Klinikum Osnabrück GmbH	Osnabrück		Germany	49076
291	Universitätsklinikum Regensburg	Regensburg		Germany	93053
292	Nordwest-Krankenhaus Sanderbusch gGmbH	Sande		Germany	26452
293	Kreisklinikum Siegen GmbH	Siegen		Germany	57076
294	Bürgerhospital, Stuttgart	Stuttgart		Germany	70174
295	Nervenklinik Teupitz, Teupitz	Teupitz		Germany	15755
296	Krankenhaus der Barmherzigen Brüder Trier	Trier		Germany	54292
297	Universitätsklinikum Tübingen	Tübingen		Germany	72076
298	RKU - Universitäts- und Rehabilitationskliniken Ulm gGmbH	Ulm		Germany	89081
299	Sophien- und Hufeland-Klinikum gGmbH	Weimar		Germany	99425
300	Helios Dr. Horst Schmidt Kliniken Wiesbaden	Wiesbaden		Germany	65199
301	Universitätsklinikum Würzburg	Würzburg		Germany	97080
302	Univ.Hosp. of Alexandroupolis	Alexandroupolis		Greece	68131
303	Gen.Hosp.of Ath.Evangelismos	Athens		Greece	10676
304	Attikon University Hospital	Athens		Greece	12462
305	Gen.Univ. Hosp. of Herakleion	Herakleion		Greece	71306
306	General University Hospital of Larissa	Larissa		Greece	41110
307	Univ. Gen. Hosp. of Patras	Patras		Greece	26504
308	Univ.Gen.Hosp. of Thessaloniki	Thessaloniki		Greece	54636
309	Prince of Wales Hospital	Hong Kong		Hong Kong	0
310	Pamela Youde Nethersole Eastern Hospital	Hong Kong		Hong Kong
311	Queen Mary Hospital	Hong Kong		Hong Kong
312	Semmelweis University	Budapest		Hungary	1083
313	National Instit.of Neurosciences,Neurology Dept,Budapest	Budapest		Hungary	1145
314	Univ. Debrecen Medical Health Science Center, Neurology Dept	Debrecen		Hungary	4012
315	Pest Megyei Flor Ferenc Hospital	Kistarcsa		Hungary	2143
316	CRU Hungary Ltd, Private Practice, Miskolc	Miskolc		Hungary	3529
317	Univ. of Pecs Clinic for Neurology	Pecs		Hungary	7623
318	St. Johns medical College and Hospital	Bangalore		India	560034
319	Post Graduate Institute of Medical Education and Research	Chandigarh		India	160012
320	Lalitha Super Specialities Hospital	Guntur		India	522001
321	Nizam's Institute of Medical Sciences	Hyderabad		India	500082
322	Shree Krishna Hospital and Research Centre	Karamsad		India	388325
323	Caritas Hospital	Kottayam		India	686016
324	Mangala Hospital and Mangala Kidney Foundation	Mangalore		India	575003
325	LTMMC & GH Medical College,	Mumbai		India	400022
326	Magnum Heart Institute	Nashik		India	422005
327	All India Institute of Medical Sciences	New Delhi		India	110029
328	Sahyadri Speciality Hospital	Pune		India	411004
329	Hillel Yaffe Medical Center, Hadera	Hadera		Israel	38100
330	Wolfson Medical Center	Holon		Israel	58100
331	The Chaim Sheba Medical Center Tel Hashomer	Tel Hashomer, Ramat Gan		Israel	5265601
332	Sourasky Medical Center	Telaviv		Israel	64239
333	Osp. SS Filippo Nicola	Avezzano		Italy	67051
334	Policlinico S. Orsola Malpighi	Bologna		Italy	40138
335	A.O. Spedali Civili di Brescia	Brescia		Italy	25123
336	Azienda Ospedaliero Universitaria di Ferrara	Cona (FE)		Italy	44124
337	Policlinico San Martino	Genova		Italy	16132
338	A.O.U.Policlinico G.Martino	Messina		Italy	98125
339	Fondazione Centro San Raffaele del Monte Tabor	Milano		Italy	20132
340	Istituto Auxologico Italiano	Milano		Italy	20149
341	Nuovo Ospedale Civile S. Agostino-Estense	Modena		Italy	41126
342	Azienda Ospedaliera Universitaria di Padova	Padova		Italy	35128
343	Ospedale S.Maria della Misericordia, AO di Perugia	Perugia		Italy	06156
344	Osp. Guglielmo da Saliceto AUSL di Piacenza	Piacenza		Italy	29121
345	Ospedale Santa Corona Azienda Sanitaria Locale n.2 Savonese	Pietra Ligure		Italy	17027
346	Università degli Studi Campus Bio-Medico	Roma		Italy	00128
347	A.O. San Camillo Forlanini	Roma		Italy	00152
348	Umberto I Pol. di Roma-Università di Roma La Sapienza	Roma		Italy	00161
349	Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza	Roma		Italy	00189
350	A.O.U. Senese Policlinico Santa Maria alle Scotte	Siena		Italy	53100
351	Ospedale Molinette, AO Città della Salute e della	Torino		Italy	10126
352	Ospedale Maria Vittoria	Torino		Italy	10144
353	Ospedale S. Maria di Ca' Foncello Azienda ULSS9 TREVISO	Treviso		Italy	31100
354	A. O. Ospedale Circolo Fond. Macchi	Varese		Italy	21100
355	Ospedale Policlinico G.B. Rossi (Borgo Roma) di Verona	Verona		Italy	37126
356	Chubu Rosai Hospital	Aichi, Nagoya		Japan	455-8530
357	National Hospital Organization Toyohashi Medical Center	Aichi, Toyohashi		Japan	440-8510
358	Toyota Memorial Hospital	Aichi, Toyota		Japan	471-8513
359	Reserch Institute for Brain and Blood Vessels Akita	Akita, Akita		Japan	010-0874
360	Juntendo University Urayasu Hospital	Chiba, Urayasu		Japan	279-0021
361	Go Neurosurgical Clinic	Fukuoka, Chikushi-gun		Japan	811-1244
362	Fukuoka University Chikushi Hospital	Fukuoka, Chikushino		Japan	818-8502
363	National Hospital Organization Kyushu Medical Center	Fukuoka, Fukuoka		Japan	810-8563
364	Fukuoka Wajiro Hospital	Fukuoka, Fukuoka		Japan	811-0213
365	Fukuoka University Hospital	Fukuoka, Fukuoka		Japan	814-0180
366	Fukuoka Tokushukai Medical Center	Fukuoka, Kasuga		Japan	816-0864
367	Steel Memorial Yawata Hospital	Fukuoka, Kitakyushu		Japan	805-0050
368	Japan Community Health Care Organization Kyushu Hospital	Fukuoka, Kitakyushu		Japan	806-8501
369	St. Mary's Hospital	Fukuoka, Kurume		Japan	830-8543
370	Shin Koga Hospital	Fukuoka, Kurume		Japan	830-8577
371	Fukuoka Shin Mizumaki Hospital	Fukuoka, Onga		Japan	807-0051
372	Social Insurance Tagawa Hospital	Fukuoka, Tagawa		Japan	826-8585
373	Shin Yukuhashi Hospital	Fukuoka, Yukuhashi		Japan	824-0026
374	Fujita General Hospital	Fukushima, Date-Gun		Japan	969-1793
375	Shinseikai Masu Memorial Hospital	Fukushima, Nihonmatsu		Japan	964-0867
376	Asahi University Hospital	Gifu, Gifu		Japan	500-8523
377	Japanese Red Cross Takayama Hospital	Gifu, Takayama		Japan	506-8550
378	Mihara Memorial Hospital	Gunma, Isesaki		Japan	372-0006
379	Maebashi Red Cross Hospital	Gunma, Maebashi		Japan	371-0014
380	Medical corporation Suiseikai Suiseikai Kajikawa Hospital	Hiroshima, Hiroshima		Japan	730-0046
381	Araki Neurosurgical Hospital	Hiroshima, Hiroshima		Japan	733-0821
382	Hiroshima Prefectural Hospital	Hiroshima, Hiroshima		Japan	734-8530
383	Sapporo Shiroishi Memorial Hospital	Hokkaido, Sapporo		Japan	003-0026
384	Nakamura Memorial Hospital	Hokkaido, Sapporo		Japan	060-8570
385	Kobe City Medical Center General Hospital	Hyogo, Kobe		Japan	650-0047
386	JA Toride Medical Center	Ibaraki, Toride		Japan	302-0022
387	Tsukuba Medical Center Hospital	Ibaraki, Tsukuba		Japan	305-8558
388	Iwate Medical University Hospital	Iwate, Morioka		Japan	020-8505
389	Kagoshima City Hospital	Kagoshima, Kagoshima		Japan	890-8760
390	National Hospital Organization Kagoshima Medical Center	Kagoshima, Kagoshima		Japan	892-0853
391	Shonan Kamakura General Hospital	Kanagawa, Kamakura		Japan	247-8533
392	Saiseikai Kumamoto Hospital	Kumamoto, Kumamoto		Japan	861-4193
393	Japanese Red Cross Kumamoto Hospital	Kumamoto, Kumamoto		Japan	861-8520
394	Kumamoto City Hospital	Kumamoto, Kumamoto		Japan	862-8505
395	Uji-Tokushukai Medical Center	Kyoto, Uji		Japan	611-0042
396	National Hospital Organization Sendai Medical Center	Miyagi, Sendai		Japan	983-8520
397	South Miyagi Medical Center	Miyagi, Shibata-gun		Japan	989-1253
398	Ina Central Hospital	Nagano, Ina		Japan	396-8555
399	Nagano Municipal Hospital	Nagano, Naganoi		Japan	381-8551
400	Nagasaki University Hospital	Nagasaki, Nagasaki		Japan	852-8501
401	Nozaki Tokushukai Hospital	Osaka, Daito		Japan	574-0074
402	Higashiosaka City Medical Center	Osaka, Higashiosaka		Japan	578-8588
403	Wakakusa Daiichi Hospital	Osaka, Higashiosaka		Japan	579-8056
404	Rinku General Medical Center	Osaka, Izumisano		Japan	598-8577
405	Kishiwada Tokushukai Hospital	Osaka, Kishiwada		Japan	596-0042
406	Yagi Neurosurgical Hospital	Osaka, Osaka		Japan	537-0011
407	Tominaga Hospital	Osaka, Osaka		Japan	556-0017
408	Osaka University Hospital	Osaka, Suita		Japan	565-0871
409	TMG Asaka Medical Center	Saitama, Asaka		Japan	351-0023
410	Saitama Medical University International Medical Center	Saitama, Hidaka		Japan	350-1298
411	Sainokuni Higashiomiya Medical Center	Saitama, Saitama		Japan	331-8577
412	Saitama Municipal Hospital	Saitama, Saitama		Japan	336-8522
413	Nippon Medical School Hospital	Tokyo, Bunkyo-ku		Japan	113-8603
414	Tokyo Metropolitan Geriatric Hospital	Tokyo, Itabashi-ku		Japan	173-0015
415	Kyorin University Hospital	Tokyo, Mitaka		Japan	181-8611
416	Tokyo Women's Medical University Hospital	Tokyo, Shinjuku-ku		Japan	162-8666
417	Saiseikai Wakayama Hospital	Wakayama, Wakayama		Japan	640-8158
418	Yamagata City Hospital SAISEIKAN	Yamagata, Yamagata		Japan	990-8533
419	Hallym University Sacred Heart Hospital	Anyang		Korea, Republic of	431-070
420	Dong-A University Hospital	Busan		Korea, Republic of	602-715
421	Kyungpook National Univ. Hosp	Daegu		Korea, Republic of	700-721
422	Chungnam National University Hospital	Daejoen		Korea, Republic of	35015
423	Inje University Ilsan Paik Hospital	Goyang		Korea, Republic of	411-706
424	Chonnam National University Hospital	Gwangju		Korea, Republic of	501-757
425	Chosun University Hospital	Gwangju		Korea, Republic of	61453
426	Seoul National University Bundang Hospital	Seongnam		Korea, Republic of	463-707
427	Severance Hospital	Seoul		Korea, Republic of	03722
428	Asan Medical Center	Seoul		Korea, Republic of	05505
429	The Catholic University of Korea, Seoul St.Mary's Hospital	Seoul		Korea, Republic of	06591
430	Chung-Ang University Hospital	Seoul		Korea, Republic of	06973
431	Korea University Guro Hospital	Seoul		Korea, Republic of	08308
432	Kangdong Sacred Heart Hospital	Seoul		Korea, Republic of	134-701
433	Samsung Medical Center	Seoul		Korea, Republic of	135-710
434	SMG-SNU Boramae Medical Center	Seoul		Korea, Republic of	156-707
435	Ajou University Hospital	Suwon		Korea, Republic of	443-380
436	Sarawak General Hospital	Kuching		Malaysia	93586
437	Hospital Seberang Jaya	Pulau Pinang		Malaysia	13700
438	Hospital Sultanah Nur Zahirah	Terengganu		Malaysia	20400
439	Hospital General de Culiacán "Dr. Bernardo J. Gastellum"	Culiacán		Mexico	80230
440	Hospital General "Dr. Miguel Silva"	Morelia		Mexico	58000
441	Hospital Angeles del Pedregal	México, D.F.		Mexico	10700
442	Hospital Universitario Dr Jose Eleuterio Gonzalez	Nuevo Leon		Mexico	64460
443	H. Central Dr Ignacio M. P.	San Luis Potosi		Mexico	78250
444	Auckland City Hospital	Grafton / Auckland		New Zealand	1010
445	North Shore Hospital, Takapuna	Takpuna Auckland		New Zealand	0622
446	Wellington Hospital	Wellington		New Zealand	6212
447	Instituto Nacional de Ciencias Neurológicas	Barrios Altos		Peru
448	Hospital Nacional Guillermo Almenara Irigoyen	La Victoria		Peru	Lima-13
449	PI HOUSE Sp. z o.o., Gdansk	Gdansk		Poland	80546
450	Spec.Hosp.of Dr. Wladyslaw Bieganski in Grudziadz	Grudziadz		Poland	86300
451	Univ.Clin.Centr Gibinski of Silesian Med,Neurol.dep,Katowice	Katowice		Poland	40514
452	University Hospital in Krakow	Krakow		Poland	31503
453	Center of Clinical Neurology, private prac, Krakow	Krakow		Poland	31505
454	Clin.Research Center,Leszek Szczepanski,Private Prac.,Lublin	Lublin		Poland	20022
455	Medicome Sp. z o.o.	Oswiecim		Poland	32-600
456	Specialist Holy Spirit Hospital, Neurology Dept,Sandomierz	Sandomierz		Poland	27600
457	Public Central Clinical Hosp,Neurology Clinic,Warsaw	Warsaw		Poland	02097
458	Military Institute of Medicine Neurology Clinic, Warsaw	Warsaw		Poland	04 141
459	Hospital Garcia de Orta, EPE	Almada		Portugal	2801-951
460	Hospital Fernando Fonseca, EPE	Amadora		Portugal	2720-276
461	Hospital de Braga - Centro Clínico Académico (2CA)	Braga		Portugal	4710-243
462	CHUC - Centro Hospitalar e Universitário de Coimbra, EPE	Coimbra		Portugal	3004-561
463	CHLC, EPE - Hospital de São José	Lisboa		Portugal	1150-199
464	CHLO, EPE - Hospital Egas Moniz	Lisboa		Portugal	1349-019
465	CHULN, EPE - Hospital de Santa Maria	Lisboa		Portugal	1649-035
466	Hospital Beatriz Ângelo	Loures		Portugal	2674-514
467	USLM, EPE - Hospital Pedro Hispano	Matosinhos		Portugal	4454-509
468	H. Santo António - Centro Hospitalar do Porto	Porto		Portugal	4099-001
469	Centro Hospitalar São João,EPE	Porto		Portugal	4202-451
470	Centro Hospitalar de Entre o Douro e Vouga, E.P.E. - Hospital de São Sebastião	Santa Maria da Feira		Portugal	4520-211
471	Interreg. Clinical & Diagnostic Center, Neurol. Dept., Kazan	Kazan		Russian Federation	420101
472	Reg.Clin.Hosp#1 na S.V.Ochapovskiy,Neurology#1 Dep,Krasnodar	Krasnodar		Russian Federation	350086
473	City Clin.Emergency Hosp of Kursk, Neurology Department No.2	Kursk		Russian Federation	305035
474	Clin.Hosp#2,na.Semashko,Russ.Railways,Restorative Med&Rehab.	Moscow		Russian Federation	107150
475	CityClin.Hosp na I.V.Davydovsky of Dept of Healthcare Moscow	Moscow		Russian Federation	109240
476	Research&Clini Cent Neuropsychiatry Dep. Healthcare,Moscow	Moscow		Russian Federation	115419
477	City Clin.Hosp#1na N.I.Pirogov,Dept of Healthcare of Moscow	Moscow		Russian Federation	117049
478	Ltd liabilityCom.CityNeurologic Cntr Sibneiromed,Novosibirsk	Novosibirsk		Russian Federation	630091
479	Saratov State Med.Univ na V.I.Razumovsky,FacultyTherapy Clin	Saratov		Russian Federation	410054
480	Reg.State Instit.of Healthc.Smolensk Reg.Clin.Hosp,Neurology	Smolensk		Russian Federation	214018
481	Research Inst. of Emerg. Med., Vascul. Center,St. Petersburg	St. Petersburg		Russian Federation	192242
482	Military Medical Academy n.a. C. M. Kirov, St. Petersburg	St. Petersburg		Russian Federation	194044
483	Sverdlovsk Reg.Clin.Hosp.No.1	Yekaterinburg		Russian Federation	620102
484	Clinical Center of Serbia	Belgrade		Serbia	11000
485	Special Hosp.for Cerebrovascul.Disease,'Sveti Sava,Belgrade	Belgrade		Serbia	11000
486	Clinical Centre Nis	Nis		Serbia	18000
487	Clinical Center of Vojvodina	Novi Sad		Serbia	21000
488	National University Hospital	Singapore		Singapore	119074
489	Singapore General Hospital	Singapore		Singapore	169037
490	National Neuroscience Institute	Singapore		Singapore	308433
491	Faculty Hospital L. Pasteura, Kosice	Kosice		Slovakia	40 66
492	Faculty Hospital Nitra	Nitra		Slovakia	950 01
493	Instit.f.applicative Research in med.rehab.Dobrna	Dobrna		Slovenia	3204
494	Cardial d.o.o., Specialist out-patient unit, Ljubljana	Ljubljana		Slovenia	1000
495	Univ. Medical Center Maribor	Maribor		Slovenia	2000
496	University of Pretoria	Pretoria		South Africa	0002
497	Dr. Moodley and Dr. Sarvan	Tongaat		South Africa	4400
498	Hospital General Universitario de Albacete	Albacete		Spain	02006
499	Hospital del Mar	Barcelona		Spain	08003
500	Hospital Santa Creu i Sant Pau	Barcelona		Spain	08025
501	Hospital Vall d'Hebron	Barcelona		Spain	08035
502	Hospital Universitari de Girona Doctor Josep Trueta	Girona		Spain	17007
503	Hospital Arnau de Vilanova	Lleida		Spain	25198
504	Hospital La Princesa	Madrid		Spain	28006
505	Hospital General Universitario Gregorio Marañón	Madrid		Spain	28007
506	Hospital Ramón y Cajal	Madrid		Spain	28034
507	Hospital Clínico San Carlos	Madrid		Spain	28040
508	Hospital La Paz	Madrid		Spain	28046
509	Hospital Son Espases	Palma de Mallorca		Spain	07010
510	Complejo Hospitalario de Navarra	Pamplona		Spain	31008
511	Hospital Universitario Donostia	San Sebastian		Spain	20014
512	Hospital Clínico de Santiago	Santiago de Compostela		Spain	15706
513	Hospital Virgen del Rocío	Sevilla		Spain	41013
514	Hospital Universitari Joan XXIII	Tarragona		Spain	43005
515	Hospital Mútua Terrassa	Tarrasa (Barcelona)		Spain	08221
516	Hospital Clínico de Valencia	Valencia		Spain	46010
517	Hospital Clínico Universitario de Valladolid	Valladolid		Spain	47005
518	Sahlgrenska US, Göteborg	Göteborg		Sweden	413 45
519	Sahlgrenska Universitetssjukhuset, Östra	Göteborg		Sweden	416 85
520	Skaraborgs Sjukhus	Skövde		Sweden	541 85
521	Karolinska Univ. sjukhuset	Stockholm		Sweden	141 86
522	Karolinska Univ. sjukhuset	Stockholm		Sweden	171 76
523	Danderyds Sjukhus	Stockholm		Sweden	182 88
524	Canton Hospital Aarau, Neurology Dept., Stroke Center	Aarau		Switzerland	5001
525	University Hospital Basel	Basel		Switzerland	4031
526	Univ. Hospital Bern, Neurology Dept, Stroke Center	Bern		Switzerland	3010
527	CHUV - Centre hospitalier universitaire vaudois	Lausanne		Switzerland	1011
528	Regional Hospital Lugano,Neurocenter of Southern Switzerland	Lugano		Switzerland	6903
529	Kantonsspital St.Gallen	St. Gallen		Switzerland	9007
530	University Hosp. Zürich, Dept. of Neurology, Stroke Center	Zürich		Switzerland	8901
531	Chang-Hua Christian Hospital	Changhua		Taiwan	500
532	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan	83301
533	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan	8807
534	China Medical University Hospital	Taichung		Taiwan	404
535	Taichung Veterans General Hospital	Taichung		Taiwan	40750
536	Chi Mei Medical Center	Tainan,		Taiwan	71004
537	NCKUH	Tainan		Taiwan	704
538	National Taiwan University Hospital	Taipei		Taiwan	100
539	Mackay Memorial Hospital	Taipei		Taiwan	10449
540	Cheng Hsin General Hospital	Taipei		Taiwan	112
541	Taipe Veterans General Hospital	Taipei		Taiwan	112
542	Tri-Service General Hospital	Taipei		Taiwan	11490
543	Chang Gung Memorial Hospital(TaoYuan)	Taoyuan		Taiwan	330
544	Chulalongkorn University	Bangkok		Thailand	10330
545	Ramathibodi Hospital	Bangkok		Thailand	10400
546	Siriraj Hospital	Bangkok		Thailand	10700
547	Lampang Hospital	Lampang		Thailand	52000
548	Ankara Universitesi Tip Fakultesi	Ankara		Turkey	06100
549	Hacettepe Universitesi Tip Fakultesi Noroloji A.B.D.	Ankara		Turkey	06100
550	Gazi Universitesi Tip Fakultesi	Ankara		Turkey	06500
551	Eskisehir Osmangazi Universitesi Tip Fakultesi	Eskisehir		Turkey	26480
552	Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi	Istanbul		Turkey	34093
553	Istanbul Universitesi Istanbul Tip Fakultesi Noroloji A.B.D.	Istanbul		Turkey	34093
554	Istanbul Universitesi Cerrahpasa Tip Fakultesi	Istanbul		Turkey	34098
555	Bakırkoy Dr. Sadi Konuk Egitim Ve Arastirma Hastanesi	Istanbul		Turkey	34147
556	Bakirkoy Prof. Dr. Mazhar Osman Ruh Sagligi ve Sinir Hastaliklari	Istanbul		Turkey	34147
557	Sisli Hamidiye Etfal Egitim ve Arastirma Hastanesi	Istanbul		Turkey	34371
558	Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi	Istanbul		Turkey	34890
559	Dokuz Eylul Universitesi Tip Fakultesi Noroloji A.B.D.	Izmir		Turkey	35340
560	Ondokuz Mayis Universitesi Tip Fakultesi	Samsun		Turkey	55139
561	Namik Kemal Universitesi Tip Fakultesi	Tekirdag		Turkey	59100
562	Bukovinian Med.Univ.Chernivtsi Reg.Psychiatric Hosp,Neurolog	Chernivtsi		Ukraine	58018
563	City Clinical Hospital No. 7, Kharkov	Kharkiv		Ukraine	76000
564	Instit.of Neurol,Psychiatry&Narcol,Vascul. Malformations Dep	Kharkiv		Ukraine	76000
565	Instit.of Gerontology na D.F.Chebotarev,Brain Vascular Path.	Kyiv		Ukraine	4114
566	Lviv Regional Clinical Hospital, Lviv	Lviv		Ukraine	79010
567	Ternopil State Med.Univ.na Gorbachevskiy,Neurology Dept N3	Ternopil		Ukraine	46027
568	Vinnitsia Reg.Psychoneurol.Hosp.na Yushchenko,Dept.N3,Neurol	Vinnitsia		Ukraine	21005
569	Zhytomyr Reg.ClinHosp na Gerbachevskiy RegCouncil,Neurol.Dep	Zhytomyr		Ukraine	10002

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

More Information

Additional Information:

Related Info

Publications

None provided.

Responsible Party:

Boehringer Ingelheim

ClinicalTrials.gov Identifier:

NCT02239120

Other Study ID Numbers:

1160.189
2013-003444-24

First Posted:

Sep 12, 2014

Last Update Posted:

Sep 6, 2019

Last Verified:

Aug 1, 2019

Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details	This was randomised, active comparator, double-blind, 2 arms (1:1 ratio) event-driven Phase III trial in participants with embolic stroke of undetermined source (ESUS). Study was conducted at multiple centers in 42 countries between 3 Dec 2014 (first participant enrollment) and 14 August 2018 (last participant visit).
Pre-assignment Detail	All participants were screened for eligibility to participate in the trial. Participants attended specialist sites which would then ensured that all participants met all inclusion/exclusion criteria. Participants were not to be randomized to trial treatment if any one of the specific entry criteria were not met.

Arm/Group Title	Dabigatran Etexilate 110 or 150 Milligram (mg)	Acetylsalicylic Acid, Aspirin (ASA) 100 mg
Arm/Group Description	Participants were orally administered one 110 mg (for participants aged ≥75 years or with a creatinine clearance (CrCl) of 30 to <50 millilitre/ minute (mL/min)) or one 150 mg (for participants aged <75 years and with a CrCl of ≥50 mL/minute) Dabigatran etexilate (DE) capsule twice daily.	Participants were orally administered one 100 mg Aspirin non-enteric coated tablet once daily.
Period Title: Overall Study
STARTED	2695	2695
COMPLETED	2620	2623
NOT COMPLETED	75	72

Baseline Characteristics

Arm/Group Title	Dabigatran Etexilate 110 or 150 Milligram (mg)	Acetylsalicylic Acid, Aspirin (ASA) 100 mg	Total
Arm/Group Description	Participants were orally administered one 110 mg (for participants aged ≥75 years or with a creatinine clearance (CrCl) of 30 to <50 millilitre/ minute (mL/min)) or one 150 mg (for participants aged <75 years and with a CrCl of ≥50 mL/minute) Dabigatran etexilate (DE) capsule twice daily.	Participants were orally administered one 100 mg Aspirin non-enteric coated tablet once daily.	Total of all reporting groups
Overall Participants	2695	2695	5390
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.5 (11.44)	63.9 (11.39)	64.2 (11.42)
Sex: Female, Male (Count of Participants)
Female	1001 37.1%	986 36.6%	1987 36.9%
Male	1694 62.9%	1709 63.4%	3403 63.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	281 10.4%	268 9.9%	549 10.2%
Not Hispanic or Latino	2354 87.3%	2371 88%	4725 87.7%
Unknown or Not Reported	60 2.2%	56 2.1%	116 2.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	11 0.4%	20 0.7%	31 0.6%
Asian	631 23.4%	597 22.2%	1228 22.8%
Native Hawaiian or Other Pacific Islander	2 0.1%	4 0.1%	6 0.1%
Black or African American	54 2%	40 1.5%	94 1.7%
White	1926 71.5%	1966 72.9%	3892 72.2%
More than one race	10 0.4%	12 0.4%	22 0.4%
Unknown or Not Reported	61 2.3%	56 2.1%	117 2.2%

Outcome Measures

1. Primary Outcome

Title	Adjudicated Recurrent Stroke
Description	Adjudicated recurrent stroke (ischemic, hemorrhagic, or unspecified) is presented. The annualised event rate represents the average number of events per patient during a 1-year period.
Time Frame	From randomisation until full follow up period, approximately 43 months.

Outcome Measure Data

Analysis Population Description
Randomised set (RS): RS consisted of all participants who were randomised, regardless of whether they took trial medication. The start date of the observation period for this population was the date of randomisation.

Arm/Group Title	Dabigatran Etexilate 110 or 150 Milligram (mg)	Acetylsalicylic Acid, Aspirin (ASA) 100 mg
Arm/Group Description	Participants were orally administered one 110 mg (for participants aged ≥75 years or with a creatinine clearance (CrCl) of 30 to <50 millilitre/ minute (mL/min)) or one 150 mg (for participants aged <75 years and with a CrCl of ≥50 mL/minute) Dabigatran etexilate (DE) capsule twice daily.	Participants were orally administered one 100 mg Aspirin non-enteric coated tablet once daily.
Measure Participants	2695	2695
Number [Annualised event rate (%/ year)]	4.09	4.80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dabigatran Etexilate 110 or 150 Milligram (mg), Acetylsalicylic Acid, Aspirin (ASA) 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1028
	Comments
	Method	Regression, Cox
	Comments	Covariates in model are age(<or>= 75years), creatinine clearance < or >= 50mL/min and stroke or transient ischaemic attack(TIA) prior to index stroke.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95% 0.69 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	First Major Bleed (Adjudicated)
Description	First major bleed is primary safety endpoint. Major bleeds were defined according to the International Society of Thrombosis and Haemostasis (ISTH) definition as follows: Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome and/or, Bleeding (which should be overt) associated with a reduction in haemoglobin of at least 2 grams/ decilitre (g/dL) (1.24 millimoles Per Litre (mmol/L)), or leading to transfusion of ≥2 units of blood or packed cells (equivalent to ≥4.5 units in Japan); the haemoglobin drop should be considered to be due to and temporally related to the bleeding event and/or, Fatal bleed. The annualised event rate represents the average number of events per patient during a 1-year period.
Time Frame	Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.

Outcome Measure Data

Analysis Population Description
Treated set (TS): TS consisted of all patients who were treated with at least 1 dose of trial medication. The start date of the observation period for this population was the date of first intake of trial medication.

Arm/Group Title	Dabigatran Etexilate 110 or 150 Milligram (mg)	Acetylsalicylic Acid, Aspirin (ASA) 100 mg
Arm/Group Description	Participants were orally administered one 110 mg (for participants aged ≥75 years or with a creatinine clearance (CrCl) of 30 to <50 millilitre/ minute (mL/min)) or one 150 mg (for participants aged <75 years and with a CrCl of ≥50 mL/minute) Dabigatran etexilate (DE) capsule twice daily.	Participants were orally administered one 100 mg Aspirin non-enteric coated tablet once daily.
Measure Participants	2676	2674
Number [Annualised event rate (%/ year)]	1.84	1.33

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dabigatran Etexilate 110 or 150 Milligram (mg), Acetylsalicylic Acid, Aspirin (ASA) 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1076
	Comments
	Method	Regression, Cox
	Comments	Covariates in model are age(<or>= 75years), creatinine clearance < or >= 50mL/min and stroke or transient ischaemic attack(TIA) prior to index stroke.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95% 0.94 to 1.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Adjudicated Ischaemic Stroke
Description	Adjudicated ischaemic stroke is a key secondary endpoint. The annualised event rate represents the average number of events per patient during a 1-year period.
Time Frame	From randomisation until full follow up period, up to 43 months

Outcome Measure Data

Analysis Population Description
RS

Arm/Group Title	Dabigatran Etexilate 110 or 150 Milligram (mg)	Acetylsalicylic Acid, Aspirin (ASA) 100 mg
Arm/Group Description	Participants were orally administered one 110 mg (for participants aged ≥75 years or with a creatinine clearance (CrCl) of 30 to <50 millilitre/ minute (mL/min)) or one 150 mg (for participants aged <75 years and with a CrCl of ≥50 mL/minute) Dabigatran etexilate (DE) capsule twice daily.	Participants were orally administered one 100 mg Aspirin non-enteric coated tablet once daily.
Measure Participants	2695	2695
Number [Annualised event rate (%/ year)]	3.97	4.71

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dabigatran Etexilate 110 or 150 Milligram (mg), Acetylsalicylic Acid, Aspirin (ASA) 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0892
	Comments
	Method	Regression, Cox
	Comments	Covariates in model are age(<or>= 75years), creatinine clearance < or >= 50mL/min and stroke or transient ischaemic attack(TIA) prior to index stroke.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95% 0.68 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Adjudicated Composite of Non-fatal Stroke, Non-fatal Myocardial Infarction, or Cardiovascular Death
Description	Adjudicated composite of non-fatal stroke, non-fatal myocardial infarction (MI), or cardiovascular death is a key secondary endpoint. The annualised event rate represents the average number of events per patient during a 1-year period.
Time Frame	From randomisation until full follow up period, up to 43 months

Outcome Measure Data

Analysis Population Description
RS

Arm/Group Title	Dabigatran Etexilate 110 or 150 Milligram (mg)	Acetylsalicylic Acid, Aspirin (ASA) 100 mg
Arm/Group Description	Participants were orally administered one 110 mg (for participants aged ≥75 years or with a creatinine clearance (CrCl) of 30 to <50 millilitre/ minute (mL/min)) or one 150 mg (for participants aged <75 years and with a CrCl of ≥50 mL/minute) Dabigatran etexilate (DE) capsule twice daily.	Participants were orally administered one 100 mg Aspirin non-enteric coated tablet once daily.
Measure Participants	2695	2695
Number [Annualised event rate (%/ year)]	4.80	5.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dabigatran Etexilate 110 or 150 Milligram (mg), Acetylsalicylic Acid, Aspirin (ASA) 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1911
	Comments
	Method	Regression, Cox
	Comments	Covariates in model are age(<or>= 75years), creatinine clearance < or >= 50mL/min and stroke or transient ischaemic attack(TIA) prior to index stroke.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95% 0.73 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Disabling Stroke
Description	Disabling stroke (modified Rankin Scale greater than or equal to 4, as determined 3 months after recurrent stroke) is presented. The annualised event rate represents the average number of events per patient during a 1-year period.
Time Frame	From randomisation until full follow up period, up to 43 months

Outcome Measure Data

Analysis Population Description
RS

Arm/Group Title	Dabigatran Etexilate 110 or 150 Milligram (mg)	Acetylsalicylic Acid, Aspirin (ASA) 100 mg
Arm/Group Description	Participants were orally administered one 110 mg (for participants aged ≥75 years or with a creatinine clearance (CrCl) of 30 to <50 millilitre/ minute (mL/min)) or one 150 mg (for participants aged <75 years and with a CrCl of ≥50 mL/minute) Dabigatran etexilate (DE) capsule twice daily.	Participants were orally administered one 100 mg Aspirin non-enteric coated tablet once daily.
Measure Participants	2695	2695
Number [Annualised event rate (%/ year)]	0.55	0.93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dabigatran Etexilate 110 or 150 Milligram (mg), Acetylsalicylic Acid, Aspirin (ASA) 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0354
	Comments
	Method	Regression, Cox
	Comments	Covariates in model are age(<or>= 75years), creatinine clearance < or >= 50mL/min and stroke or transient ischaemic attack(TIA) prior to index stroke.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95% 0.36 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	All-cause Death
Description	All-cause death is presented. The annualised event rate represents the average number of events per patient during a 1-year period.
Time Frame	From randomisation until full follow up period, up to 43 months

Outcome Measure Data

Analysis Population Description
RS

Arm/Group Title	Dabigatran Etexilate 110 or 150 Milligram (mg)	Acetylsalicylic Acid, Aspirin (ASA) 100 mg
Arm/Group Description	Participants were orally administered one 110 mg (for participants aged ≥75 years or with a creatinine clearance (CrCl) of 30 to <50 millilitre/ minute (mL/min)) or one 150 mg (for participants aged <75 years and with a CrCl of ≥50 mL/minute) Dabigatran etexilate (DE) capsule twice daily.	Participants were orally administered one 100 mg Aspirin non-enteric coated tablet once daily.
Measure Participants	2695	2695
Number [Annualised event rate (%/ year)]	1.24	1.28

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dabigatran Etexilate 110 or 150 Milligram (mg), Acetylsalicylic Acid, Aspirin (ASA) 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8074
	Comments
	Method	Regression, Cox
	Comments	Covariates in model are age(<or>= 75years), creatinine clearance < or >= 50mL/min and stroke or transient ischaemic attack(TIA) prior to index stroke.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95% 0.66 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Adjudicated Intracranial Hemorrhage
Description	Adjudicated intracranial haemorrhage comprised the subtypes of intracerebral bleeds, intraventricular bleeds, subdural bleeds, epidural bleeds, and subarachnoid bleeds. Microbleeds did not qualify as intracranial haemorrhage, except when they were symptomatic. The annualised event rate represents the average number of events per patient during a 1-year period.
Time Frame	Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.

Outcome Measure Data

Analysis Population Description
TS

Arm/Group Title	Dabigatran Etexilate 110 or 150 Milligram (mg)	Acetylsalicylic Acid, Aspirin (ASA) 100 mg
Arm/Group Description	Participants were orally administered one 110 mg (for participants aged ≥75 years or with a creatinine clearance (CrCl) of 30 to <50 millilitre/ minute (mL/min)) or one 150 mg (for participants aged <75 years and with a CrCl of ≥50 mL/minute) Dabigatran etexilate (DE) capsule twice daily.	Participants were orally administered one 100 mg Aspirin non-enteric coated tablet once daily.
Measure Participants	2676	2674
Number [Annualised event rate (%/ year)]	0.67	0.63

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dabigatran Etexilate 110 or 150 Milligram (mg), Acetylsalicylic Acid, Aspirin (ASA) 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.9064
	Comments
	Method	Regression, Cox
	Comments	Covariates in model are age(<or>= 75years), creatinine clearance < or >= 50mL/min and stroke or transient ischaemic attack(TIA) prior to index stroke.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95% 0.58 to 1.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Adjudicated Fatal Bleed
Description	Adjudicated fatal bleeding was defined as a bleeding event which the Independent Event Adjudication Committee (IAC) determined as the primary cause of death or contributed directly to death. The annualised event rate represents the average number of events per patient during a 1-year period. Because there were 0 events in one treatment group, the hazard ratio is unable to be calculated.
Time Frame	Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.

Outcome Measure Data

Analysis Population Description
TS

Arm/Group Title	Dabigatran Etexilate 110 or 150 Milligram (mg)	Acetylsalicylic Acid, Aspirin (ASA) 100 mg
Arm/Group Description	Participants were orally administered one 110 mg (for participants aged ≥75 years or with a creatinine clearance (CrCl) of 30 to <50 millilitre/ minute (mL/min)) or one 150 mg (for participants aged <75 years and with a CrCl of ≥50 mL/minute) Dabigatran etexilate (DE) capsule twice daily.	Participants were orally administered one 100 mg Aspirin non-enteric coated tablet once daily.
Measure Participants	2676	2674
Number [Annualised event rate (%/ year)]	0.00	0.05

9. Secondary Outcome

Title	Adjudicated Life-threatening Bleed
Description	Major bleeds were to be classified as life-threatening if they met one or more of the following criteria: fatal bleed, symptomatic intracranial bleed, reduction in haemoglobin of at least 5 grams/ deciliter (g/dL), transfusion of at least 4 units of packed red blood cells (equivalent to 9 units in Japan), associated with hypotension requiring the use of intravenous inotropic agents, or necessitated surgical intervention. The annualised event rate represents the average number of events per patient during a 1-year period.
Time Frame	Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.

Outcome Measure Data

Analysis Population Description
TS

Arm/Group Title	Dabigatran Etexilate 110 or 150 Milligram (mg)	Acetylsalicylic Acid, Aspirin (ASA) 100 mg
Arm/Group Description	Participants were orally administered one 110 mg (for participants aged ≥75 years or with a creatinine clearance (CrCl) of 30 to <50 millilitre/ minute (mL/min)) or one 150 mg (for participants aged <75 years and with a CrCl of ≥50 mL/minute) Dabigatran etexilate (DE) capsule twice daily.	Participants were orally administered one 100 mg Aspirin non-enteric coated tablet once daily.
Measure Participants	2676	2674
Number [Annualised event rate (%/ year)]	0.76	0.91

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dabigatran Etexilate 110 or 150 Milligram (mg), Acetylsalicylic Acid, Aspirin (ASA) 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4352
	Comments
	Method	Regression, Cox
	Comments	Covariates in model are age(<or>= 75years), creatinine clearance < or >= 50mL/min and stroke or transient ischaemic attack(TIA) prior to index stroke.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95% 0.49 to 1.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Any Bleed (Investigator-reported)
Description	This was the sum of all major and minor bleeds (Minor bleeds were clinical bleeds that did not fulfil the criteria for major bleeds), regardless of severity. The annualised event rate represents the average number of events per patient during a 1-year period.
Time Frame	Between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months.

Outcome Measure Data

Analysis Population Description
TS

Arm/Group Title	Dabigatran Etexilate 110 or 150 Milligram (mg)	Acetylsalicylic Acid, Aspirin (ASA) 100 mg
Arm/Group Description	Participants were orally administered one 110 mg (for participants aged ≥75 years or with a creatinine clearance (CrCl) of 30 to <50 millilitre/ minute (mL/min)) or one 150 mg (for participants aged <75 years and with a CrCl of ≥50 mL/minute) Dabigatran etexilate (DE) capsule twice daily.	Participants were orally administered one 100 mg Aspirin non-enteric coated tablet once daily.
Measure Participants	2676	2674
Number [Annualised event rate (%/ year)]	15.21	11.64

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dabigatran Etexilate 110 or 150 Milligram (mg), Acetylsalicylic Acid, Aspirin (ASA) 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Regression, Cox
	Comments	Covariates in model are age(<or>= 75years), creatinine clearance < or >= 50mL/min and stroke or transient ischaemic attack(TIA) prior to index stroke.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.28
	Confidence Interval	(2-Sided) 95% 1.12 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

	Dabigatran Etexilate 110 or 150 Milligram (mg)		Acetylsalicylic Acid, Aspirin (ASA) 100 mg
Time Frame	Adverse Events (AE) and serious AE starting between the first trial medication intake up to 6 days after the last trial medication intake, approximately 42 months. All-cause mortality reported from randomisation until full follow up period, approximately 43 months.
Adverse Event Reporting Description	All-cause mortality numbers are based on randomized set whereas Serious Adverse Events (SAE) and non-SAE are based on treated set.

Arm/Group Title	Dabigatran Etexilate 110 or 150 Milligram (mg)		Acetylsalicylic Acid, Aspirin (ASA) 100 mg
Arm/Group Description	Participants were orally administered one 110 mg (for participants aged ≥75 years or with a creatinine clearance (CrCl) of 30 to <50 millilitre/ minute (mL/min)) or one 150 mg (for participants aged <75 years and with a CrCl of ≥50 mL/minute) Dabigatran etexilate (DE) capsule twice daily.		Participants were orally administered one 100 mg Aspirin non-enteric coated tablet once daily.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/2695 (2.1%)		58/2695 (2.2%)
Serious Adverse Events
	Dabigatran Etexilate 110 or 150 Milligram (mg)		Acetylsalicylic Acid, Aspirin (ASA) 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	724/2676 (27.1%)		740/2674 (27.7%)
Blood and lymphatic system disorders
Anaemia	7/2676 (0.3%)		3/2674 (0.1%)
Pancytopenia	1/2676 (0%)		0/2674 (0%)
Disseminated intravascular coagulation	0/2676 (0%)		1/2674 (0%)
Febrile neutropenia	0/2676 (0%)		1/2674 (0%)
Hypochromic anaemia	0/2676 (0%)		1/2674 (0%)
Iron deficiency anaemia	2/2676 (0.1%)		0/2674 (0%)
Cardiac disorders
Acute myocardial infarction	11/2676 (0.4%)		8/2674 (0.3%)
Angina pectoris	3/2676 (0.1%)		4/2674 (0.1%)
Angina unstable	4/2676 (0.1%)		2/2674 (0.1%)
Aortic valve incompetence	1/2676 (0%)		0/2674 (0%)
Atrial fibrillation	24/2676 (0.9%)		20/2674 (0.7%)
Atrial fibrillation or atrial flutter	34/2676 (1.3%)		29/2674 (1.1%)
Atrial flutter	10/2676 (0.4%)		10/2674 (0.4%)
Cardiac disorder	1/2676 (0%)		0/2674 (0%)
Cardiac failure	5/2676 (0.2%)		10/2674 (0.4%)
Cardiac failure acute	1/2676 (0%)		2/2674 (0.1%)
Cardiac failure congestive	4/2676 (0.1%)		2/2674 (0.1%)
Congestive cardiomyopathy	0/2676 (0%)		1/2674 (0%)
Coronary artery disease	6/2676 (0.2%)		11/2674 (0.4%)
Coronary artery stenosis	0/2676 (0%)		3/2674 (0.1%)
Myocardial infarction	8/2676 (0.3%)		8/2674 (0.3%)
Prinzmetal angina	2/2676 (0.1%)		1/2674 (0%)
Sinus node dysfunction	1/2676 (0%)		1/2674 (0%)
Ventricular extrasystoles	0/2676 (0%)		1/2674 (0%)
Acute coronary syndrome	1/2676 (0%)		1/2674 (0%)
Arrhythmia	1/2676 (0%)		2/2674 (0.1%)
Atrial tachycardia	1/2676 (0%)		0/2674 (0%)
Atrioventricular block second degree	2/2676 (0.1%)		1/2674 (0%)
Bradycardia	2/2676 (0.1%)		0/2674 (0%)
Cardiac arrest	3/2676 (0.1%)		5/2674 (0.2%)
Cardiac failure chronic	1/2676 (0%)		0/2674 (0%)
Cardiac ventricular thrombosis	0/2676 (0%)		1/2674 (0%)
Cardio-respiratory arrest	0/2676 (0%)		1/2674 (0%)
Cardiomyopathy	0/2676 (0%)		1/2674 (0%)
Myocardial ischaemia	1/2676 (0%)		0/2674 (0%)
Myocarditis	2/2676 (0.1%)		0/2674 (0%)
Palpitations	2/2676 (0.1%)		0/2674 (0%)
Right ventricular failure	0/2676 (0%)		1/2674 (0%)
Sinoatrial block	1/2676 (0%)		0/2674 (0%)
Sinus arrest	0/2676 (0%)		1/2674 (0%)
Sinus bradycardia	1/2676 (0%)		0/2674 (0%)
Ventricular tachycardia	1/2676 (0%)		3/2674 (0.1%)
Congenital, familial and genetic disorders
Heart disease congenital	0/2676 (0%)		1/2674 (0%)
Atrial septal defect	3/2676 (0.1%)		4/2674 (0.1%)
Corneal dystrophy	0/2676 (0%)		1/2674 (0%)
Cryopyrin associated periodic syndrome	1/2676 (0%)		0/2674 (0%)
Factor V Leiden mutation	0/2676 (0%)		1/2674 (0%)
Phimosis	4/2676 (0.1%)		1/2674 (0%)
Ventricular septal defect	1/2676 (0%)		0/2674 (0%)
Ear and labyrinth disorders
Deafness	2/2676 (0.1%)		1/2674 (0%)
Deafness neurosensory	2/2676 (0.1%)		0/2674 (0%)
Sudden hearing loss	6/2676 (0.2%)		1/2674 (0%)
Vertigo	7/2676 (0.3%)		8/2674 (0.3%)
Vertigo positional	3/2676 (0.1%)		3/2674 (0.1%)
Endocrine disorders
Inappropriate antidiuretic hormone secretion	1/2676 (0%)		0/2674 (0%)
Adrenal haematoma	1/2676 (0%)		0/2674 (0%)
Adrenal mass	0/2676 (0%)		1/2674 (0%)
Goitre	1/2676 (0%)		0/2674 (0%)
Hyperthyroidism	0/2676 (0%)		1/2674 (0%)
Hypothyroidism	1/2676 (0%)		0/2674 (0%)
Toxic nodular goitre	1/2676 (0%)		0/2674 (0%)
Eye disorders
Cataract	4/2676 (0.1%)		7/2674 (0.3%)
Diabetic retinopathy	1/2676 (0%)		0/2674 (0%)
Eye haemorrhage	1/2676 (0%)		0/2674 (0%)
Glaucoma	6/2676 (0.2%)		6/2674 (0.2%)
Macular degeneration	3/2676 (0.1%)		2/2674 (0.1%)
Macular fibrosis	1/2676 (0%)		2/2674 (0.1%)
Pterygium	0/2676 (0%)		1/2674 (0%)
Retinal drusen	0/2676 (0%)		1/2674 (0%)
Vitreous haemorrhage	1/2676 (0%)		0/2674 (0%)
Age-related macular degeneration	1/2676 (0%)		0/2674 (0%)
Amaurosis	0/2676 (0%)		1/2674 (0%)
Amaurosis fugax	3/2676 (0.1%)		1/2674 (0%)
Angle closure glaucoma	0/2676 (0%)		1/2674 (0%)
Blepharitis	1/2676 (0%)		0/2674 (0%)
Cataract nuclear	1/2676 (0%)		0/2674 (0%)
Dacryostenosis acquired	1/2676 (0%)		0/2674 (0%)
Idiopathic orbital inflammation	1/2676 (0%)		0/2674 (0%)
Macular hole	0/2676 (0%)		1/2674 (0%)
Narrow anterior chamber angle	0/2676 (0%)		1/2674 (0%)
Optic atrophy	0/2676 (0%)		1/2674 (0%)
Optic ischaemic neuropathy	0/2676 (0%)		1/2674 (0%)
Retinal artery occlusion	2/2676 (0.1%)		0/2674 (0%)
Retinal detachment	0/2676 (0%)		1/2674 (0%)
Retinal tear	1/2676 (0%)		0/2674 (0%)
Vision blurred	1/2676 (0%)		0/2674 (0%)
Visual impairment	2/2676 (0.1%)		1/2674 (0%)
Gastrointestinal disorders
Abdominal pain	3/2676 (0.1%)		1/2674 (0%)
Colitis	0/2676 (0%)		2/2674 (0.1%)
Duodenal ulcer haemorrhage	1/2676 (0%)		0/2674 (0%)
Enterocolitis	0/2676 (0%)		1/2674 (0%)
Gastric ulcer	2/2676 (0.1%)		1/2674 (0%)
Gastric ulcer haemorrhage	2/2676 (0.1%)		1/2674 (0%)
Haematochezia	1/2676 (0%)		0/2674 (0%)
Haemorrhoids	0/2676 (0%)		1/2674 (0%)
Hiatus hernia	0/2676 (0%)		2/2674 (0.1%)
Inguinal hernia	5/2676 (0.2%)		3/2674 (0.1%)
Intra-abdominal haemorrhage	0/2676 (0%)		1/2674 (0%)
Ischaemic enteritis	0/2676 (0%)		1/2674 (0%)
Large intestine polyp	2/2676 (0.1%)		1/2674 (0%)
Melaena	0/2676 (0%)		1/2674 (0%)
Rectal perforation	0/2676 (0%)		1/2674 (0%)
Upper gastrointestinal haemorrhage	1/2676 (0%)		3/2674 (0.1%)
Abdominal discomfort	0/2676 (0%)		1/2674 (0%)
Abdominal hernia	1/2676 (0%)		0/2674 (0%)
Abdominal pain upper	1/2676 (0%)		0/2674 (0%)
Anal fissure	1/2676 (0%)		0/2674 (0%)
Anal fistula	1/2676 (0%)		0/2674 (0%)
Appendix disorder	0/2676 (0%)		1/2674 (0%)
Colitis ischaemic	1/2676 (0%)		0/2674 (0%)
Colitis ulcerative	1/2676 (0%)		0/2674 (0%)
Constipation	2/2676 (0.1%)		2/2674 (0.1%)
Diarrhoea	1/2676 (0%)		1/2674 (0%)
Duodenal ulcer	0/2676 (0%)		1/2674 (0%)
Erosive oesophagitis	1/2676 (0%)		0/2674 (0%)
Faecaloma	1/2676 (0%)		0/2674 (0%)
Gastric haemorrhage	2/2676 (0.1%)		1/2674 (0%)
Gastric polyps	1/2676 (0%)		0/2674 (0%)
Gastritis	1/2676 (0%)		0/2674 (0%)
Gastrointestinal haemorrhage	7/2676 (0.3%)		5/2674 (0.2%)
Gastrointestinal necrosis	0/2676 (0%)		1/2674 (0%)
Gastrointestinal ulcer haemorrhage	0/2676 (0%)		1/2674 (0%)
Gastrooesophageal reflux disease	0/2676 (0%)		1/2674 (0%)
Haemorrhoidal haemorrhage	0/2676 (0%)		1/2674 (0%)
Ileal perforation	0/2676 (0%)		1/2674 (0%)
Ileus	1/2676 (0%)		1/2674 (0%)
Intestinal ischaemia	0/2676 (0%)		1/2674 (0%)
Intestinal obstruction	0/2676 (0%)		3/2674 (0.1%)
Intestinal perforation	1/2676 (0%)		0/2674 (0%)
Intestinal polyp	1/2676 (0%)		0/2674 (0%)
Irritable bowel syndrome	1/2676 (0%)		0/2674 (0%)
Large intestine perforation	1/2676 (0%)		0/2674 (0%)
Lower gastrointestinal haemorrhage	1/2676 (0%)		1/2674 (0%)
Nausea	3/2676 (0.1%)		2/2674 (0.1%)
Pancreatitis acute	1/2676 (0%)		0/2674 (0%)
Pancreatitis chronic	1/2676 (0%)		1/2674 (0%)
Peritoneal haemorrhage	1/2676 (0%)		0/2674 (0%)
Rectal haemorrhage	2/2676 (0.1%)		1/2674 (0%)
Retroperitoneal haemorrhage	0/2676 (0%)		1/2674 (0%)
Small intestinal obstruction	0/2676 (0%)		2/2674 (0.1%)
Subileus	0/2676 (0%)		1/2674 (0%)
Vomiting	1/2676 (0%)		1/2674 (0%)
General disorders
Asthenia	2/2676 (0.1%)		1/2674 (0%)
Chest pain	7/2676 (0.3%)		5/2674 (0.2%)
Pyrexia	2/2676 (0.1%)		2/2674 (0.1%)
Chest discomfort	1/2676 (0%)		0/2674 (0%)
Death	3/2676 (0.1%)		6/2674 (0.2%)
Fatigue	1/2676 (0%)		1/2674 (0%)
Feeling cold	0/2676 (0%)		1/2674 (0%)
Gait disturbance	0/2676 (0%)		2/2674 (0.1%)
General physical health deterioration	1/2676 (0%)		0/2674 (0%)
Ill-defined disorder	1/2676 (0%)		0/2674 (0%)
Incarcerated hernia	1/2676 (0%)		0/2674 (0%)
Inflammation	1/2676 (0%)		0/2674 (0%)
Malaise	0/2676 (0%)		3/2674 (0.1%)
Necrosis	0/2676 (0%)		1/2674 (0%)
Oedema peripheral	2/2676 (0.1%)		0/2674 (0%)
Sudden cardiac death	0/2676 (0%)		1/2674 (0%)
Sudden death	0/2676 (0%)		1/2674 (0%)
Vascular stent stenosis	0/2676 (0%)		1/2674 (0%)
Hepatobiliary disorders
Bile duct stone	0/2676 (0%)		3/2674 (0.1%)
Cholecystitis	1/2676 (0%)		1/2674 (0%)
Cholecystitis acute	3/2676 (0.1%)		1/2674 (0%)
Cholelithiasis	4/2676 (0.1%)		3/2674 (0.1%)
Hepatic function abnormal	0/2676 (0%)		1/2674 (0%)
Hepatitis acute	1/2676 (0%)		0/2674 (0%)
Hyperbilirubinaemia	1/2676 (0%)		0/2674 (0%)
Acute hepatic failure	1/2676 (0%)		0/2674 (0%)
Bile duct obstruction	0/2676 (0%)		1/2674 (0%)
Cholecystitis chronic	1/2676 (0%)		0/2674 (0%)
Hepatic failure	1/2676 (0%)		0/2674 (0%)
Jaundice	0/2676 (0%)		1/2674 (0%)
Jaundice cholestatic	0/2676 (0%)		1/2674 (0%)
Immune system disorders
Anaphylactic reaction	1/2676 (0%)		0/2674 (0%)
Hypersensitivity	1/2676 (0%)		0/2674 (0%)
Infections and infestations
Appendicitis	2/2676 (0.1%)		2/2674 (0.1%)
Bronchitis	2/2676 (0.1%)		1/2674 (0%)
Bronchitis bacterial	0/2676 (0%)		1/2674 (0%)
Cellulitis	3/2676 (0.1%)		1/2674 (0%)
Erysipelas	2/2676 (0.1%)		0/2674 (0%)
Escherichia sepsis	1/2676 (0%)		0/2674 (0%)
Infectious pleural effusion	0/2676 (0%)		1/2674 (0%)
Influenza	5/2676 (0.2%)		4/2674 (0.1%)
Periodontitis	1/2676 (0%)		0/2674 (0%)
Peritonitis	2/2676 (0.1%)		2/2674 (0.1%)
Pneumonia	18/2676 (0.7%)		14/2674 (0.5%)
Pneumonia bacterial	0/2676 (0%)		1/2674 (0%)
Pyelonephritis acute	3/2676 (0.1%)		4/2674 (0.1%)
Sepsis	5/2676 (0.2%)		6/2674 (0.2%)
Tuberculous pleurisy	1/2676 (0%)		0/2674 (0%)
Urinary tract infection	13/2676 (0.5%)		5/2674 (0.2%)
Appendiceal abscess	1/2676 (0%)		0/2674 (0%)
Arthritis bacterial	0/2676 (0%)		2/2674 (0.1%)
Conjunctivitis	1/2676 (0%)		0/2674 (0%)
Cystitis	1/2676 (0%)		0/2674 (0%)
Dengue fever	1/2676 (0%)		0/2674 (0%)
Device related infection	0/2676 (0%)		1/2674 (0%)
Diverticulitis	0/2676 (0%)		1/2674 (0%)
Diverticulitis intestinal haemorrhagic	2/2676 (0.1%)		0/2674 (0%)
Ear infection	1/2676 (0%)		0/2674 (0%)
Endocarditis	0/2676 (0%)		2/2674 (0.1%)
Epididymitis	1/2676 (0%)		0/2674 (0%)
Gangrene	0/2676 (0%)		2/2674 (0.1%)
Gastroenteritis	3/2676 (0.1%)		2/2674 (0.1%)
Gastroenteritis norovirus	1/2676 (0%)		1/2674 (0%)
Haematoma infection	1/2676 (0%)		0/2674 (0%)
Herpes zoster	1/2676 (0%)		0/2674 (0%)
Infection	2/2676 (0.1%)		0/2674 (0%)
Leptospirosis	0/2676 (0%)		1/2674 (0%)
Meningitis bacterial	1/2676 (0%)		0/2674 (0%)
Mycotoxicosis	0/2676 (0%)		1/2674 (0%)
Neuroborreliosis	1/2676 (0%)		0/2674 (0%)
Neurosyphilis	1/2676 (0%)		0/2674 (0%)
Orchitis	1/2676 (0%)		0/2674 (0%)
Osteomyelitis	0/2676 (0%)		2/2674 (0.1%)
Otitis media acute	1/2676 (0%)		0/2674 (0%)
Parotitis	0/2676 (0%)		1/2674 (0%)
Perineal abscess	1/2676 (0%)		0/2674 (0%)
Perirectal abscess	1/2676 (0%)		0/2674 (0%)
Peritonitis bacterial	0/2676 (0%)		1/2674 (0%)
Peritonsillar abscess	0/2676 (0%)		1/2674 (0%)
Pneumonia viral	0/2676 (0%)		1/2674 (0%)
Postoperative wound infection	1/2676 (0%)		0/2674 (0%)
Pulmonary sepsis	0/2676 (0%)		1/2674 (0%)
Pulpitis dental	0/2676 (0%)		1/2674 (0%)
Pyelonephritis	1/2676 (0%)		1/2674 (0%)
Respiratory tract infection	2/2676 (0.1%)		3/2674 (0.1%)
Septic embolus	0/2676 (0%)		1/2674 (0%)
Septic shock	2/2676 (0.1%)		0/2674 (0%)
Sialoadenitis	1/2676 (0%)		0/2674 (0%)
Thrombophlebitis septic	1/2676 (0%)		0/2674 (0%)
Urosepsis	0/2676 (0%)		1/2674 (0%)
Vestibular neuronitis	1/2676 (0%)		1/2674 (0%)
Injury, poisoning and procedural complications
Airway burns	1/2676 (0%)		0/2674 (0%)
Ankle fracture	4/2676 (0.1%)		2/2674 (0.1%)
Arterial injury	1/2676 (0%)		0/2674 (0%)
Clavicle fracture	0/2676 (0%)		1/2674 (0%)
Contusion	2/2676 (0.1%)		1/2674 (0%)
Fall	21/2676 (0.8%)		9/2674 (0.3%)
Femoral neck fracture	3/2676 (0.1%)		1/2674 (0%)
Femur fracture	3/2676 (0.1%)		2/2674 (0.1%)
Joint injury	1/2676 (0%)		0/2674 (0%)
Laceration	1/2676 (0%)		3/2674 (0.1%)
Ligament sprain	1/2676 (0%)		2/2674 (0.1%)
Meniscus injury	4/2676 (0.1%)		2/2674 (0.1%)
Multiple fractures	1/2676 (0%)		1/2674 (0%)
Near drowning	1/2676 (0%)		0/2674 (0%)
Overdose	1/2676 (0%)		0/2674 (0%)
Postoperative ileus	1/2676 (0%)		0/2674 (0%)
Radius fracture	2/2676 (0.1%)		4/2674 (0.1%)
Rib fracture	4/2676 (0.1%)		1/2674 (0%)
Road traffic accident	2/2676 (0.1%)		2/2674 (0.1%)
Spinal compression fracture	3/2676 (0.1%)		3/2674 (0.1%)
Spinal cord injury	1/2676 (0%)		0/2674 (0%)
Spinal cord injury cervical	0/2676 (0%)		1/2674 (0%)
Spinal fracture	1/2676 (0%)		0/2674 (0%)
Subarachnoid haemorrhage	2/2676 (0.1%)		4/2674 (0.1%)
Subdural haematoma	7/2676 (0.3%)		3/2674 (0.1%)
Subdural haemorrhage	3/2676 (0.1%)		1/2674 (0%)
Thermal burn	1/2676 (0%)		0/2674 (0%)
Tibia fracture	0/2676 (0%)		1/2674 (0%)
Traumatic haemothorax	1/2676 (0%)		0/2674 (0%)
Upper limb fracture	0/2676 (0%)		3/2674 (0.1%)
Wound	1/2676 (0%)		0/2674 (0%)
Wrist fracture	2/2676 (0.1%)		1/2674 (0%)
Acetabulum fracture	1/2676 (0%)		0/2674 (0%)
Alcohol poisoning	1/2676 (0%)		0/2674 (0%)
Cervical vertebral fracture	0/2676 (0%)		2/2674 (0.1%)
Chest injury	1/2676 (0%)		0/2674 (0%)
Concussion	2/2676 (0.1%)		2/2674 (0.1%)
Exposure during pregnancy	1/2676 (0%)		0/2674 (0%)
Facial bones fracture	2/2676 (0.1%)		0/2674 (0%)
Foot fracture	2/2676 (0.1%)		0/2674 (0%)
Fracture	1/2676 (0%)		0/2674 (0%)
Fracture displacement	0/2676 (0%)		1/2674 (0%)
Hand fracture	0/2676 (0%)		2/2674 (0.1%)
Head injury	1/2676 (0%)		0/2674 (0%)
Hip fracture	2/2676 (0.1%)		1/2674 (0%)
Humerus fracture	0/2676 (0%)		2/2674 (0.1%)
Injury	2/2676 (0.1%)		0/2674 (0%)
Intentional overdose	1/2676 (0%)		0/2674 (0%)
Jaw fracture	0/2676 (0%)		1/2674 (0%)
Joint dislocation	1/2676 (0%)		0/2674 (0%)
Ligament rupture	1/2676 (0%)		0/2674 (0%)
Limb injury	0/2676 (0%)		3/2674 (0.1%)
Limb traumatic amputation	0/2676 (0%)		1/2674 (0%)
Lower limb fracture	0/2676 (0%)		1/2674 (0%)
Lumbar vertebral fracture	1/2676 (0%)		0/2674 (0%)
Multiple injuries	0/2676 (0%)		1/2674 (0%)
Muscle strain	0/2676 (0%)		1/2674 (0%)
Pelvic fracture	0/2676 (0%)		1/2674 (0%)
Poisoning deliberate	1/2676 (0%)		0/2674 (0%)
Pubis fracture	1/2676 (0%)		0/2674 (0%)
Pulmonary contusion	1/2676 (0%)		0/2674 (0%)
Scapula fracture	1/2676 (0%)		0/2674 (0%)
Skull fracture	1/2676 (0%)		0/2674 (0%)
Tendon rupture	0/2676 (0%)		1/2674 (0%)
Thoracic vertebral fracture	1/2676 (0%)		1/2674 (0%)
Traumatic intracranial haemorrhage	2/2676 (0.1%)		1/2674 (0%)
Ulna fracture	1/2676 (0%)		1/2674 (0%)
Investigations
Alanine aminotransferase increased	1/2676 (0%)		0/2674 (0%)
Aspartate aminotransferase increased	1/2676 (0%)		0/2674 (0%)
Creatinine renal clearance decreased	1/2676 (0%)		0/2674 (0%)
Bile duct pressure increased	0/2676 (0%)		1/2674 (0%)
Blood creatinine increased	0/2676 (0%)		1/2674 (0%)
Blood glucose increased	1/2676 (0%)		0/2674 (0%)
Blood pressure increased	0/2676 (0%)		1/2674 (0%)
Computerised tomogram thorax abnormal	0/2676 (0%)		1/2674 (0%)
Electrocardiogram Q waves	1/2676 (0%)		0/2674 (0%)
Gamma-glutamyltransferase increased	0/2676 (0%)		1/2674 (0%)
Haemoglobin decreased	0/2676 (0%)		1/2674 (0%)
Influenza A virus test positive	0/2676 (0%)		1/2674 (0%)
Prostatic specific antigen increased	0/2676 (0%)		1/2674 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	3/2676 (0.1%)		0/2674 (0%)
Diabetes mellitus inadequate control	1/2676 (0%)		2/2674 (0.1%)
Hyperglycaemia	1/2676 (0%)		0/2674 (0%)
Hypokalaemia	2/2676 (0.1%)		3/2674 (0.1%)
Hyponatraemia	2/2676 (0.1%)		2/2674 (0.1%)
Type 2 diabetes mellitus	1/2676 (0%)		2/2674 (0.1%)
Dehydration	1/2676 (0%)		1/2674 (0%)
Gout	0/2676 (0%)		1/2674 (0%)
Hypoglycaemia	0/2676 (0%)		1/2674 (0%)
Hypovolaemia	1/2676 (0%)		0/2674 (0%)
Lactic acidosis	1/2676 (0%)		0/2674 (0%)
Metabolic acidosis	1/2676 (0%)		0/2674 (0%)
Obesity	0/2676 (0%)		1/2674 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/2676 (0.1%)		2/2674 (0.1%)
Back pain	3/2676 (0.1%)		2/2674 (0.1%)
Diffuse idiopathic skeletal hyperostosis	1/2676 (0%)		0/2674 (0%)
Fracture nonunion	1/2676 (0%)		0/2674 (0%)
Intervertebral disc degeneration	0/2676 (0%)		1/2674 (0%)
Intervertebral disc protrusion	3/2676 (0.1%)		4/2674 (0.1%)
Lumbar spinal stenosis	1/2676 (0%)		1/2674 (0%)
Osteoarthritis	12/2676 (0.4%)		19/2674 (0.7%)
Osteonecrosis	1/2676 (0%)		1/2674 (0%)
Rotator cuff syndrome	3/2676 (0.1%)		0/2674 (0%)
Systemic lupus erythematosus	0/2676 (0%)		1/2674 (0%)
Arthritis	2/2676 (0.1%)		0/2674 (0%)
Bursitis	0/2676 (0%)		1/2674 (0%)
Cervical spinal stenosis	0/2676 (0%)		2/2674 (0.1%)
Foot deformity	1/2676 (0%)		1/2674 (0%)
Groin pain	0/2676 (0%)		1/2674 (0%)
Haemarthrosis	2/2676 (0.1%)		1/2674 (0%)
Intervertebral disc disorder	0/2676 (0%)		1/2674 (0%)
Jaw cyst	0/2676 (0%)		1/2674 (0%)
Joint stiffness	1/2676 (0%)		0/2674 (0%)
Limb discomfort	0/2676 (0%)		1/2674 (0%)
Meniscal degeneration	1/2676 (0%)		0/2674 (0%)
Mobility decreased	0/2676 (0%)		1/2674 (0%)
Muscle haemorrhage	1/2676 (0%)		0/2674 (0%)
Muscular weakness	0/2676 (0%)		1/2674 (0%)
Musculoskeletal chest pain	2/2676 (0.1%)		2/2674 (0.1%)
Musculoskeletal pain	2/2676 (0.1%)		1/2674 (0%)
Necrotising myositis	0/2676 (0%)		1/2674 (0%)
Osteitis	1/2676 (0%)		0/2674 (0%)
Osteoporotic fracture	1/2676 (0%)		0/2674 (0%)
Polymyalgia rheumatica	2/2676 (0.1%)		1/2674 (0%)
Pseudarthrosis	0/2676 (0%)		1/2674 (0%)
Psoriatic arthropathy	1/2676 (0%)		0/2674 (0%)
Rhabdomyolysis	1/2676 (0%)		1/2674 (0%)
Spinal osteoarthritis	0/2676 (0%)		1/2674 (0%)
Synovial cyst	1/2676 (0%)		0/2674 (0%)
Systemic scleroderma	1/2676 (0%)		0/2674 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenoma benign	0/2676 (0%)		1/2674 (0%)
Basal cell carcinoma	9/2676 (0.3%)		12/2674 (0.4%)
Bowen's disease	2/2676 (0.1%)		2/2674 (0.1%)
Brain neoplasm	1/2676 (0%)		3/2674 (0.1%)
Brain neoplasm malignant	0/2676 (0%)		1/2674 (0%)
Breast cancer	1/2676 (0%)		1/2674 (0%)
Carcinoid tumour	1/2676 (0%)		0/2674 (0%)
Cerebellar haemangioma	0/2676 (0%)		1/2674 (0%)
Cholangiocarcinoma	2/2676 (0.1%)		1/2674 (0%)
Colon adenoma	0/2676 (0%)		2/2674 (0.1%)
Colon cancer	8/2676 (0.3%)		2/2674 (0.1%)
Colon cancer stage IV	0/2676 (0%)		1/2674 (0%)
Colon neoplasm	1/2676 (0%)		0/2674 (0%)
Endometrial cancer	1/2676 (0%)		0/2674 (0%)
Gastric adenoma	1/2676 (0%)		0/2674 (0%)
Gastric cancer	3/2676 (0.1%)		3/2674 (0.1%)
Glioblastoma multiforme	2/2676 (0.1%)		1/2674 (0%)
Hepatocellular carcinoma	0/2676 (0%)		1/2674 (0%)
Hypopharyngeal cancer	1/2676 (0%)		0/2674 (0%)
Laryngeal cancer stage 0	0/2676 (0%)		1/2674 (0%)
Lip and/or oral cavity cancer	0/2676 (0%)		1/2674 (0%)
Lung neoplasm malignant	2/2676 (0.1%)		1/2674 (0%)
Malignant melanoma	2/2676 (0.1%)		2/2674 (0.1%)
Myelodysplastic syndrome	1/2676 (0%)		1/2674 (0%)
Papillary thyroid cancer	3/2676 (0.1%)		1/2674 (0%)
Plasma cell myeloma	0/2676 (0%)		1/2674 (0%)
Prostate cancer	7/2676 (0.3%)		6/2674 (0.2%)
Uterine leiomyoma	1/2676 (0%)		0/2674 (0%)
Adenocarcinoma of colon	1/2676 (0%)		3/2674 (0.1%)
B-cell lymphoma	0/2676 (0%)		1/2674 (0%)
Bladder cancer	1/2676 (0%)		2/2674 (0.1%)
Bladder cancer recurrent	1/2676 (0%)		0/2674 (0%)
Bladder neoplasm	1/2676 (0%)		1/2674 (0%)
Bladder transitional cell carcinoma	1/2676 (0%)		0/2674 (0%)
Breast cancer recurrent	0/2676 (0%)		1/2674 (0%)
Clear cell renal cell carcinoma	0/2676 (0%)		1/2674 (0%)
Colon cancer metastatic	1/2676 (0%)		0/2674 (0%)
Colorectal cancer	0/2676 (0%)		1/2674 (0%)
Duodenal neoplasm	0/2676 (0%)		1/2674 (0%)
Endometrial adenocarcinoma	1/2676 (0%)		0/2674 (0%)
Essential thrombocythaemia	0/2676 (0%)		1/2674 (0%)
Invasive breast carcinoma	0/2676 (0%)		1/2674 (0%)
Laryngeal cancer	0/2676 (0%)		2/2674 (0.1%)
Lung adenocarcinoma	0/2676 (0%)		2/2674 (0.1%)
Lung neoplasm	0/2676 (0%)		1/2674 (0%)
Malignant melanoma in situ	1/2676 (0%)		0/2674 (0%)
Metastases to liver	0/2676 (0%)		1/2674 (0%)
Metastases to lung	0/2676 (0%)		2/2674 (0.1%)
Metastases to lymph nodes	0/2676 (0%)		1/2674 (0%)
Metastatic bronchial carcinoma	1/2676 (0%)		0/2674 (0%)
Metastatic malignant melanoma	1/2676 (0%)		0/2674 (0%)
Myelofibrosis	1/2676 (0%)		0/2674 (0%)
Myeloproliferative neoplasm	0/2676 (0%)		1/2674 (0%)
Non-Hodgkin's lymphoma	1/2676 (0%)		0/2674 (0%)
Oesophageal squamous cell carcinoma	0/2676 (0%)		1/2674 (0%)
Ovarian adenoma	0/2676 (0%)		1/2674 (0%)
Ovarian epithelial cancer metastatic	1/2676 (0%)		0/2674 (0%)
Polycythaemia vera	0/2676 (0%)		1/2674 (0%)
Prostate cancer recurrent	0/2676 (0%)		1/2674 (0%)
Prostatic adenoma	1/2676 (0%)		0/2674 (0%)
Rectal cancer	0/2676 (0%)		1/2674 (0%)
Renal cancer	0/2676 (0%)		2/2674 (0.1%)
Renal cell carcinoma recurrent	0/2676 (0%)		1/2674 (0%)
Skin cancer	1/2676 (0%)		0/2674 (0%)
Small intestine carcinoma	0/2676 (0%)		1/2674 (0%)
Squamous cell carcinoma	3/2676 (0.1%)		1/2674 (0%)
Squamous cell carcinoma of skin	0/2676 (0%)		2/2674 (0.1%)
Squamous cell carcinoma of the vulva	1/2676 (0%)		0/2674 (0%)
Thymoma	0/2676 (0%)		1/2674 (0%)
Transitional cell carcinoma	1/2676 (0%)		0/2674 (0%)
Tumour obstruction	0/2676 (0%)		1/2674 (0%)
Nervous system disorders
Brain stem infarction	1/2676 (0%)		0/2674 (0%)
Cerebellar infarction	0/2676 (0%)		3/2674 (0.1%)
Cerebral haemorrhage	1/2676 (0%)		0/2674 (0%)
Cerebral infarction	25/2676 (0.9%)		42/2674 (1.6%)
Cerebrovascular accident	95/2676 (3.6%)		97/2674 (3.6%)
Diplegia	0/2676 (0%)		1/2674 (0%)
Embolic cerebral infarction	0/2676 (0%)		1/2674 (0%)
Embolic stroke	1/2676 (0%)		2/2674 (0.1%)
Epilepsy	18/2676 (0.7%)		25/2674 (0.9%)
Haemorrhagic cerebral infarction	1/2676 (0%)		1/2674 (0%)
Headache	3/2676 (0.1%)		3/2674 (0.1%)
Hemianaesthesia	2/2676 (0.1%)		2/2674 (0.1%)
Hemiparesis	5/2676 (0.2%)		3/2674 (0.1%)
Hypoaesthesia	1/2676 (0%)		4/2674 (0.1%)
Intracranial aneurysm	1/2676 (0%)		0/2674 (0%)
Ischaemic cerebral infarction	1/2676 (0%)		2/2674 (0.1%)
Ischaemic stroke	47/2676 (1.8%)		45/2674 (1.7%)
Lacunar infarction	0/2676 (0%)		1/2674 (0%)
Multiple sclerosis	1/2676 (0%)		0/2674 (0%)
Muscle spasticity	0/2676 (0%)		1/2674 (0%)
Post stroke seizure	3/2676 (0.1%)		0/2674 (0%)
Seizure	17/2676 (0.6%)		16/2674 (0.6%)
Temporal lobe epilepsy	0/2676 (0%)		1/2674 (0%)
Thrombotic cerebral infarction	0/2676 (0%)		1/2674 (0%)
Transient ischaemic attack	46/2676 (1.7%)		41/2674 (1.5%)
Vertebrobasilar insufficiency	1/2676 (0%)		2/2674 (0.1%)
Aphasia	2/2676 (0.1%)		2/2674 (0.1%)
Ataxia	1/2676 (0%)		0/2674 (0%)
Brain injury	1/2676 (0%)		0/2674 (0%)
Brain stem stroke	1/2676 (0%)		0/2674 (0%)
Carotid arteriosclerosis	1/2676 (0%)		0/2674 (0%)
Carotid artery aneurysm	1/2676 (0%)		0/2674 (0%)
Carotid artery stenosis	3/2676 (0.1%)		3/2674 (0.1%)
Carpal tunnel syndrome	0/2676 (0%)		1/2674 (0%)
Central pain syndrome	1/2676 (0%)		0/2674 (0%)
Cerebellar stroke	1/2676 (0%)		0/2674 (0%)
Cerebral cyst	0/2676 (0%)		1/2674 (0%)
Cerebral ischaemia	1/2676 (0%)		1/2674 (0%)
Cerebral vasoconstriction	1/2676 (0%)		0/2674 (0%)
Cervicobrachial syndrome	1/2676 (0%)		0/2674 (0%)
Cervicogenic headache	0/2676 (0%)		1/2674 (0%)
Cubital tunnel syndrome	0/2676 (0%)		1/2674 (0%)
Dementia	1/2676 (0%)		2/2674 (0.1%)
Diabetic neuropathy	1/2676 (0%)		0/2674 (0%)
Dizziness	8/2676 (0.3%)		4/2674 (0.1%)
Dizziness postural	1/2676 (0%)		0/2674 (0%)
Encephalopathy	2/2676 (0.1%)		1/2674 (0%)
Facial paralysis	0/2676 (0%)		3/2674 (0.1%)
Facial paresis	0/2676 (0%)		1/2674 (0%)
Focal dyscognitive seizures	1/2676 (0%)		0/2674 (0%)
Generalised tonic-clonic seizure	2/2676 (0.1%)		1/2674 (0%)
Guillain-Barre syndrome	0/2676 (0%)		1/2674 (0%)
Haemorrhage intracranial	1/2676 (0%)		1/2674 (0%)
Haemorrhagic stroke	1/2676 (0%)		0/2674 (0%)
Haemorrhagic transformation stroke	1/2676 (0%)		0/2674 (0%)
Hypertensive encephalopathy	0/2676 (0%)		1/2674 (0%)
Hypoglycaemic coma	1/2676 (0%)		0/2674 (0%)
Hypoxic-ischaemic encephalopathy	0/2676 (0%)		1/2674 (0%)
Loss of consciousness	1/2676 (0%)		0/2674 (0%)
Memory impairment	0/2676 (0%)		1/2674 (0%)
Metabolic encephalopathy	1/2676 (0%)		0/2674 (0%)
Migraine	2/2676 (0.1%)		2/2674 (0.1%)
Migraine with aura	1/2676 (0%)		1/2674 (0%)
Monoparesis	1/2676 (0%)		0/2674 (0%)
Monoplegia	0/2676 (0%)		1/2674 (0%)
Neuralgia	1/2676 (0%)		1/2674 (0%)
Neuralgic amyotrophy	1/2676 (0%)		0/2674 (0%)
Neurodegenerative disorder	0/2676 (0%)		1/2674 (0%)
Neuroglycopenia	1/2676 (0%)		0/2674 (0%)
Neurological symptom	0/2676 (0%)		2/2674 (0.1%)
Neuropathy peripheral	1/2676 (0%)		1/2674 (0%)
Paraesthesia	2/2676 (0.1%)		2/2674 (0.1%)
Partial seizures	5/2676 (0.2%)		5/2674 (0.2%)
Polyneuropathy	0/2676 (0%)		1/2674 (0%)
Post stroke epilepsy	2/2676 (0.1%)		2/2674 (0.1%)
Presyncope	1/2676 (0%)		0/2674 (0%)
Pseudostroke	0/2676 (0%)		1/2674 (0%)
Radial nerve compression	0/2676 (0%)		1/2674 (0%)
Sciatica	2/2676 (0.1%)		2/2674 (0.1%)
Sensory disturbance	0/2676 (0%)		1/2674 (0%)
Sensory loss	1/2676 (0%)		0/2674 (0%)
Status epilepticus	3/2676 (0.1%)		1/2674 (0%)
Syncope	8/2676 (0.3%)		6/2674 (0.2%)
Tonic convulsion	0/2676 (0%)		1/2674 (0%)
Transient global amnesia	0/2676 (0%)		2/2674 (0.1%)
Visual field defect	0/2676 (0%)		1/2674 (0%)
Vocal cord paralysis	0/2676 (0%)		2/2674 (0.1%)
Product Issues
Device dislocation	0/2676 (0%)		1/2674 (0%)
Psychiatric disorders
Adjustment disorder	1/2676 (0%)		1/2674 (0%)
Anxiety	1/2676 (0%)		2/2674 (0.1%)
Bipolar disorder	0/2676 (0%)		1/2674 (0%)
Completed suicide	1/2676 (0%)		1/2674 (0%)
Delirium	5/2676 (0.2%)		2/2674 (0.1%)
Depression	7/2676 (0.3%)		4/2674 (0.1%)
Major depression	1/2676 (0%)		0/2674 (0%)
Suicidal ideation	2/2676 (0.1%)		3/2674 (0.1%)
Aggression	0/2676 (0%)		1/2674 (0%)
Alcohol withdrawal syndrome	1/2676 (0%)		0/2674 (0%)
Bipolar I disorder	0/2676 (0%)		1/2674 (0%)
Confusional state	2/2676 (0.1%)		1/2674 (0%)
Generalised anxiety disorder	1/2676 (0%)		0/2674 (0%)
Hallucination	0/2676 (0%)		2/2674 (0.1%)
Mental status changes	1/2676 (0%)		0/2674 (0%)
Panic attack	1/2676 (0%)		1/2674 (0%)
Post stroke depression	0/2676 (0%)		1/2674 (0%)
Schizophrenia	0/2676 (0%)		1/2674 (0%)
Somatic symptom disorder	0/2676 (0%)		1/2674 (0%)
Renal and urinary disorders
Acute kidney injury	8/2676 (0.3%)		10/2674 (0.4%)
Diabetic nephropathy	1/2676 (0%)		0/2674 (0%)
Hydronephrosis	2/2676 (0.1%)		0/2674 (0%)
Nephrolithiasis	6/2676 (0.2%)		5/2674 (0.2%)
Pollakiuria	0/2676 (0%)		1/2674 (0%)
Postrenal failure	1/2676 (0%)		0/2674 (0%)
Ureterolithiasis	0/2676 (0%)		4/2674 (0.1%)
Anuria	0/2676 (0%)		1/2674 (0%)
Calculus bladder	3/2676 (0.1%)		0/2674 (0%)
Calculus urinary	3/2676 (0.1%)		0/2674 (0%)
Chronic kidney disease	0/2676 (0%)		1/2674 (0%)
Glomerulonephritis proliferative	0/2676 (0%)		1/2674 (0%)
Haematuria	6/2676 (0.2%)		3/2674 (0.1%)
Renal colic	1/2676 (0%)		3/2674 (0.1%)
Renal failure	4/2676 (0.1%)		1/2674 (0%)
Renal impairment	0/2676 (0%)		2/2674 (0.1%)
Renal ischaemia	0/2676 (0%)		1/2674 (0%)
Renal mass	0/2676 (0%)		1/2674 (0%)
Renal tubular necrosis	1/2676 (0%)		0/2674 (0%)
Ureteric obstruction	0/2676 (0%)		1/2674 (0%)
Urethral stenosis	0/2676 (0%)		1/2674 (0%)
Urinary retention	1/2676 (0%)		0/2674 (0%)
Urinary tract obstruction	1/2676 (0%)		0/2674 (0%)
Urogenital haemorrhage	1/2676 (0%)		0/2674 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	5/2676 (0.2%)		3/2674 (0.1%)
Prostatitis	2/2676 (0.1%)		0/2674 (0%)
Vaginal haemorrhage	2/2676 (0.1%)		1/2674 (0%)
Acquired hydrocele	1/2676 (0%)		0/2674 (0%)
Balanoposthitis	0/2676 (0%)		1/2674 (0%)
Breast mass	0/2676 (0%)		1/2674 (0%)
Cervical dysplasia	0/2676 (0%)		1/2674 (0%)
Cervical polyp	1/2676 (0%)		0/2674 (0%)
Menorrhagia	3/2676 (0.1%)		0/2674 (0%)
Spermatocele	1/2676 (0%)		0/2674 (0%)
Uterine polyp	1/2676 (0%)		0/2674 (0%)
Uterine prolapse	1/2676 (0%)		0/2674 (0%)
Vaginal polyp	1/2676 (0%)		0/2674 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/2676 (0%)		1/2674 (0%)
Bronchitis chronic	1/2676 (0%)		0/2674 (0%)
Chronic obstructive pulmonary disease	6/2676 (0.2%)		6/2674 (0.2%)
Dyspnoea exertional	1/2676 (0%)		1/2674 (0%)
Emphysema	0/2676 (0%)		1/2674 (0%)
Sleep apnoea syndrome	3/2676 (0.1%)		0/2674 (0%)
Alveolitis allergic	0/2676 (0%)		1/2674 (0%)
Atelectasis	0/2676 (0%)		1/2674 (0%)
Bronchopneumopathy	1/2676 (0%)		0/2674 (0%)
Dyspnoea	8/2676 (0.3%)		1/2674 (0%)
Hypoxia	0/2676 (0%)		1/2674 (0%)
Interstitial lung disease	1/2676 (0%)		0/2674 (0%)
Laryngeal oedema	1/2676 (0%)		0/2674 (0%)
Nasal polyps	0/2676 (0%)		1/2674 (0%)
Pleural effusion	1/2676 (0%)		2/2674 (0.1%)
Pleurisy	0/2676 (0%)		1/2674 (0%)
Pneumonia aspiration	0/2676 (0%)		1/2674 (0%)
Pulmonary alveolar haemorrhage	1/2676 (0%)		0/2674 (0%)
Pulmonary congestion	0/2676 (0%)		1/2674 (0%)
Pulmonary embolism	0/2676 (0%)		7/2674 (0.3%)
Pulmonary fibrosis	0/2676 (0%)		3/2674 (0.1%)
Pulmonary oedema	1/2676 (0%)		0/2674 (0%)
Respiratory failure	2/2676 (0.1%)		4/2674 (0.1%)
Tachypnoea	0/2676 (0%)		1/2674 (0%)
Skin and subcutaneous tissue disorders
Eczema	1/2676 (0%)		0/2674 (0%)
Haemorrhage subcutaneous	0/2676 (0%)		1/2674 (0%)
Angioedema	1/2676 (0%)		0/2674 (0%)
Dermatitis atopic	0/2676 (0%)		1/2674 (0%)
Hypersensitivity vasculitis	2/2676 (0.1%)		0/2674 (0%)
Nail disorder	0/2676 (0%)		1/2674 (0%)
Psoriasis	1/2676 (0%)		0/2674 (0%)
Purpura	1/2676 (0%)		0/2674 (0%)
Skin ulcer	2/2676 (0.1%)		0/2674 (0%)
Social circumstances
Tanning	1/2676 (0%)		0/2674 (0%)
Surgical and medical procedures
Cardiac pacemaker insertion	0/2676 (0%)		1/2674 (0%)
Hysterectomy	0/2676 (0%)		1/2674 (0%)
Myomectomy	1/2676 (0%)		0/2674 (0%)
Tooth extraction	1/2676 (0%)		0/2674 (0%)
Vascular disorders
Deep vein thrombosis	4/2676 (0.1%)		9/2674 (0.3%)
Ischaemia	0/2676 (0%)		3/2674 (0.1%)
Peripheral artery occlusion	1/2676 (0%)		5/2674 (0.2%)
Aortic aneurysm	0/2676 (0%)		2/2674 (0.1%)
Aortic occlusion	0/2676 (0%)		1/2674 (0%)
Aortic stenosis	0/2676 (0%)		1/2674 (0%)
Arteriosclerosis	0/2676 (0%)		1/2674 (0%)
Arteritis	1/2676 (0%)		0/2674 (0%)
Blue toe syndrome	1/2676 (0%)		0/2674 (0%)
Circulatory collapse	2/2676 (0.1%)		1/2674 (0%)
Embolism	1/2676 (0%)		0/2674 (0%)
Extremity necrosis	1/2676 (0%)		0/2674 (0%)
Hypertension	4/2676 (0.1%)		0/2674 (0%)
Hypertensive crisis	11/2676 (0.4%)		4/2674 (0.1%)
Hypotension	0/2676 (0%)		2/2674 (0.1%)
Iliac artery occlusion	0/2676 (0%)		1/2674 (0%)
Orthostatic hypotension	1/2676 (0%)		0/2674 (0%)
Peripheral arterial occlusive disease	1/2676 (0%)		4/2674 (0.1%)
Peripheral artery stenosis	0/2676 (0%)		1/2674 (0%)
Peripheral ischaemia	1/2676 (0%)		3/2674 (0.1%)
Shock haemorrhagic	0/2676 (0%)		1/2674 (0%)
Thrombophlebitis	0/2676 (0%)		1/2674 (0%)
Varicose vein	0/2676 (0%)		1/2674 (0%)
Vasospasm	1/2676 (0%)		0/2674 (0%)
Other (Not Including Serious) Adverse Events
	Dabigatran Etexilate 110 or 150 Milligram (mg)		Acetylsalicylic Acid, Aspirin (ASA) 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	306/2676 (11.4%)		295/2674 (11%)
Cardiac disorders
Atrial fibrillation	136/2676 (5.1%)		128/2674 (4.8%)
Infections and infestations
Nasopharyngitis	173/2676 (6.5%)		170/2674 (6.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.

Results Point of Contact

Name/Title	Boehringer Ingelheim, Call Centre
Organization	Boehringer Ingelheim
Phone	1-800-243-0127
Email	clintriage.rdg@boehringer-ingelheim.com

Responsible Party:

Boehringer Ingelheim

ClinicalTrials.gov Identifier:

NCT02239120

Other Study ID Numbers:

1160.189
2013-003444-24

First Posted:

Sep 12, 2014

Last Update Posted:

Sep 6, 2019

Last Verified:

Aug 1, 2019

Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source (RE-SPECT ESUS)

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion criteria:

Exclusion criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Additional Information:

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact