Long-term, Open-label Follow-up Treatment of Patients With A-fib Who Have Been Previously Treated With BIBR 1048

Sponsor

Boehringer Ingelheim (Industry)

Overall Status

Terminated

CT.gov ID

NCT00157248

Collaborator

(none)

361

Enrollment

Locations

Arms

7.2

Patients Per Site

Study Details

Study Description

Brief Summary

To determine the long term safety and efficacy of BIBR 1048 in patients with chronic atrial fibrilla tion, with or without concomitant chronic treatment with acetylsalicylic acid (ASA).

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation Stroke	Drug: dabigatran etexilate Drug: dabigatran etexilate Drug: dabigatran etexilate Drug: dabigatran etexilate	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

361 participants

Allocation:

Non-Randomized

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Long-term, Open-label Follow-up Treatment of Patients With Atrial Fibrillation Who Have Been Previously Treated With BIBR 1048 in the PETRO Trial (Trial 1160.20 - NCT01227629). (PETRO Extension Trial: PETRO-Ex)

Study Start Date :

Dec 1, 2003

Actual Primary Completion Date :

Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: dabigatran etexilate, 150 mg once daily dosage used at study start	Drug: dabigatran etexilate dosage used at study start
Experimental: dabigatran etexilate, 150 mg twice daily dosage used at study start	Drug: dabigatran etexilate dosage used at study start
Experimental: dabigatran etexilate, 300 mg once daily dosage used at study start	Drug: dabigatran etexilate dosage used at study start
Experimental: dabigatran etexilate, 300 mg twice daily dosage used at study start	Drug: dabigatran etexilate dosage used at study start

Outcome Measures

Primary Outcome Measures

Yearly Event Rate for Composite Endpoint of Stroke, Transient Ischaemic Attacks, System Thromboembolism, Myocardial Infarction, Other Major Adverse Cardiac Events and Mortality. [5 years]
Time to first occurrence of stroke, transient ischaemic attacks, system thromboembolism, myocardial infarction, other major adverse cardiac events and mortality. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate for Major Bleeding [5 years]
Time to first occurrence of fatal or life-threatening, retroperitoneal, intracranial, intraocular, or intraspinal bleeding, which required surgical treatment, led to a transfusion of a minimum of 2 units of packed cells or whole blood, or led to a fall in hemoglobin of 20g/L or less. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate for Major + Minor/Relevant Bleeding [5 years]
Time to first occurrence of either major or minor/relevant bleeding. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate for Any Bleeding [5 years]
Time to first occurrence of any bleeding event. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate for Minor Bleeding [5 years]
Time to first occurrence of minor bleeding. A minor bleeding event is any bleed that does not qualify as a major bleed. All minor bleeding events not fulfilling one of the criteria for clinically relevant were classified as nuisance bleeds. Clinically-relevant was defined as spontaneous skin hematoma ≥25 cm², spontaneous nose bleed >5 min, macroscopic hematuria spontaneous or lasting longer than 24 hours if associated with an intervention, spontaneous rectal bleeding, gingival bleeding >5 min, leading to hospitalization, leading to a transfusion of <2 units of packed cells or whole blood and any other bleeding event considered clinically relevant by the investigator. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25

Secondary Outcome Measures

Yearly Event Rate for Stroke [5 years]
Time to first occurrence of any fatal or non-fatal stroke. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate of Ischaemic Stroke [5 years]
Time to first occurrence of any ischaemic stroke. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate of Haemorrhagic Stroke [5 years]
Time to first occurrence of any haemorrhagic stroke. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate for Transient Ischaemic Attacks [5 years]
Time to first occurrence of any transient ischaemic attacks. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate for Systemic Thromboembolism [5 years]
Time to first occurrence of any non-central nervous system systemic thromboembolism. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate of Myocardial Infarction [5 years]
Time to first occurrence of any myocardial infarction. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate of Other Major Adverse Cardiac Events [5 years]
Time to first occurrence of any other major adverse cardiac events. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate of Death [5 years]
Time to death of any cause. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate for Composite Secondary Endpoint of Ischaemic Stroke, Transient Ischaemic Attacks, Non-central Nervous System Systemic Thromboembolism, Myocardial Infarction, Other Major Adverse Cardiac Events and All-cause Mortality [5 years]
Time to first occurrence of ischaemic stroke, transient ischaemic attacks, non-central nervous system systemic thromboembolism, myocardial infarction, other major adverse cardiac events and all-cause mortality. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Severe Adverse Event [5 years]
Frequency of patients with severe adverse events.
Laboratory Analyses [5 years]
Frequency of patients with possible clinically significant abnormalities, i.e. with values out of normal range. Normal ranges are defined as: Alanine aminotransferase (ALT): 5-45 [U/L] Aspartate aminotransferase (AST): 10-40 [U/L] Bilirubin, total: 0.2-1.0 [mg/dL]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria Diagnosis and main criteria for inclusion: Paroxysmal, persistent, or permanent (chronic) non-rheumatic atrial fibrillation with a history of coronary artery disease (CAD)

Inclusion Criteria:

previous treatment with BIBR 1048 in PETRO (trial 1160.20- NCT01227629) and no premature discontinuation of therapy
paroxysmal, persistent, or permanent (chronic) non-rheumatic atrial fibrillation, documented by electrocardiogram (ECG) at least twice prior to enrollment in PETRO
concomitant coronary artery disease -an additional risk factor for stroke (one or more of the following conditions/events): hypertension, diabetes mellitus (DM), congestive heart failure (CHF) or Left ventricular dysfunction (LVD), previous ischemic stroke or transient ischemic attack) TIA, or age greater than 75 years. -age >= 18 years
written, informed consent

Exclusion criteria

Exclusion Criteria:

Valvular heart disease conferring significantly increased risk of thromboembolic events (e.g. clinically significant mitral stenosis or prosthetic valves). planned cardioversion while patients are in the study.
contraindication to anticoagulant therapy (previous intracranial hemorrhage, gastro-intestinal (GI) hemorrhage within previous 3 months, previous severe hemorrhage with warfarin at therapeutic international normalized ratio (INR), regular use of non-steroidal anti-inflammatory drugs, hemorrhagic diathesis) major bleeding within the last 6 months (other than GI hemorrhage).
severe renal impairment (estimated glomerular filtration rate [GFR] <= 30 mL/min). uncontrolled hypertension (systolic blood pressure [SBP] > 180 mm Hg and/or diastolic blood pressure [DBP] > 100 mmHg).
Women who are pregnant or of childbearing potential who refuse to use a medically acceptable form of contraception throughout the study (note: a negative pregnancy test must be obtained for any woman of childbearing potential prior to entry into the study).
Patients who have received an investigational drug other than BIBR 1048 within the last 30 days.
Patients considered unreliable by the investigator concerning the requirements for follow-up during the study and/or compliance with study drug administration. Another indication for anticoagulant treatment (eg, deep vein thrombosis or pulmonary embolus). Clinically significant anemia (note: patients with mild-moderate anemia should only be enrolled after the possibility of a GI bleeding source has been evaluated, the etiology of the anemia identified, and appropriate action taken). Patients suffering from thrombocytopenia (platelets < 100,000/uL). Any other condition which, in the discretion of the investigator, would not allow safe participation in the study.
Continuing or planned concomitant treatment with antiplatelet agents other than acetylsalicylic acid (ASA).
Recent malignancy or radiation therapy (<= 6 months).

Contacts and Locations

Locations

	Site	City	State	Country
1	1160.42.10003 Boehringer Ingelheim Investigational Site	La Mesa	California	United States
2	1160.42.10006 Boehringer Ingelheim Investigational Site	Pensacola	Florida	United States
3	1160.42.10004 Boehringer Ingelheim Investigational Site	Port Charlotte	Florida	United States
4	1160.42.10002 Boehringer Ingelheim Investigational Site	St. Petersburg	Florida	United States
5	1160.42.10015 Boehringer Ingelheim Investigational Site	Baltimore	Maryland	United States
6	1160.42.10008 Boehringer Ingelheim Investigational Site	Westminster	Maryland	United States
7	1160.42.10012 Boehringer Ingelheim Investigational Site	Pittsfield	Massachusetts	United States
8	1160.42.10007 Boehringer Ingelheim Investigational Site	Troy	Michigan	United States
9	1160.42.10014 Boehringer Ingelheim Investigational Site	Hawthorne	New York	United States
10	1160.42.10013 Boehringer Ingelheim Investigational Site	New Hyde Park	New York	United States
11	1160.42.10009 Boehringer Ingelheim Investigational Site	North Durham	North Carolina	United States
12	1160.42.10001 Boehringer Ingelheim Investigational Site	Philadelphia	Pennsylvania	United States
13	1160.42.45010 Boehringer Ingelheim Investigational Site	Aalborg		Denmark
14	1160.42.45005 Boehringer Ingelheim Investigational Site	Aarhus C		Denmark
15	1160.42.45007 Boehringer Ingelheim Investigational Site	Brædstrup		Denmark
16	1160.42.45011 Boehringer Ingelheim Investigational Site	Esbjerg		Denmark
17	1160.42.45012 Boehringer Ingelheim Investigational Site	Frederikssund		Denmark
18	1160.42.45003 Boehringer Ingelheim Investigational Site	Helsingør		Denmark
19	1160.42.45004 Boehringer Ingelheim Investigational Site	Herlev		Denmark
20	1160.42.45009 Boehringer Ingelheim Investigational Site	Holbæk		Denmark
21	1160.42.45002 Boehringer Ingelheim Investigational Site	Hvidovre		Denmark
22	1160.42.45014 Boehringer Ingelheim Investigational Site	Køge		Denmark
23	1160.42.45001 Boehringer Ingelheim Investigational Site	Odense		Denmark
24	1160.42.45013 Roskilde Sygehus	Roskilde		Denmark
25	1160.42.45006 Boehringer Ingelheim Investigational Site	Svendborg		Denmark
26	1160.42.31003 Ziekenhuis Amstelveen	Amstelveen		Netherlands
27	1160.42.31001 Academisch Medisch Centrum	Amsterdam		Netherlands
28	1160.42.31013 Onze Lieve Vrouwe Gasthuis	Amsterdam		Netherlands
29	1160.42.31008 Gelre Ziekenhuis, locatie Juliana	Apeldoorn		Netherlands
30	1160.42.31006 Wilhelmina Ziekenhuis	Assen		Netherlands
31	1160.42.31007 Gemini Ziekenhuis	Den Helder		Netherlands
32	1160.42.31002 Ziekenhuis Gelderse Vallei	Ede		Netherlands
33	1160.42.31014 Ziekenhuisgroep Twente	Hengelo		Netherlands
34	1160.42.31012 Vasculair onderzoekscentrum (VOC)	Hoorn		Netherlands
35	1160.42.31009 Havenziekenhuis	Rotterdam		Netherlands
36	1160.42.31004 Maasland Ziekenhuis	Sittard		Netherlands
37	1160.42.31005 Tweesteden Ziekenhuis	Tilburg		Netherlands
38	1160.42.31011 Maxima Medisch Centrum	Veldhoven		Netherlands
39	1160.42.46013 Boehringer Ingelheim Investigational Site	Eskilstuna		Sweden
40	1160.42.46007 Boehringer Ingelheim Investigational Site	Falun		Sweden
41	1160.42.46005 Boehringer Ingelheim Investigational Site	Jönköping		Sweden
42	1160.42.46010 Boehringer Ingelheim Investigational Site	Kalmar		Sweden
43	1160.42.46009 Boehringer Ingelheim Investigational Site	Malmö		Sweden
44	1160.42.46008 Boehringer Ingelheim Investigational Site	Norrköping		Sweden
45	1160.42.46002 Boehringer Ingelheim Investigational Site	Stockholm		Sweden
46	1160.42.46011 Boehringer Ingelheim Investigational Site	Stockholm		Sweden
47	1160.42.46006 Boehringer Ingelheim Investigational Site	Umeaa		Sweden
48	1160.42.46001 Boehringer Ingelheim Investigational Site	Uppsala		Sweden
49	1160.42.46003 Boehringer Ingelheim Investigational Site	Västerås		Sweden
50	1160.42.46004 Boehringer Ingelheim Investigational Site	Örebro		Sweden

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00157248

Other Study ID Numbers:

1160.42

First Posted:

Sep 12, 2005

Last Update Posted:

May 19, 2014

Last Verified:

Feb 1, 2014

Additional relevant MeSH terms:

Atrial Fibrillation

Dabigatran

Study Results

Participant Flow

Recruitment Details	This was a non-randomized open-label extension study of study 1160.20. Patients initially continued Dabigatran treatment of 1160.20; per protocol amendment, most patients moved to 150 mg bid. All events were assigned to the Dabigatran regimen that a patient received prior to the event and patients may be counted in multiple regimens
Pre-assignment Detail	In this non-randomized follow-up study, events are displayed cumulatively that occurred in the initial study (1160.20) or in the present study.

Arm/Group Title	Dabigatran Etexilate, 150 mg QD (Once Daily)	Dabigatran Etexilate, 150 mg BID (Twice Daily)	Dabigatran Etexilate, 300 mg QD (Once Daily)	Dabigatran Etexilate, 300 mg BID (Twice Daily)
Arm/Group Description	Dosage used at study start	Dosage used at study start	Dosage used at study start	Dosage used at study start
Period Title: Overall Study
STARTED	98	89	50	124
COMPLETED	50	52	29	77
NOT COMPLETED	48	37	21	47

Baseline Characteristics

Arm/Group Title	Dabigatran Etexilate, 150 mg QD (Once Daily)	Dabigatran Etexilate, 150 mg BID (Twice Daily)	Dabigatran Etexilate, 300 mg QD (Once Daily)	Dabigatran Etexilate, 300 mg BID (Twice Daily)	Total
Arm/Group Description	Dosage used at study start	Dosage used at study start	Dosage used at study start	Dosage used at study start	Total of all reporting groups
Overall Participants	98	89	50	124	361
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	70.4 (8.6)	69.3 (8.2)	71.0 (6.8)	68.8 (8.5)	69.7 (8.2)
Sex: Female, Male (Count of Participants)
Female	19 19.4%	18 20.2%	10 20%	12 9.7%	59 16.3%
Male	79 80.6%	71 79.8%	40 80%	112 90.3%	302 83.7%
Atrial fibrillation (Number) [Number]
Persistent	40 (139) 40.8%	38 (40) 42.7%	15 (38) 30%	46 (15) 37.1%	139 38.5%
Permanent	40 40.8%	28 31.5%	25 50%	47 37.9%	140 38.8%
Paroxysmal	18 18.4%	23 25.8%	10 20%	31 25%	82 22.7%

Outcome Measures

1. Primary Outcome

Title	Yearly Event Rate for Composite Endpoint of Stroke, Transient Ischaemic Attacks, System Thromboembolism, Myocardial Infarction, Other Major Adverse Cardiac Events and Mortality.
Description	Time to first occurrence of stroke, transient ischaemic attacks, system thromboembolism, myocardial infarction, other major adverse cardiac events and mortality. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients. In this non-randomized follow-up study, most patients changed treatment regimens per amendment during conduct and treatment exposure was not comparable between regimens. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens. No statistical analysis was done.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Number [yearly event rate (percentage)]	0.0	17.0	5.0	5.7	4.5	2.4

2. Secondary Outcome

Title	Yearly Event Rate for Stroke
Description	Time to first occurrence of any fatal or non-fatal stroke. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients. In this non-randomized follow-up study, most patients changed treatment regimens per amendment during conduct and treatment exposure was not comparable between regimens. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens. No statistical analysis was done.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Number [yearly event rate (percentage)]	0.0	4.3	5.0	1.1	1.7	0.0

3. Secondary Outcome

Title	Yearly Event Rate of Ischaemic Stroke
Description	Time to first occurrence of any ischaemic stroke. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients. In this non-randomized follow-up study, most patients changed treatment regimens per amendment during conduct and treatment exposure was not comparable between regimens. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens. No statistical analysis was done.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Number [yearly event rate (percentage)]	0.0	4.3	5.0	0.5	1.7	0.0

4. Secondary Outcome

Title	Yearly Event Rate of Haemorrhagic Stroke
Description	Time to first occurrence of any haemorrhagic stroke. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients. In this non-randomized follow-up study, most patients changed treatment regimens per amendment during conduct and treatment exposure was not comparable between regimens. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens. No statistical analysis was done.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Number [yearly event rate (percentage)]	0.0	0.0	0.0	0.6	0.0	0.0

5. Secondary Outcome

Title	Yearly Event Rate for Transient Ischaemic Attacks
Description	Time to first occurrence of any transient ischaemic attacks. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients. In this non-randomized follow-up study, most patients changed treatment regimens per amendment during conduct and treatment exposure was not comparable between regimens. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens. No statistical analysis was done.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Number [yearly event rate (percentage)]	0.0	0.0	0.0	0.2	0.4	0.0

6. Secondary Outcome

Title	Yearly Event Rate for Systemic Thromboembolism
Description	Time to first occurrence of any non-central nervous system systemic thromboembolism. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients. In this non-randomized follow-up study, most patients changed treatment regimens per amendment during conduct and treatment exposure was not comparable between regimens. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens. No statistical analysis was done.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Number [yearly event rate (percentage)]	0.0	8.5	0.0	0.2	0.4	1.2

7. Secondary Outcome

Title	Yearly Event Rate of Myocardial Infarction
Description	Time to first occurrence of any myocardial infarction. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients. In this non-randomized follow-up study, most patients changed treatment regimens per amendment during conduct and treatment exposure was not comparable between regimens. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens. No statistical analysis was done.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Number [yearly event rate (percentage)]	0.0	0.0	0.0	1.1	0.4	0.0

8. Secondary Outcome

Title	Yearly Event Rate of Other Major Adverse Cardiac Events
Description	Time to first occurrence of any other major adverse cardiac events. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients. In this non-randomized follow-up study, most patients changed treatment regimens per amendment during conduct and treatment exposure was not comparable between regimens. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens. No statistical analysis was done.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Number [yearly event rate (percentage)]	0.0	8.5	0.0	1.1	0.8	1.2

9. Secondary Outcome

Title	Yearly Event Rate of Death
Description	Time to death of any cause. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients. In this non-randomized follow-up study, most patients changed treatment regimens per amendment during conduct and treatment exposure was not comparable between regimens. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens. No statistical analysis was done.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Number [yearly event rate (percentage)]	0.0	0.0	0.0	2.7	2.1	0.0

10. Primary Outcome

Title	Yearly Event Rate for Major Bleeding
Description	Time to first occurrence of fatal or life-threatening, retroperitoneal, intracranial, intraocular, or intraspinal bleeding, which required surgical treatment, led to a transfusion of a minimum of 2 units of packed cells or whole blood, or led to a fall in hemoglobin of 20g/L or less. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients. In this non-randomized follow-up study, most patients changed treatment regimens per amendment during conduct and treatment exposure was not comparable between regimens. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens. No statistical analysis was done.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Number [yearly event rate (percentage)]	0.0	0.0	6.6	3.1	0.8	7.3

11. Primary Outcome

Title	Yearly Event Rate for Major + Minor/Relevant Bleeding
Description	Time to first occurrence of either major or minor/relevant bleeding. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients. In this non-randomized follow-up study, most patients changed treatment regimens per amendment during conduct and treatment exposure was not comparable between regimens. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens. No statistical analysis was done.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Number [yearly event rate (percentage)]	0.0	8.5	11.6	7.6	6.6	26.8

12. Primary Outcome

Title	Yearly Event Rate for Any Bleeding
Description	Time to first occurrence of any bleeding event. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients. In this non-randomized follow-up study, most patients changed treatment regimens per amendment during conduct and treatment exposure was not comparable between regimens. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens. No statistical analysis was done.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Number [yearly event rate (percentage)]	0.0	25.5	21.5	14.7	14.9	58.5

13. Secondary Outcome

Title	Yearly Event Rate for Composite Secondary Endpoint of Ischaemic Stroke, Transient Ischaemic Attacks, Non-central Nervous System Systemic Thromboembolism, Myocardial Infarction, Other Major Adverse Cardiac Events and All-cause Mortality
Description	Time to first occurrence of ischaemic stroke, transient ischaemic attacks, non-central nervous system systemic thromboembolism, myocardial infarction, other major adverse cardiac events and all-cause mortality. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients. In this non-randomized follow-up study, most patients changed treatment regimens per amendment during conduct and treatment exposure was not comparable between regimens. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens. No statistical analysis was done.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Number [yearly event rate (percentage)]	0.0	17.0	5.0	5.5	4.5	2.4

14. Secondary Outcome

Title	Severe Adverse Event
Description	Frequency of patients with severe adverse events.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Number [participants]	0 0%	5 5.6%	13 26%	96 77.4%	28 7.8%	16 NaN

15. Primary Outcome

Title	Yearly Event Rate for Minor Bleeding
Description	Time to first occurrence of minor bleeding. A minor bleeding event is any bleed that does not qualify as a major bleed. All minor bleeding events not fulfilling one of the criteria for clinically relevant were classified as nuisance bleeds. Clinically-relevant was defined as spontaneous skin hematoma ≥25 cm², spontaneous nose bleed >5 min, macroscopic hematuria spontaneous or lasting longer than 24 hours if associated with an intervention, spontaneous rectal bleeding, gingival bleeding >5 min, leading to hospitalization, leading to a transfusion of <2 units of packed cells or whole blood and any other bleeding event considered clinically relevant by the investigator. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients. In this non-randomized follow-up study, most patients changed treatment regimens per amendment during conduct and treatment exposure was not comparable between regimens. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens. No statistical analysis was done.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
Clinically relevant	0.0	8.5	5.0	4.5	5.8	19.5
Nuisance only	0.0	17.0	9.9	7.1	8.3	31.7

16. Secondary Outcome

Title	Laboratory Analyses
Description	Frequency of patients with possible clinically significant abnormalities, i.e. with values out of normal range. Normal ranges are defined as: Alanine aminotransferase (ALT): 5-45 [U/L] Aspartate aminotransferase (AST): 10-40 [U/L] Bilirubin, total: 0.2-1.0 [mg/dL]
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
All treated patients.

Arm/Group Title	50 mg Once Daily	50 mg Twice Daily	150 mg Once Daily	150 mg Twice Daily	300 mg Once Daily	300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily	Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
Measure Participants	1	105	102	356	90	161
AST > 3*ULN	0 0%	0 0%	0 0%	10 8.1%	3 0.8%	1 NaN
ALT > 3*ULN	0 0%	0 0%	0 0%	9 7.3%	4 1.1%	2 NaN
Bilirubin > 2*ULN	0 0%	0 0%	0 0%	5 4%	2 0.6%	0 NaN

Adverse Events

	50 mg Once Daily		50 mg Twice Daily		150 mg Once Daily		150 mg Twice Daily		300 mg Once Daily		300 mg Twice Daily
Time Frame	5 years
Adverse Event Reporting Description	All treated patients. In this follow-up study, events are displayed cumulatively that occurred in the initial study (1160.20) or in the present study. Most patients changed treatment regimens per amendment during conduct. Events were assigned to the regimen a patient received prior to the event, and patients may be counted in multiple regimens.

Arm/Group Title	50 mg Once Daily		50 mg Twice Daily		150 mg Once Daily		150 mg Twice Daily		300 mg Once Daily		300 mg Twice Daily
Arm/Group Description	Number of Participants treated at any time with 50 mg of Dabigatran etexilate once daily		Number of Participants treated at any time with 50 mg of Dabigatran etexilate twice daily		Number of Participants treated at any time with 150 mg of Dabigatran etexilate once daily		Number of Participants treated at any time with 150 mg of Dabigatran etexilate twice daily		Number of Participants treated at any time with 300 mg of Dabigatran etexilate once daily		Number of Participants treated at any time with 300 mg of Dabigatran etexilate twice daily
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	50 mg Once Daily		50 mg Twice Daily		150 mg Once Daily		150 mg Twice Daily		300 mg Once Daily		300 mg Twice Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		8/105 (7.6%)		20/102 (19.6%)		153/356 (43%)		39/90 (43.3%)		21/161 (13%)
Blood and lymphatic system disorders
Anaemia	0/1 (0%)		0/105 (0%)		1/102 (1%)		9/356 (2.5%)		1/90 (1.1%)		0/161 (0%)
Cardiac disorders
Acute coronary syndrome	0/1 (0%)		1/105 (1%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		1/161 (0.6%)
Acute myocardial infarction	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		0/90 (0%)		0/161 (0%)
Angina pectoris	0/1 (0%)		0/105 (0%)		1/102 (1%)		5/356 (1.4%)		1/90 (1.1%)		0/161 (0%)
Angina unstable	0/1 (0%)		0/105 (0%)		0/102 (0%)		6/356 (1.7%)		0/90 (0%)		1/161 (0.6%)
Aortic valve stenosis	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		0/90 (0%)		0/161 (0%)
Arrhythmia	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Atrial conduction time prolongation	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Atrial fibrillation	0/1 (0%)		0/105 (0%)		0/102 (0%)		12/356 (3.4%)		3/90 (3.3%)		2/161 (1.2%)
Atrial flutter	0/1 (0%)		0/105 (0%)		1/102 (1%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Atrial thrombosis	0/1 (0%)		1/105 (1%)		0/102 (0%)		0/356 (0%)		0/90 (0%)		0/161 (0%)
Atrioventricular block complete	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Bradycardia	0/1 (0%)		0/105 (0%)		1/102 (1%)		6/356 (1.7%)		0/90 (0%)		2/161 (1.2%)
Cardiac arrest	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		1/90 (1.1%)		0/161 (0%)
Cardiac asthma	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Cardiac failure	0/1 (0%)		0/105 (0%)		2/102 (2%)		14/356 (3.9%)		7/90 (7.8%)		0/161 (0%)
Cardiac failure congestive	0/1 (0%)		0/105 (0%)		2/102 (2%)		3/356 (0.8%)		3/90 (3.3%)		0/161 (0%)
Cardio-respiratory arrest	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Cardiogenic shock	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		0/161 (0%)
Conduction disorder	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Cor pulmonale	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Coronary artery disease	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Coronary artery stenosis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		0/161 (0%)
Mitral valve incompetence	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Myocardial infarction	0/1 (0%)		0/105 (0%)		0/102 (0%)		7/356 (2%)		1/90 (1.1%)		0/161 (0%)
Myocardial ischaemia	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		0/90 (0%)		0/161 (0%)
Palpitations	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Pericardial effusion	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Sick sinus syndrome	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		1/90 (1.1%)		0/161 (0%)
Tachycardia	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		0/161 (0%)
Ventricular arrhythmia	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		0/161 (0%)
Ventricular fibrillation	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		0/90 (0%)		0/161 (0%)
Ventricular tachycardia	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		1/90 (1.1%)		0/161 (0%)
Ear and labyrinth disorders
Vertigo	0/1 (0%)		0/105 (0%)		0/102 (0%)		4/356 (1.1%)		0/90 (0%)		0/161 (0%)
Eye disorders
Cataract	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Retinal detachment	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Retinal haemorrhage	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		0/90 (0%)		1/161 (0.6%)
Gastrointestinal disorders
Abdominal adhesions	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Abdominal discomfort	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Abdominal pain	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Abdominal pain upper	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		1/90 (1.1%)		0/161 (0%)
Ascites	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Crohn's disease	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		0/90 (0%)		1/161 (0.6%)
Diarrhoea	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Diverticulum	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Diverticulum intestinal	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Duodenal ulcer haemorrhage	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Dyspepsia	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Dysphagia	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Faeces discoloured	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Gastric haemorrhage	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Gastric ulcer	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		0/90 (0%)		1/161 (0.6%)
Gastrointestinal haemorrhage	0/1 (0%)		0/105 (0%)		1/102 (1%)		2/356 (0.6%)		1/90 (1.1%)		2/161 (1.2%)
Gastrooesophageal reflux disease	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		0/90 (0%)		1/161 (0.6%)
Ileus	0/1 (0%)		1/105 (1%)		0/102 (0%)		0/356 (0%)		0/90 (0%)		0/161 (0%)
Inguinal hernia	0/1 (0%)		0/105 (0%)		1/102 (1%)		7/356 (2%)		0/90 (0%)		0/161 (0%)
Intestinal ischaemia	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Intestinal obstruction	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		0/161 (0%)
Large intestinal obstruction	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Lower gastrointestinal haemorrhage	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		0/90 (0%)		1/161 (0.6%)
Melaena	0/1 (0%)		0/105 (0%)		0/102 (0%)		4/356 (1.1%)		0/90 (0%)		0/161 (0%)
Nausea	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Oesophageal ulcer	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		1/161 (0.6%)
Oesophagitis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Pancreatic pseudocyst	0/1 (0%)		0/105 (0%)		1/102 (1%)		0/356 (0%)		0/90 (0%)		0/161 (0%)
Pancreatitis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Pancreatitis acute	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Peritonitis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Rectal haemorrhage	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		1/161 (0.6%)
Small intestinal obstruction	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Vomiting	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
General disorders
Asthenia	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Chest discomfort	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		0/90 (0%)		0/161 (0%)
Chest pain	0/1 (0%)		0/105 (0%)		1/102 (1%)		14/356 (3.9%)		1/90 (1.1%)		2/161 (1.2%)
Drug ineffective	0/1 (0%)		0/105 (0%)		1/102 (1%)		0/356 (0%)		0/90 (0%)		0/161 (0%)
Dysplasia	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Fatigue	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		0/161 (0%)
General physical health deterioration	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Impaired healing	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Influenza like illness	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Malaise	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Oedema peripheral	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		1/90 (1.1%)		0/161 (0%)
Pyrexia	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		1/90 (1.1%)		0/161 (0%)
Sudden cardiac death	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Sudden death	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		0/90 (0%)		0/161 (0%)
Hepatobiliary disorders
Bile duct stone	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Cholecystitis	0/1 (0%)		1/105 (1%)		0/102 (0%)		3/356 (0.8%)		0/90 (0%)		0/161 (0%)
Cholecystitis acute	0/1 (0%)		0/105 (0%)		1/102 (1%)		0/356 (0%)		0/90 (0%)		0/161 (0%)
Cholelithiasis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		2/90 (2.2%)		0/161 (0%)
Hepatic function abnormal	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Immune system disorders
Drug hypersensitivity	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Infections and infestations
Appendicitis perforated	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Arthritis bacterial	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Bronchitis	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		0/90 (0%)		0/161 (0%)
Cellulitis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Diverticulitis	0/1 (0%)		1/105 (1%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		1/161 (0.6%)
Endocarditis	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Erysipelas	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		0/90 (0%)		0/161 (0%)
Gangrene	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Gastroenteritis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		0/161 (0%)
Implant site infection	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Infected skin ulcer	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Infective exacerbation of chronic obstructive airways disease	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		0/161 (0%)
Lobar pneumonia	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Localised infection	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Meningitis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Nail infection	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Pneumonia	0/1 (0%)		0/105 (0%)		1/102 (1%)		15/356 (4.2%)		2/90 (2.2%)		1/161 (0.6%)
Post procedural infection	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Sepsis	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Sinusitis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Skin infection	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Urinary tract infection	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Urosepsis	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		1/90 (1.1%)		0/161 (0%)
Wound infection	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Injury, poisoning and procedural complications
Ankle fracture	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Chest injury	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Fall	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		1/90 (1.1%)		0/161 (0%)
Femur fracture	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Gastrointestinal stoma complication	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Hip fracture	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		0/90 (0%)		0/161 (0%)
Implantable defibrillator malfunction	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Incisional hernia	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Postoperative ileus	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Radius fracture	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		0/90 (0%)		0/161 (0%)
Rib fracture	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		0/161 (0%)
Skin laceration	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Stent-graft endoleak	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Subdural haematoma	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Tendon rupture	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Upper limb fracture	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Wrist fracture	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Investigations
Alanine aminotransferase increased	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Blood creatinine increased	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Blood pressure systolic inspiratory decreased	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Electrocardiogram ST segment depression	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Haemoglobin decreased	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Heart rate increased	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Heart rate irregular	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Hepatic enzyme increased	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Liver function test abnormal	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Metabolism and nutrition disorders
Dehydration	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		1/90 (1.1%)		0/161 (0%)
Diabetes mellitus	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Gout	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Hyperglycaemia	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Hyperkalaemia	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Hypoglycaemia	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		0/90 (0%)		0/161 (0%)
Hypokalaemia	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Hyponatraemia	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Back pain	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Gouty arthritis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Lumbar spinal stenosis	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		1/161 (0.6%)
Muscle spasms	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Neck pain	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Osteitis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		0/161 (0%)
Osteoarthritis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Osteoporosis	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Pain in extremity	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/1 (0%)		0/105 (0%)		0/102 (0%)		4/356 (1.1%)		0/90 (0%)		0/161 (0%)
Bladder cancer	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Bladder cancer recurrent	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Bladder papilloma	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		2/90 (2.2%)		0/161 (0%)
Bladder transitional cell carcinoma	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Bronchial carcinoma	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Chronic lymphocytic leukaemia	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Colon cancer	0/1 (0%)		0/105 (0%)		1/102 (1%)		2/356 (0.6%)		0/90 (0%)		1/161 (0.6%)
Colon cancer metastatic	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Lipoma	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Lung cancer metastatic	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Lung neoplasm malignant	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Lymphoma	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Malignant melanoma	0/1 (0%)		0/105 (0%)		1/102 (1%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Metastases to bone	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Metastases to lymph nodes	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Multiple myeloma	0/1 (0%)		0/105 (0%)		1/102 (1%)		0/356 (0%)		0/90 (0%)		0/161 (0%)
Neoplasm skin	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Non-Hodgkin's lymphoma	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Oesophageal carcinoma	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Ovarian cancer	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Prostate cancer	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Renal cancer	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Renal cell carcinoma	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Squamous cell carcinoma of skin	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Transitional cell carcinoma	0/1 (0%)		0/105 (0%)		1/102 (1%)		0/356 (0%)		0/90 (0%)		0/161 (0%)
Nervous system disorders
Cerebral haemorrhage	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		0/90 (0%)		0/161 (0%)
Cerebral infarction	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Cerebrovascular accident	0/1 (0%)		1/105 (1%)		1/102 (1%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Dizziness	0/1 (0%)		0/105 (0%)		0/102 (0%)		6/356 (1.7%)		2/90 (2.2%)		0/161 (0%)
Encephalopathy	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Epilepsy	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		0/90 (0%)		1/161 (0.6%)
Haemorrhage intracranial	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Haemorrhagic stroke	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Hemiparesis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Ischaemic cerebral infarction	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Ischaemic stroke	0/1 (0%)		0/105 (0%)		3/102 (2.9%)		2/356 (0.6%)		2/90 (2.2%)		0/161 (0%)
Loss of consciousness	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Memory impairment	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Migraine	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Myasthenic syndrome	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Paraesthesia	0/1 (0%)		1/105 (1%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Syncope	0/1 (0%)		0/105 (0%)		1/102 (1%)		7/356 (2%)		3/90 (3.3%)		1/161 (0.6%)
Transient ischaemic attack	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		1/90 (1.1%)		0/161 (0%)
Psychiatric disorders
Anxiety	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Confusional state	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Delirium	0/1 (0%)		0/105 (0%)		1/102 (1%)		0/356 (0%)		0/90 (0%)		0/161 (0%)
Renal and urinary disorders
Albuminuria	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Calculus urethral	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Haematuria	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Hydronephrosis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Renal cyst	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Renal failure acute	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		0/90 (0%)		0/161 (0%)
Renal failure chronic	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Renal impairment	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Renal infarct	0/1 (0%)		1/105 (1%)		0/102 (0%)		0/356 (0%)		0/90 (0%)		0/161 (0%)
Urethral haemorrhage	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Urinary retention	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		0/90 (0%)		0/161 (0%)
Urinary tract disorder	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/1 (0%)		0/105 (0%)		1/102 (1%)		5/356 (1.4%)		1/90 (1.1%)		0/161 (0%)
Cystocele	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Prostatism	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		0/161 (0%)
Rectocele	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Uterine prolapse	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/1 (0%)		0/105 (0%)		0/102 (0%)		5/356 (1.4%)		0/90 (0%)		0/161 (0%)
Dyspnoea	0/1 (0%)		0/105 (0%)		0/102 (0%)		9/356 (2.5%)		4/90 (4.4%)		1/161 (0.6%)
Epistaxis	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		1/161 (0.6%)
Haemoptysis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Haemothorax	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Lung infiltration	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Pleural effusion	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Pneumothorax	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Pulmonary fibrosis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Pulmonary oedema	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		0/161 (0%)
Respiratory distress	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Respiratory failure	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		0/161 (0%)
Restrictive pulmonary disease	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Skin and subcutaneous tissue disorders
Skin discolouration	0/1 (0%)		1/105 (1%)		0/102 (0%)		0/356 (0%)		0/90 (0%)		0/161 (0%)
Skin ulcer	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Social circumstances
Joint prosthesis user	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Surgical and medical procedures
Cardiac pacemaker replacement	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Hip arthroplasty	0/1 (0%)		1/105 (1%)		0/102 (0%)		0/356 (0%)		0/90 (0%)		0/161 (0%)
Vascular disorders
Aneurysm	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Aortic aneurysm	0/1 (0%)		0/105 (0%)		1/102 (1%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Aortic aneurysm rupture	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Aortic dissection	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		1/90 (1.1%)		0/161 (0%)
Aortic stenosis	0/1 (0%)		0/105 (0%)		0/102 (0%)		2/356 (0.6%)		0/90 (0%)		0/161 (0%)
Circulatory collapse	0/1 (0%)		1/105 (1%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Deep vein thrombosis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Femoral artery aneurysm	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Femoral artery occlusion	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Haemorrhage	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Hypertension	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Hypotension	0/1 (0%)		0/105 (0%)		0/102 (0%)		4/356 (1.1%)		1/90 (1.1%)		0/161 (0%)
Intermittent claudication	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Ischaemia	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Peripheral arterial occlusive disease	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Peripheral embolism	0/1 (0%)		1/105 (1%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Peripheral ischaemia	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Peripheral vascular disorder	0/1 (0%)		0/105 (0%)		1/102 (1%)		0/356 (0%)		0/90 (0%)		0/161 (0%)
Temporal arteritis	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Vasculitis	0/1 (0%)		0/105 (0%)		0/102 (0%)		1/356 (0.3%)		0/90 (0%)		0/161 (0%)
Wound haemorrhage	0/1 (0%)		0/105 (0%)		0/102 (0%)		0/356 (0%)		1/90 (1.1%)		0/161 (0%)
Other (Not Including Serious) Adverse Events
	50 mg Once Daily		50 mg Twice Daily		150 mg Once Daily		150 mg Twice Daily		300 mg Once Daily		300 mg Twice Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		18/105 (17.1%)		17/102 (16.7%)		219/356 (61.5%)		65/90 (72.2%)		57/161 (35.4%)
Blood and lymphatic system disorders
Anaemia	0/1 (0%)		0/105 (0%)		0/102 (0%)		21/356 (5.9%)		3/90 (3.3%)		2/161 (1.2%)
Cardiac disorders
Angina pectoris	0/1 (0%)		1/105 (1%)		1/102 (1%)		20/356 (5.6%)		8/90 (8.9%)		4/161 (2.5%)
Eye disorders
Cataract	0/1 (0%)		0/105 (0%)		0/102 (0%)		19/356 (5.3%)		3/90 (3.3%)		0/161 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/1 (0%)		2/105 (1.9%)		1/102 (1%)		19/356 (5.3%)		1/90 (1.1%)		4/161 (2.5%)
Constipation	0/1 (0%)		7/105 (6.7%)		2/102 (2%)		14/356 (3.9%)		9/90 (10%)		1/161 (0.6%)
Diarrhoea	0/1 (0%)		9/105 (8.6%)		4/102 (3.9%)		19/356 (5.3%)		4/90 (4.4%)		6/161 (3.7%)
Dyspepsia	0/1 (0%)		3/105 (2.9%)		2/102 (2%)		22/356 (6.2%)		3/90 (3.3%)		11/161 (6.8%)
Nausea	0/1 (0%)		3/105 (2.9%)		2/102 (2%)		22/356 (6.2%)		10/90 (11.1%)		6/161 (3.7%)
General disorders
Chest pain	0/1 (0%)		2/105 (1.9%)		1/102 (1%)		18/356 (5.1%)		5/90 (5.6%)		8/161 (5%)
Fatigue	0/1 (0%)		2/105 (1.9%)		4/102 (3.9%)		39/356 (11%)		12/90 (13.3%)		10/161 (6.2%)
Oedema peripheral	0/1 (0%)		3/105 (2.9%)		6/102 (5.9%)		46/356 (12.9%)		10/90 (11.1%)		8/161 (5%)
Infections and infestations
Bronchitis	0/1 (0%)		1/105 (1%)		2/102 (2%)		17/356 (4.8%)		5/90 (5.6%)		3/161 (1.9%)
Influenza	0/1 (0%)		1/105 (1%)		1/102 (1%)		22/356 (6.2%)		9/90 (10%)		11/161 (6.8%)
Nasopharyngitis	0/1 (0%)		3/105 (2.9%)		5/102 (4.9%)		43/356 (12.1%)		13/90 (14.4%)		7/161 (4.3%)
Pneumonia	0/1 (0%)		0/105 (0%)		2/102 (2%)		20/356 (5.6%)		3/90 (3.3%)		1/161 (0.6%)
Urinary tract infection	0/1 (0%)		2/105 (1.9%)		1/102 (1%)		23/356 (6.5%)		3/90 (3.3%)		2/161 (1.2%)
Injury, poisoning and procedural complications
Contusion	0/1 (0%)		0/105 (0%)		2/102 (2%)		19/356 (5.3%)		3/90 (3.3%)		11/161 (6.8%)
Fall	0/1 (0%)		1/105 (1%)		0/102 (0%)		17/356 (4.8%)		6/90 (6.7%)		1/161 (0.6%)
Wound	0/1 (0%)		1/105 (1%)		0/102 (0%)		5/356 (1.4%)		6/90 (6.7%)		1/161 (0.6%)
Metabolism and nutrition disorders
Diabetes mellitus	0/1 (0%)		3/105 (2.9%)		2/102 (2%)		12/356 (3.4%)		5/90 (5.6%)		6/161 (3.7%)
Gout	0/1 (0%)		0/105 (0%)		3/102 (2.9%)		12/356 (3.4%)		6/90 (6.7%)		0/161 (0%)
Hypercholesterolaemia	0/1 (0%)		1/105 (1%)		0/102 (0%)		6/356 (1.7%)		6/90 (6.7%)		3/161 (1.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/1 (0%)		2/105 (1.9%)		3/102 (2.9%)		23/356 (6.5%)		6/90 (6.7%)		4/161 (2.5%)
Back pain	0/1 (0%)		2/105 (1.9%)		7/102 (6.9%)		28/356 (7.9%)		13/90 (14.4%)		3/161 (1.9%)
Muscle spasms	0/1 (0%)		1/105 (1%)		0/102 (0%)		11/356 (3.1%)		5/90 (5.6%)		2/161 (1.2%)
Myalgia	0/1 (0%)		0/105 (0%)		1/102 (1%)		5/356 (1.4%)		6/90 (6.7%)		2/161 (1.2%)
Pain in extremity	0/1 (0%)		4/105 (3.8%)		4/102 (3.9%)		18/356 (5.1%)		7/90 (7.8%)		2/161 (1.2%)
Nervous system disorders
Dizziness	0/1 (0%)		7/105 (6.7%)		4/102 (3.9%)		36/356 (10.1%)		13/90 (14.4%)		14/161 (8.7%)
Headache	0/1 (0%)		6/105 (5.7%)		3/102 (2.9%)		22/356 (6.2%)		7/90 (7.8%)		5/161 (3.1%)
Psychiatric disorders
Insomnia	0/1 (0%)		1/105 (1%)		1/102 (1%)		18/356 (5.1%)		3/90 (3.3%)		2/161 (1.2%)
Renal and urinary disorders
Haematuria	0/1 (0%)		1/105 (1%)		2/102 (2%)		32/356 (9%)		4/90 (4.4%)		4/161 (2.5%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/1 (0%)		0/105 (0%)		1/102 (1%)		6/356 (1.7%)		6/90 (6.7%)		2/161 (1.2%)
Cough	0/1 (0%)		1/105 (1%)		5/102 (4.9%)		29/356 (8.1%)		15/90 (16.7%)		9/161 (5.6%)
Dyspnoea	0/1 (0%)		1/105 (1%)		6/102 (5.9%)		37/356 (10.4%)		12/90 (13.3%)		9/161 (5.6%)
Epistaxis	0/1 (0%)		0/105 (0%)		3/102 (2.9%)		23/356 (6.5%)		10/90 (11.1%)		11/161 (6.8%)
Skin and subcutaneous tissue disorders
Rash	0/1 (0%)		0/105 (0%)		1/102 (1%)		12/356 (3.4%)		8/90 (8.9%)		3/161 (1.9%)
Vascular disorders
Haematoma	0/1 (0%)		1/105 (1%)		1/102 (1%)		17/356 (4.8%)		10/90 (11.1%)		6/161 (3.7%)
Hypertension	0/1 (0%)		2/105 (1.9%)		5/102 (4.9%)		32/356 (9%)		14/90 (15.6%)		5/161 (3.1%)
Varicose vein	0/1 (0%)		0/105 (0%)		0/102 (0%)		3/356 (0.8%)		5/90 (5.6%)		0/161 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract

Results Point of Contact

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

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00157248

Other Study ID Numbers:

1160.42

First Posted:

Sep 12, 2005

Last Update Posted:

May 19, 2014

Last Verified:

Feb 1, 2014

Long-term, Open-label Follow-up Treatment of Patients With A-fib Who Have Been Previously Treated With BIBR 1048

Study Details

Study Description

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Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

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Exclusion Criteria:

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Investigators

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Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

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