PETRO Stroke Prevention in Patients With AF by Treatment With Dabigatran, With and Without Aspirin, Compared to Warfarin

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01227629
• Collaborator: (none)
• Enrollment: 502
• Locations: 38
• Arms: 10
• Patients Per Site: 13.2

Study Details

Study Description

Brief Summary

The purpose of this trial is to evaluate the safety of different doses of BIBR 1048, alone or in combination with acetylsalicylic acid (ASA), as determined by the rates of bleeding and other adverse events.

A secondary objective of this trial is to evaluate the anticoagulant effect of different doses of BIBR 1048, based on the reduction of plasma concentrations of D-dimer, a laboratory marker for activated coagulation in patients with atrial fibrillation (AF), and to correlate bleeding and other events with pharmacokinetic (PK) and pharmacodynamic (PD) data.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Drug: dabigatran with ASA; Drug: dabigatran with ASA; Drug: dabigatran with ASA; Drug: dabigatran with ASA; Drug: dabigatran with ASA; Drug: dabigatran with ASA; Drug: warfarin; Drug: dabigatran without ASA; Drug: dabigatran without ASA; Drug: dabigatran without ASA	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 502 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Primary Purpose: Prevention
• Official Title: Dose Exploration in Patients With Atrial Fibrillation
• Study Start Date: Sep 1, 2003
• Actual Primary Completion Date: Nov 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: dabigatran 50 mg twice daily (bid) Dabigatran: one capsule in the morning and 1 capsule in the evening. Twice daily (bis in die = bid).	Drug: dabigatran without ASA; dose comparison
Experimental: dabigatran 50 mg bid + 81 mg ASA qd Dabigatran: one capsule in the morning and 1 capsule in the evening. Acetylsalicylic acid (ASA) once daily (quaque dies = qd) in the morning.	Drug: dabigatran with ASA; dose comparison in combination
Experimental: dabigatran 50 mg bid + 325 mg ASA qd Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning	Drug: dabigatran with ASA; dose comparison in combination
Experimental: dabigatran 150 mg bid Dabigatran: one capsule in the morning and 1 capsule in the evening	Drug: dabigatran without ASA; dose comparison
Experimental: dabigatran 150 mg bid + 81 mg ASA qd Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning	Drug: dabigatran with ASA; dose comparison in combination
Experimental: dabigatran 150 mg bid + 325 mg ASA qd Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning	Drug: dabigatran with ASA; dose comparison in combination
Experimental: dabigatran 300 mg bid Dabigatran: one capsule in the morning and 1 capsule in the evening	Drug: dabigatran without ASA; dose comparison
Experimental: dabigatran 300 mg bid + 81 mg ASA qd Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning	Drug: dabigatran with ASA; dose comparison in combination
Experimental: dabigatran 300 mg bid + 325 mg ASA qd Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning	Drug: dabigatran with ASA; dose comparison in combination
Active Comparator: warfarin once daily, dosed to target International Normalised Ratio (INR) 2.0 to 3.0	Drug: warfarin; comparator

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Fatal or Life-threatening Major Bleeding Events [12 weeks]

   Retroperitoneal, intracranial, intraocular, or intraspinal bleeding, or requiring surgical treatment, or leading to a transfusion of 2 units or more, or leading to a fall in hemoglobin of 20g/L or more

2. Number of Participants With Minor/Relevant Bleeding Events [12 weeks]

   Haematuria, rectal bleeding, gingival bleeding, skin hematoma of 25cm^2 or more, nose bleed of more than 5 minutes duration, bleeding leading to a hospitalization, leading to a transfusion of less than 2 units or any other clinically relevant bleeding

3. Number of Participants With Minor/Nuisance Bleeding Events [12 weeks]

   All bleeding events not fulfilling one of the criteria for major bleeding event or minor/relevant bleeding events.

Secondary Outcome Measures

1. Number of Participants With Thromboembolic Events: Composite Endpoint [12 weeks]

   Combination of ischemic stroke (fatal or non fatal), transient ischemic attack, systemic thromboembolism, myocardial infarction (fatal or non fatal), other major adverse cardiac event and all cause mortality

2. Number of Participants With Thromboembolic Events: Ischemic Stroke [12 weeks]

   Occurence of an ischemic stroke (fatal or non-fatal)

3. Thromboembolic Events: Number of Participants With Transient Ischemic Attack [12 weeks]

   Occurence of a transient ischemic attack

4. Thromboembolic Events: Number of Participants With Systemic Thromboembolism [12 weeks]

   Occurence of a systemic thromboembolism

5. Thromboembolic Events: Number of Participants With Myocardial Infarction [12 weeks]

   Occurence of a myocardial infarction

6. Thromboembolic Events: Number of Participants With Other Major Cardiac Events [12 weeks]

   Occurence of other major adverse cardiac events

7. Thromboembolic Events: Number of Participants Who Died [12 weeks]

   Occurence of death by all causes

8. D-dimer: Difference From Baseline [baseline and 12 weeks]

   Difference in D-dimer from baseline to last available value

9. Soluble Fibrin: Difference From Baseline [baseline and 12 weeks]

   Difference from baseline to visit 7

10. 11-dehydrothromboxane B2 (TXB2): Difference From Baseline [baseline and 12 weeks]

    Difference from baseline to visit 7

11. Ecarin Clotting Time (ECT): Difference From Baseline [baseline and 12 weeks]

12. Activated Partial Thromboplastin Time (aPTT): Difference From Baseline [baseline and 12 weeks]

13. Trough Plasma Concentration of Dabigatran (BIBR 953) [12 weeks]

    The values of the trough plasma concentration of dabigatran (BIBR 953) are the by-patient geometric means of week 1, 4 and 12.

14. Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline [12 weeks]

    Increase of AST to more than two times the baseline value

15. Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline [12 weeks]

    Increase of AP to more than two times the baseline value

16. Number of Participants With Increase of Bilirubin to >2*Baseline [12 weeks]

    Increase of Bilirubin to more than two times the baseline value

17. Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline [12 weeks]

    Number of Participants with Increase of ALT to more than two times the baseline value

18. Severity of Adverse Events [12 weeks]

    Total number of patients with any adverse event of worst intensity 'mild', 'moderate' and 'severe'.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria

1. Non-rheumatic atrial fibrillation.

2. Coronary artery disease (CAD), documented by previous myocard infarction (MI), angina, positive stress test, previous coronary intervention or bypass surgery, or atherosclerotic lesion(s) diagnosed by coronary angiography) is only considered as one of several possible qualifying risk factors. After recruitment of ca. 30%, a protocol amendment 4 was issued so that CAD was only considered as one of several possible qualifying risk factors, 2. see (3 f) below.

3. An additional risk factor for stroke, i.e. one or more of the following conditions/events:

4. hypertension (defined as systolic bloodpressure (SBP) > 140 mmHg and/or diastolic bloodpressure (DBP) > 90 mm Hg) requiring antihypertensive medical treatment.

5. diabetes mellitus (type I and II).

6. symptomatic heart failure or left ventricular dysfunction (ejection fraction (EF) < 40%).

7. a previous ischemic stroke or transient ischemic attack.

8. age greater than 75 years.

9. history of coronary artery disease (by amendment 4)

10. Treatment with warfarin or other vitamin K dependent anticoagulants for at least 8 weeks prior to inclusion. International normalised ratio (INR) should be within therapeutic range (i.e. INR 2.0 - 3.0) at visit 1 otherwise the visit should be rescheduled.

11. Age > = 18 years at entry.

12. Written, informed consent.

Exclusion criteria

1. Valvular heart disease.

2. Planned cardioversion.

3. Recent (=< 1 month) myocardial infarction, stroke or transient ischemic attack (TIA), or patients who have received a coronary stent within the last 6 months.

4. Intolerance or contraindications to acetylsalicylic acid (ASA).

5. Any contraindication to anticoagulant therapy.

6. Major bleeding within the last 6 months (other than gastrointestinal (GI) hemorrhage).

7. Severe renal impairment (estimated glomerular filtration rate (GFR) =< 30 mL/min).

8. Uncontrolled hypertension (SBP > 180 mmHg and/or DBP > 100 mmHg).

9. Abnormal liver function as defined by aspartat-aminotransferase (AST), alanin-aminotransferase (ALT), serum bilirubin or alkaline phosphatase (AP) above the reference range, or history of liver disease.

10. Women who are pregnant or of childbearing potential who refuses to use a medically acceptable form of contraception throughout the study.

11. Patients who have received an investigational drug within the last 30 days.

12. Patients scheduled for major surgery or invasive procedures which may cause bleeding, or those who have had major surgery or percutaneous coronary intervention (PCI) within 6 weeks.

13. Patients considered unreliable by the investigator.

14. Another indication for anticoagulant treatment.

15. Patients suffering from anemia.

16. Patients suffering from thrombocytopenia.

17. Any other condition which, in the discretion of the investigator, would not allow safe participation in the study.

18. Concomitant treatment with antiplatelet agents other than ASA.

19. Recent malignancy or radiation therapy (=< 6 month).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1160.20.10010	Fayetteville	Arkansas	United States
2	1160.20.10003 La Mesa Cardiac	La Mesa	California	United States
3	1160.20.10006 The Ford Research Institute, PA	Pensacola	Florida	United States
4	1160.20.10004	Port Charlotte	Florida	United States
5	1160.20.10002	St. Petersburg	Florida	United States
6	1160.20.10015	Baltimore	Maryland	United States
7	1160.20.10008	Westminister	Maryland	United States
8	1160.20.10012	Pittsfield	Massachusetts	United States
9	1160.20.10007	Troy	Michigan	United States
10	1160.20.10014	Hawthorne	New York	United States
11	1160.20.10013	New Hyde Park	New York	United States
12	1160.20.10009	North Durham	North Carolina	United States
13	1160.20.10001	Philadelphia	Pennsylvania	United States
14	1160.20.10005	Germantown	Tennessee	United States
15	1160.20.45010	Aalborg		Denmark
16	1160.20.45005 Aarhus Sygehus	Aarhus C		Denmark
17	1160.20.45007 Medicinsk afdeling	Brædstrup		Denmark
18	1160.20.45011 Medicinsk afd.	Esbjerg		Denmark
19	1160.20.45012 Afdeling B3	Frederikssund		Denmark
20	1160.20.45003 Forskningscentret plan 3	Helsingør		Denmark
21	1160.20.45004 Herlev Hospital	Herlev		Denmark
22	1160.20.45009 Medicinsk amb. B8	Holbæk		Denmark
23	1160.20.45002 Kardiologisk afdeling	Hvidovre		Denmark
24	1160.20.45014 Hjertemedicinsk afd.	Køge		Denmark
25	1160.20.45001 Kardiologisk Laboratorium	Odense		Denmark
26	1160.20.45013 Kardiologisk afd.	Roskilde		Denmark
27	1160.20.45006 Medicinsk afdeling	Svendborg		Denmark
28	1160.20.46013 HIA, Mälarsjukhuset	Eskilstuna		Sweden
29	1160.20.46007 Falu Lasarett	Falun		Sweden
30	1160.20.46005 Ryhovs Länssjukhus	Jönköping		Sweden
31	1160.20.46010 Länssjukhuset Kalmar	Kalmar		Sweden
32	1160.20.46009 Universitetssjukhuset MAS	Malmö		Sweden
33	1160.20.46008 Vrinnevisjukhuset	Norrköping		Sweden
34	1160.20.46002 Södersjukhuset	Stockholm		Sweden
35	1160.20.46011 Arytmienheten, Med klin	Stockholm		Sweden
36	1160.20.46006 Norrlands Universitetssjukhus	Umeå		Sweden
37	1160.20.46003 Centrallasarettet	Västerås		Sweden
38	1160.20.46004 Universitetssjukhuset	Örebro		Sweden

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01227629
• Other Study ID Numbers: 1160.20; PETRO trial
• First Posted: Oct 25, 2010
• Last Update Posted: May 5, 2014
• Last Verified: Apr 1, 2014

• Additional relevant MeSH terms: Atrial Fibrillation; Warfarin; Dabigatran

Study Results

Participant Flow

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Period Title: Overall Study
STARTED	58	20	27	99	34	33	98	33	30	70
COMPLETED	56	18	26	91	32	32	90	27	24	68
NOT COMPLETED	2	2	1	8	2	1	8	6	6	2

Baseline Characteristics

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0	Total
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral	Total of all reporting groups
Overall Participants	58	20	27	99	34	33	98	33	30	70	502
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	69.0 (8.8)	70.1 (9.4)	71.6 (8.1)	69.7 (7.7)	72.1 (9.0)	69.7 (8.0)	69.0 (9.1)	71.8 (7.2)	68.6 (7.1)	69.0 (8.3)	69.7 (8.3)
Sex: Female, Male (Count of Participants)
Female	12 20.7%	4 20%	5 18.5%	15 15.2%	8 23.5%	8 24.2%	19 19.4%	7 21.2%	2 6.7%	11 15.7%	91 18.1%
Male	46 79.3%	16 80%	22 81.5%	84 84.8%	26 76.5%	25 75.8%	79 80.6%	26 78.8%	28 93.3%	59 84.3%	411 81.9%
Baseline documentation regarding the atrial fibrillation (Number) [Number]
Persistent	20 34.5%	9 45%	10 37%	43 43.4%	13 38.2%	10 30.3%	37 37.8%	14 42.4%	12 40%	27 38.6%	195 38.8%
Permanent	23 39.7%	9 45%	11 40.7%	35 35.4%	11 32.4%	16 48.5%	37 37.8%	10 30.3%	14 46.7%	26 37.1%	192 38.2%
Paroxysmal	15 25.9%	2 10%	6 22.2%	21 21.2%	10 29.4%	7 21.2%	24 24.5%	9 27.3%	4 13.3%	17 24.3%	115 22.9%
Baseline documentation regarding stroke (Number) [Number]
No	54 93.1%	18 90%	24 88.9%	93 93.9%	30 88.2%	30 90.9%	91 92.9%	31 93.9%	26 86.7%	62 88.6%	459 91.4%
Yes	4 6.9%	2 10%	3 11.1%	6 6.1%	4 11.8%	3 9.1%	7 7.1%	2 6.1%	4 13.3%	8 11.4%	43 8.6%
Baseline documentation regarding transient ischemic attack (Number) [Number]
No	49 84.5%	20 100%	25 92.6%	88 88.9%	31 91.2%	31 93.9%	90 91.8%	30 90.9%	26 86.7%	63 90%	453 90.2%
Yes	9 15.5%	0 0%	2 7.4%	11 11.1%	3 8.8%	2 6.1%	8 8.2%	3 9.1%	4 13.3%	7 10%	49 9.8%
Baseline documentation regarding transient ischemic attack or stroke (Number) [Number]
No	45 77.6%	18 90%	23 85.2%	82 82.8%	27 79.4%	28 84.8%	85 86.7%	28 84.8%	22 73.3%	57 81.4%	415 82.7%
Yes	13 22.4%	2 10%	4 14.8%	17 17.2%	7 20.6%	5 15.2%	13 13.3%	5 15.2%	8 26.7%	13 18.6%	87 17.3%
Baseline documentation regarding hypertension (Number) [Number]
No	17 29.3%	10 50%	8 29.6%	21 21.2%	13 38.2%	14 42.4%	24 24.5%	8 24.2%	10 33.3%	21 30%	146 29.1%
Yes	41 70.7%	10 50%	19 70.4%	78 78.8%	21 61.8%	19 57.6%	74 75.5%	25 75.8%	20 66.7%	49 70%	356 70.9%
Baseline documentation regarding symptomatic heart failure (Number) [Number]
No	41 70.7%	12 60%	17 63%	73 73.7%	20 58.8%	21 63.6%	85 86.7%	20 60.6%	20 66.7%	46 65.7%	355 70.7%
Yes	17 29.3%	8 40%	10 37%	26 26.3%	14 41.2%	12 36.4%	13 13.3%	13 39.4%	10 33.3%	24 34.3%	147 29.3%
Baseline documentation regarding left ventricular dysfunction (Number) [Number]
No	41 70.7%	14 70%	17 63%	68 68.7%	22 64.7%	19 57.6%	78 79.6%	20 60.6%	14 46.7%	44 62.9%	337 67.1%
Yes	17 29.3%	6 30%	10 37%	31 31.3%	12 35.3%	14 42.4%	20 20.4%	13 39.4%	16 53.3%	26 37.1%	165 32.9%
Baseline documentation regarding symptomatic heart failure or left ventricular dysfunction (Number) [Number]
No	35 60.3%	10 50%	14 51.9%	55 55.6%	15 44.1%	17 51.5%	71 72.4%	14 42.4%	12 40%	34 48.6%	277 55.2%
Yes	23 39.7%	10 50%	13 48.1%	44 44.4%	19 55.9%	16 48.5%	27 27.6%	19 57.6%	18 60%	36 51.4%	225 44.8%
Coronary Artery Disease (participants) [Number]
no	39 67.2%	1 5%	1 3.7%	55 55.6%	3 8.8%	4 12.1%	62 63.3%	2 6.1%	1 3.3%	28 40%	196 39%
yes	19 32.8%	19 95%	26 96.3%	44 44.4%	31 91.2%	29 87.9%	36 36.7%	31 93.9%	29 96.7%	42 60%	306 61%
D-dimer at baseline N=(56;19;25;88;29;32;85;31;29;63;457) (ng/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/ml]	106.8 (104.1)	104.5 (62.9)	176.9 (389.9)	100.8 (94.5)	120.3 (95.4)	96.3 (64.3)	146.8 (210.9)	119.4 (95.5)	83.8 (48.8)	139.9 (251.9)	120.9 (173.7)
Soluble fibrin at baseline N=(53;16;23;88;27;29;92;30;25;65;448) (µg/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [µg/ml]	4.9 (4.4)	5.3 (7.9)	5.4 (5.9)	5.8 (8.8)	9.1 (15.5)	7.6 (14.8)	7.4 (11.5)	9.2 (26.0)	6.5 (9.2)	7.2 (10.4)	6.8 (11.9)
Thromboxane B2 (TXB2) measured at baseline N=(53;20;23;93;30;30;90;31;30;67;467) (pg/mg Creatinine) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pg/mg Creatinine]	3968.5 (2530.4)	3795.9 (2252.9)	4705.6 (3047.5)	4138.1 (2184.6)	4485.7 (2147.8)	4084.9 (2253.5)	3619.0 (2020.6)	4450.8 (2653.7)	3735.6 (2440.6)	4177.9 (2661.2)	4051.6 (2367.7)
ECT at baseline N=(57;20;27;98;34;33;95;33;29;56;482) (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	32.3 (2.0)	31.8 (1.9)	31.9 (2.2)	31.9 (2.2)	32.0 (1.9)	32.6 (2.4)	33.6 (13.3)	31.9 (1.8)	32.2 (2.6)	32.0 (2.4)	32.4 (6.2)
aPTT at baseline N=(57;20;27;98;34;33;96;33;29;57;484) (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	32.5 (3.0)	31.2 (3.5)	32.4 (3.6)	34.2 (15.2)	33.5 (7.6)	34.2 (6.7)	32.8 (5.7)	32.6 (3.4)	32.9 (6.7)	33.2 (3.7)	33.1 (8.2)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Fatal or Life-threatening Major Bleeding Events
Description	Retroperitoneal, intracranial, intraocular, or intraspinal bleeding, or requiring surgical treatment, or leading to a transfusion of 2 units or more, or leading to a fall in hemoglobin of 20g/L or more
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All treated patients. No statistical comparisons were performed, due to the extremely small number of events.

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	59	21	27	100	36	33	105	34	30	70
Number [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 3%	3 10%	0 0%

2. Primary Outcome

Title	Number of Participants With Minor/Relevant Bleeding Events
Description	Haematuria, rectal bleeding, gingival bleeding, skin hematoma of 25cm^2 or more, nose bleed of more than 5 minutes duration, bleeding leading to a hospitalization, leading to a transfusion of less than 2 units or any other clinically relevant bleeding
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All treated patients. No statistical comparisons were performed, due to the small number of events per group

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	59	21	27	100	36	33	105	34	30	70
Number [Participants]	0 0%	1 5%	1 3.7%	9 9.1%	2 5.9%	2 6.1%	6 6.1%	4 12.1%	3 10%	4 5.7%

3. Primary Outcome

Title	Number of Participants With Minor/Nuisance Bleeding Events
Description	All bleeding events not fulfilling one of the criteria for major bleeding event or minor/relevant bleeding events.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All treated patients. No statistical comparisons were performed, due to the small number of events per group

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	59	21	27	100	36	33	105	34	30	70
Number [Participants]	2 3.4%	1 5%	2 7.4%	6 6.1%	6 17.6%	5 15.2%	9 9.2%	7 21.2%	9 30%	9 12.9%

4. Secondary Outcome

Title	Number of Participants With Thromboembolic Events: Composite Endpoint
Description	Combination of ischemic stroke (fatal or non fatal), transient ischemic attack, systemic thromboembolism, myocardial infarction (fatal or non fatal), other major adverse cardiac event and all cause mortality
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All randomized patients. No statistical comparisons were performed, due to the extremely small number of events.

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	58	20	27	99	34	33	98	33	30	70
Number [Participants]	1 1.7%	2 10%	1 3.7%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Number of Participants With Thromboembolic Events: Ischemic Stroke
Description	Occurence of an ischemic stroke (fatal or non-fatal)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All randomized patients. No statistical comparisons were performed, due to the extremely small number of events.

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	58	20	27	99	34	33	98	33	30	70
None	58 100%	19 95%	27 100%	99 100%	34 100%	33 100%	98 100%	33 100%	30 100%	70 100%
Fatal	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Non-Fatal	0 0%	1 5%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Both	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

6. Secondary Outcome

Title	Thromboembolic Events: Number of Participants With Transient Ischemic Attack
Description	Occurence of a transient ischemic attack
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All randomized patients. No statistical comparisons were performed, due to the extremely small number of events.

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	58	20	27	99	34	33	98	33	30	70
Number [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

7. Secondary Outcome

Title	Thromboembolic Events: Number of Participants With Systemic Thromboembolism
Description	Occurence of a systemic thromboembolism
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All randomized patients. No statistical comparisons were performed, due to the extremely small number of events.

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	58	20	27	99	34	33	98	33	30	70
Number [Participants]	1 1.7%	1 5%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Thromboembolic Events: Number of Participants With Myocardial Infarction
Description	Occurence of a myocardial infarction
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All randomized patients. No statistical comparisons were performed, due to the extremely small number of events.

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	58	20	27	99	34	33	98	33	30	70
None	58 100%	20 100%	27 100%	99 100%	34 100%	33 100%	98 100%	33 100%	30 100%	70 100%
Fatal	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Non-Fatal	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Both	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

9. Secondary Outcome

Title	Thromboembolic Events: Number of Participants With Other Major Cardiac Events
Description	Occurence of other major adverse cardiac events
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All randomized patients. No statistical comparisons were performed, due to the extremely small number of events.

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	58	20	27	99	34	33	98	33	30	70
Number [Participants]	0 0%	1 5%	1 3.7%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

10. Secondary Outcome

Title	Thromboembolic Events: Number of Participants Who Died
Description	Occurence of death by all causes
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All randomized patients. No statistical comparisons were performed, due to the extremely small number of events.

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	58	20	27	99	34	33	98	33	30	70
Number [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

11. Secondary Outcome

Title	D-dimer: Difference From Baseline
Description	Difference in D-dimer from baseline to last available value
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All randomised patients, only per-protocol data included.

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	55	19	26	87	29	32	88	29	29	63
Mean (Standard Deviation) [ng/ml]	22.3 (65.4)	12.3 (25.3)	50.2 (182.8)	8.1 (41.6)	29.1 (90.4)	8.6 (49.2)	4.2 (95.8)	11.3 (82.2)	-7.9 (40.9)	-5.8 (50.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BIBR 1048 50 mg b.i.d, BIBR 1048 50 mg b.i.d + ASA 81 mg q.d., BIBR 1048 50 mg b.i.d + ASA 325 mg qd, BIBR 1048 150 mg b.i.d, BIBR 1048 150 mg b.i.d + ASA 81 mg qd, BIBR 1048 150 mg b.i.d + ASA 325 mg qd, BIBR 1048 300 mg b.i.d, BIBR 1048 300 mg b.i.d + ASA 81 mg qd, BIBR 1048 300 mg b.i.d + ASA 325 mg qd, Warfarin, Dosed to Target INR 2.0 to 3.0
	Comments	Group comparison of differences from baseline to last available value
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0357
	Comments
	Method	Kruskal-Wallis
	Comments

12. Secondary Outcome

Title	Soluble Fibrin: Difference From Baseline
Description	Difference from baseline to visit 7
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All randomised patients, only per-protocol data included.

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	52	15	25	88	25	24	83	27	20	54
Mean (Standard Deviation) [µg/ml]	3.2 (22.0)	0.9 (2.3)	1.2 (8.4)	0.3 (5.1)	-2.0 (9.9)	-1.3 (8.8)	2.3 (26.8)	-0.7 (4.6)	-1.9 (12.0)	0.1 (4.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BIBR 1048 50 mg b.i.d, BIBR 1048 50 mg b.i.d + ASA 81 mg q.d., BIBR 1048 50 mg b.i.d + ASA 325 mg qd, BIBR 1048 150 mg b.i.d, BIBR 1048 150 mg b.i.d + ASA 81 mg qd, BIBR 1048 150 mg b.i.d + ASA 325 mg qd, BIBR 1048 300 mg b.i.d, BIBR 1048 300 mg b.i.d + ASA 81 mg qd, BIBR 1048 300 mg b.i.d + ASA 325 mg qd, Warfarin, Dosed to Target INR 2.0 to 3.0
	Comments	Group comparison of differences from baseline to week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.26711
	Comments
	Method	Kruskal-Wallis
	Comments

13. Secondary Outcome

Title	11-dehydrothromboxane B2 (TXB2): Difference From Baseline
Description	Difference from baseline to visit 7
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All treated patients. No statistical comparisons due to high variability

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	44	17	19	73	25	27	73	25	25	51
Mean (Standard Deviation) [pg/mg Creatinine]	596.5 (2896.3)	-1816.8 (2186.1)	-2779.8 (2953.3)	922.0 (3874.0)	-1988.6 (2187.5)	-1125.9 (3566.6)	1059.7 (2216.8)	-1822.6 (2381.7)	-1337.8 (2279.2)	203.5 (2109.0)

14. Secondary Outcome

Title	Ecarin Clotting Time (ECT): Difference From Baseline
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All treated patients. No statistical comparisons due to high variability

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	56	19	26	94	34	33	86	29	27	27
Mean (Standard Deviation) [seconds]	9.7 (8.2)	12.0 (10.7)	12.0 (9.6)	31.9 (26.2)	42.5 (29.2)	32.7 (23.1)	63.6 (44.8)	70.8 (60.3)	74.0 (70.5)	3.1 (2.5)

15. Secondary Outcome

Title	Activated Partial Thromboplastin Time (aPTT): Difference From Baseline
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All treated patients. No statistical comparisons due to high variability

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	56	19	26	92	33	33	87	29	27	27
Mean (Standard Deviation) [seconds]	6.4 (5.6)	8.3 (6.1)	8.8 (9.4)	13.5 (18.3)	24.9 (26.1)	14.5 (11.5)	25.0 (12.4)	23.4 (12.7)	27.2 (24.2)	8.8 (6.7)

16. Secondary Outcome

Title	Trough Plasma Concentration of Dabigatran (BIBR 953)
Description	The values of the trough plasma concentration of dabigatran (BIBR 953) are the by-patient geometric means of week 1, 4 and 12.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All treated patients

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	58	20	27	99	34	33	97	33	30	70
Mean (Standard Deviation) [ng/ml]	29.1 (16.6)	30.4 (16.6)	31.8 (20.0)	82.8 (54.3)	103.2 (69.0)	90.1 (52.5)	188.0 (117.3)	203.7 (123.9)	207.6 (108.7)	NA (NA)

17. Secondary Outcome

Title	Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline
Description	Increase of AST to more than two times the baseline value
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All treated patients. No statistical comparisons due to extremely small number of cases

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	58	20	27	99	34	33	98	33	30	70
Missing	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1%	1 3%	0 0%	1 1.4%
No	57 98.3%	20 100%	24 88.9%	93 93.9%	32 94.1%	31 93.9%	95 96.9%	31 93.9%	30 100%	68 97.1%
Yes	1 1.7%	0 0%	3 11.1%	6 6.1%	2 5.9%	2 6.1%	2 2%	1 3%	0 0%	1 1.4%

18. Secondary Outcome

Title	Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline
Description	Increase of AP to more than two times the baseline value
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All treated patients. No statistical comparisons due to extremely small number of cases

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	58	20	27	99	34	33	98	33	30	70
Missing	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1%	1 3%	0 0%	1 1.4%
No	58 100%	20 100%	27 100%	98 99%	33 97.1%	33 100%	97 99%	32 97%	29 96.7%	69 98.6%
Yes	0 0%	0 0%	0 0%	1 1%	1 2.9%	0 0%	0 0%	0 0%	1 3.3%	0 0%

19. Secondary Outcome

Title	Number of Participants With Increase of Bilirubin to >2*Baseline
Description	Increase of Bilirubin to more than two times the baseline value
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All treated patients. No statistical comparisons due to extremely small number of cases

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	58	20	27	99	34	33	98	33	30	70
Missing	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1%	1 3%	0 0%	1 1.4%
No	55 94.8%	18 90%	25 92.6%	86 86.9%	31 91.2%	33 100%	88 89.8%	29 87.9%	29 96.7%	63 90%
Yes	3 5.2%	2 10%	2 7.4%	13 13.1%	3 8.8%	0 0%	9 9.2%	3 9.1%	1 3.3%	6 8.6%

20. Secondary Outcome

Title	Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline
Description	Number of Participants with Increase of ALT to more than two times the baseline value
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All treated patients. No statistical comparisons due to extremely small number of cases

Arm/Group Title	BIBR 1048 50 mg b.i.d	BIBR 1048 50 mg b.i.d + ASA 81 mg q.d.	BIBR 1048 50 mg b.i.d + ASA 325 mg qd	BIBR 1048 150 mg b.i.d	BIBR 1048 150 mg b.i.d + ASA 81 mg qd	BIBR 1048 150 mg b.i.d + ASA 325 mg qd	BIBR 1048 300 mg b.i.d	BIBR 1048 300 mg b.i.d + ASA 81 mg qd	BIBR 1048 300 mg b.i.d + ASA 325 mg qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral	bid (twice daily) oral + qd (once daily) oral	bid (twice daily) oral + qd (once daily) oral	qd (once daily) oral
Measure Participants	58	20	27	99	34	33	98	33	30	70
Missing	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1%	1 3%	0 0%	1 1.4%
No	55 94.8%	18 90%	26 96.3%	95 96%	33 97.1%	32 97%	93 94.9%	31 93.9%	30 100%	64 91.4%
Yes	3 5.2%	2 10%	1 3.7%	4 4%	1 2.9%	1 3%	4 4.1%	1 3%	0 0%	5 7.1%

21. Secondary Outcome

Title	Severity of Adverse Events
Description	Total number of patients with any adverse event of worst intensity 'mild', 'moderate' and 'severe'.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Treated patients(Numbers of patients for adverse events are counted for each treatment and are in their sum greater than the total number of patients randomized as 14 patients on Dabigatran with ASA changed treatment,12 patients down titrated Dabigatran bid to qd of which one did the down titration at the same time as the stop of the ASA treatment)

Arm/Group Title	D50bid	D50qd	D50bid + ASA81qd	D50bid + ASA325qd	D150bid	D150qd	D150bid + ASA81qd	D150qd + ASA81qd	D150bid + ASA325qd	D150qd + ASA325qd	D300bid	D300qd	D300bid + ASA81qd	D300qd + ASA81qd	D300bid + ASA325qd	D300qd + ASA325qd	Warfarin, Dosed to Target INR 2.0 to 3.0
Arm/Group Description	Dabigatran 50 mg twice daily	Dabigatran 50 mg once daily	Dabigatran 50 mg twice daily + ASA 81 mg once daily	Dabigatran 50 mg twice daily + ASA 325 mg once daily	Dabigatran 150 mg twice daily	Dabigatran 150 mg once daily	Dabigatran 150 mg twice daily + ASA 81 mg once daily	Dabigatran 150 mg once daily + ASA 81 mg once daily	Dabigatran 150 mg twice daily + ASA 325 mg once daily	Dabigatran 150 mg once daily + ASA 325 mg once daily	Dabigatran 300 mg twice daily	Dabigatran 300 mg once daily	Dabigatran 300 mg twice daily + ASA 81 mg once daily	Dabigatran 300 mg once daily + ASA 81 mg once daily	Dabigatran 300 mg twice daily + ASA 325 mg once daily	Dabigatran 300 mg once daily + ASA 325 mg once daily	Warfarin once daily
Measure Participants	59	1	21	27	100	3	36	1	33	1	105	3	34	2	30	1	70
Mild	24 41.4%	0 0%	9 33.3%	16 16.2%	54 158.8%	1 3%	23 23.5%	0 0%	17 56.7%	0 0%	47 9.4%	1 NaN	23 NaN	2 NaN	23 NaN	1 NaN	30 NaN
Moderate	13 22.4%	0 0%	6 22.2%	7 7.1%	19 55.9%	0 0%	9 9.2%	0 0%	4 13.3%	0 0%	23 4.6%	0 NaN	5 NaN	1 NaN	11 NaN	1 NaN	14 NaN
Severe	3 5.2%	0 0%	1 3.7%	1 1%	4 11.8%	0 0%	2 2%	0 0%	1 3.3%	0 0%	6 1.2%	0 NaN	1 NaN	0 NaN	2 NaN	0 NaN	2 NaN

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	Note that it was foreseen per protocol that all treatments were possibly to be down-titrated to BIBR 1048 q.d.; criteria included creatinine clearance and aPTT. Events are counted to the treatment on which they occurred.
Arm/Group Title	D50bid		D50qd		D50bid + ASA81qd		D50bid + ASA325qd		D150bid		D150qd		D150bid + ASA81qd		D150qd + ASA81qd		D150bid + ASA325qd		D150qd + ASA325qd		D300bid		D300qd		D300bid + ASA81qd		D300qd + ASA81qd		D300bid + ASA325qd		D300qd + ASA325qd		Warfarin
Arm/Group Description	Dabigatran 50 mg twice daily		Dabigatran 50 mg once daily		Dabigatran 50 mg twice daily + ASA 81 mg once daily		Dabigatran 50 mg twice daily + ASA 325 mg once daily		Dabigatran 150 mg twice daily		Dabigatran 150 mg once daily		Dabigatran 150 mg twice daily + ASA 81 mg once daily		Dabigatran 150 mg once daily + ASA 81 mg once daily		Dabigatran 150 mg twice daily + ASA 325 mg once daily		Dabigatran 150 mg once daily + ASA 325 mg once daily		Dabigatran 300 mg twice daily		Dabigatran 300 mg once daily		Dabigatran 300 mg twice daily + ASA 81 mg once daily		Dabigatran 300 mg once daily + ASA 81 mg once daily		Dabigatran 300 mg twice daily + ASA 325 mg once daily		Dabigatran 300 mg once daily + ASA 325 mg once daily		Warfarin once daily
All Cause Mortality
	D50bid		D50qd		D50bid + ASA81qd		D50bid + ASA325qd		D150bid		D150qd		D150bid + ASA81qd		D150qd + ASA81qd		D150bid + ASA325qd		D150qd + ASA325qd		D300bid		D300qd		D300bid + ASA81qd		D300qd + ASA81qd		D300bid + ASA325qd		D300qd + ASA325qd		Warfarin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	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)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	D50bid		D50qd		D50bid + ASA81qd		D50bid + ASA325qd		D150bid		D150qd		D150bid + ASA81qd		D150qd + ASA81qd		D150bid + ASA325qd		D150qd + ASA325qd		D300bid		D300qd		D300bid + ASA81qd		D300qd + ASA81qd		D300bid + ASA325qd		D300qd + ASA325qd		Warfarin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	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	5/59 (8.5%)		0/1 (0%)		2/21 (9.5%)		1/27 (3.7%)		10/100 (10%)		0/3 (0%)		4/36 (11.1%)		0/1 (0%)		2/33 (6.1%)		0/1 (0%)		3/105 (2.9%)		0/3 (0%)		4/34 (11.8%)		0/2 (0%)		4/30 (13.3%)		0/1 (0%)		2/70 (2.9%)
Cardiac disorders
Acute coronary syndrome	0/59 (0%)		0/1 (0%)		1/21 (4.8%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		1/34 (2.9%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Angina pectoris	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		1/100 (1%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Atrial fibrillation	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		1/105 (1%)		0/3 (0%)		1/34 (2.9%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		1/70 (1.4%)
Atrial thrombosis	0/59 (0%)		0/1 (0%)		1/21 (4.8%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Cardiac failure	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		1/100 (1%)		0/3 (0%)		2/36 (5.6%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Cardiac failure congestive	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Ventricular fibrillation	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		1/100 (1%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Ventricular tachycardia	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		1/100 (1%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Gastrointestinal disorders
Abdominal pain	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Dyspepsia	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		1/100 (1%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Gastric ulcer	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		1/34 (2.9%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Gastrointestinal haemorrhage	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		1/34 (2.9%)		0/2 (0%)		1/30 (3.3%)		0/1 (0%)		0/70 (0%)
Ileus	0/59 (0%)		0/1 (0%)		0/21 (0%)		1/27 (3.7%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Lower gastrointestinal haemorrhage	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		1/30 (3.3%)		0/1 (0%)		0/70 (0%)
Oesophageal ulcer	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		1/34 (2.9%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Pancreatitis	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Rectal haemorrhage	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		1/30 (3.3%)		0/1 (0%)		0/70 (0%)
General disorders
Asthenia	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Chest pain	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		1/100 (1%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Hepatobiliary disorders
Cholecystitis	1/59 (1.7%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Cholelithiasis	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		1/100 (1%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Infections and infestations
Diverticulitis	1/59 (1.7%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Pneumonia	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		2/100 (2%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Urinary tract infection	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Injury, poisoning and procedural complications
Implantable defibrillator malfunction	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Radius fracture	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		1/70 (1.4%)
Investigations
Alanine aminotransferase increased	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		1/100 (1%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Blood pressure systolic inspiratory decreased	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Metabolism and nutrition disorders
Hypokalaemia	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Musculoskeletal and connective tissue disorders
Neck pain	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Pain in extremity	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		2/100 (2%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Colon cancer	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		1/30 (3.3%)		0/1 (0%)		0/70 (0%)
Nervous system disorders
Cerebrovascular accident	0/59 (0%)		0/1 (0%)		1/21 (4.8%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Epilepsy	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		1/105 (1%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Paraesthesia	1/59 (1.7%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Syncope	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		1/105 (1%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Renal and urinary disorders
Renal infarct	0/59 (0%)		0/1 (0%)		1/21 (4.8%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		1/30 (3.3%)		0/1 (0%)		0/70 (0%)
Respiratory distress	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Skin and subcutaneous tissue disorders
Skin discolouration	1/59 (1.7%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Surgical and medical procedures
Hip arthroplasty	1/59 (1.7%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Vascular disorders
Circulatory collapse	1/59 (1.7%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Hypotension	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Peripheral embolism	1/59 (1.7%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Other (Not Including Serious) Adverse Events
	D50bid		D50qd		D50bid + ASA81qd		D50bid + ASA325qd		D150bid		D150qd		D150bid + ASA81qd		D150qd + ASA81qd		D150bid + ASA325qd		D150qd + ASA325qd		D300bid		D300qd		D300bid + ASA81qd		D300qd + ASA81qd		D300bid + ASA325qd		D300qd + ASA325qd		Warfarin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	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	20/59 (33.9%)		0/1 (0%)		9/21 (42.9%)		14/27 (51.9%)		43/100 (43%)		1/3 (33.3%)		19/36 (52.8%)		0/1 (0%)		15/33 (45.5%)		0/1 (0%)		35/105 (33.3%)		1/3 (33.3%)		20/34 (58.8%)		2/2 (100%)		18/30 (60%)		1/1 (100%)		22/70 (31.4%)
Cardiac disorders
Angina pectoris	0/59 (0%)		0/1 (0%)		0/21 (0%)		1/27 (3.7%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		1/105 (1%)		0/3 (0%)		2/34 (5.9%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		1/70 (1.4%)
Eye disorders
Conjunctival haemorrhage	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		2/36 (5.6%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		1/34 (2.9%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Eye haemorrhage	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		2/36 (5.6%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		2/105 (1.9%)		0/3 (0%)		1/34 (2.9%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Gastrointestinal disorders
Abdominal distension	1/59 (1.7%)		0/1 (0%)		2/21 (9.5%)		0/27 (0%)		1/100 (1%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		1/1 (100%)		0/70 (0%)
Abdominal pain	1/59 (1.7%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		1/100 (1%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		2/105 (1.9%)		0/3 (0%)		0/34 (0%)		1/2 (50%)		0/30 (0%)		0/1 (0%)		1/70 (1.4%)
Abdominal pain upper	2/59 (3.4%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		1/100 (1%)		0/3 (0%)		3/36 (8.3%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		3/105 (2.9%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		1/30 (3.3%)		0/1 (0%)		0/70 (0%)
Constipation	2/59 (3.4%)		0/1 (0%)		1/21 (4.8%)		4/27 (14.8%)		0/100 (0%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		2/70 (2.9%)
Diarrhoea	3/59 (5.1%)		0/1 (0%)		2/21 (9.5%)		3/27 (11.1%)		3/100 (3%)		0/3 (0%)		2/36 (5.6%)		0/1 (0%)		2/33 (6.1%)		0/1 (0%)		3/105 (2.9%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		2/30 (6.7%)		0/1 (0%)		1/70 (1.4%)
Dry mouth	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		1/105 (1%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		2/30 (6.7%)		0/1 (0%)		0/70 (0%)
Dyspepsia	1/59 (1.7%)		0/1 (0%)		1/21 (4.8%)		1/27 (3.7%)		3/100 (3%)		0/3 (0%)		3/36 (8.3%)		0/1 (0%)		2/33 (6.1%)		0/1 (0%)		6/105 (5.7%)		0/3 (0%)		1/34 (2.9%)		0/2 (0%)		2/30 (6.7%)		0/1 (0%)		0/70 (0%)
Gingival bleeding	0/59 (0%)		0/1 (0%)		0/21 (0%)		1/27 (3.7%)		1/100 (1%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		1/105 (1%)		0/3 (0%)		2/34 (5.9%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Haemorrhoidal haemorrhage	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		1/100 (1%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		1/34 (2.9%)		0/2 (0%)		2/30 (6.7%)		0/1 (0%)		1/70 (1.4%)
Mouth haemorrhage	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		2/34 (5.9%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Nausea	2/59 (3.4%)		0/1 (0%)		2/21 (9.5%)		0/27 (0%)		4/100 (4%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		1/105 (1%)		0/3 (0%)		2/34 (5.9%)		1/2 (50%)		1/30 (3.3%)		0/1 (0%)		0/70 (0%)
Vomiting	1/59 (1.7%)		0/1 (0%)		0/21 (0%)		2/27 (7.4%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		1/2 (50%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
General disorders
Chest pain	0/59 (0%)		0/1 (0%)		2/21 (9.5%)		0/27 (0%)		2/100 (2%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		3/105 (2.9%)		0/3 (0%)		2/34 (5.9%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		1/70 (1.4%)
Fatigue	1/59 (1.7%)		0/1 (0%)		0/21 (0%)		2/27 (7.4%)		5/100 (5%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		3/105 (2.9%)		0/3 (0%)		5/34 (14.7%)		1/2 (50%)		1/30 (3.3%)		0/1 (0%)		3/70 (4.3%)
Sensation of pressure	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		1/2 (50%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Infections and infestations
Influenza	1/59 (1.7%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		2/34 (5.9%)		0/2 (0%)		1/30 (3.3%)		0/1 (0%)		0/70 (0%)
Nasopharyngitis	2/59 (3.4%)		0/1 (0%)		0/21 (0%)		1/27 (3.7%)		0/100 (0%)		0/3 (0%)		2/36 (5.6%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		3/105 (2.9%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		1/30 (3.3%)		0/1 (0%)		0/70 (0%)
Urinary tract infection	1/59 (1.7%)		0/1 (0%)		1/21 (4.8%)		0/27 (0%)		2/100 (2%)		1/3 (33.3%)		2/36 (5.6%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		1/105 (1%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		1/30 (3.3%)		0/1 (0%)		1/70 (1.4%)
Injury, poisoning and procedural complications
Contusion	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		2/100 (2%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		2/33 (6.1%)		0/1 (0%)		3/105 (2.9%)		0/3 (0%)		2/34 (5.9%)		0/2 (0%)		3/30 (10%)		0/1 (0%)		6/70 (8.6%)
Investigations
Alanine aminotransferase increased	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		1/105 (1%)		0/3 (0%)		0/34 (0%)		1/2 (50%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Aspartate aminotransferase increased	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		1/105 (1%)		0/3 (0%)		0/34 (0%)		1/2 (50%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/59 (0%)		0/1 (0%)		2/21 (9.5%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		1/105 (1%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		2/70 (2.9%)
Costochondritis	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		1/2 (50%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Pain in extremity	2/59 (3.4%)		0/1 (0%)		2/21 (9.5%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		2/36 (5.6%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Nervous system disorders
Dizziness	3/59 (5.1%)		0/1 (0%)		1/21 (4.8%)		3/27 (11.1%)		4/100 (4%)		0/3 (0%)		2/36 (5.6%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		4/105 (3.8%)		0/3 (0%)		2/34 (5.9%)		1/2 (50%)		5/30 (16.7%)		1/1 (100%)		2/70 (2.9%)
Headache	2/59 (3.4%)		0/1 (0%)		1/21 (4.8%)		4/27 (14.8%)		2/100 (2%)		0/3 (0%)		2/36 (5.6%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		3/105 (2.9%)		0/3 (0%)		1/34 (2.9%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		2/70 (2.9%)
Renal and urinary disorders
Haematuria	1/59 (1.7%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		7/100 (7%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		2/105 (1.9%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		1/30 (3.3%)		0/1 (0%)		0/70 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/59 (1.7%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		3/100 (3%)		0/3 (0%)		3/36 (8.3%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		3/105 (2.9%)		0/3 (0%)		1/34 (2.9%)		1/2 (50%)		1/30 (3.3%)		0/1 (0%)		1/70 (1.4%)
Dyspnoea	0/59 (0%)		0/1 (0%)		0/21 (0%)		1/27 (3.7%)		4/100 (4%)		0/3 (0%)		2/36 (5.6%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		2/105 (1.9%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		1/70 (1.4%)
Epistaxis	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		1/100 (1%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		4/105 (3.8%)		0/3 (0%)		2/34 (5.9%)		0/2 (0%)		2/30 (6.7%)		0/1 (0%)		5/70 (7.1%)
Skin and subcutaneous tissue disorders
Ecchymosis	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		2/33 (6.1%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		1/34 (2.9%)		0/2 (0%)		2/30 (6.7%)		0/1 (0%)		2/70 (2.9%)
Exanthem	0/59 (0%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		0/100 (0%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		1/3 (33.3%)		0/34 (0%)		0/2 (0%)		0/30 (0%)		0/1 (0%)		0/70 (0%)
Vascular disorders
Haematoma	1/59 (1.7%)		0/1 (0%)		0/21 (0%)		0/27 (0%)		2/100 (2%)		0/3 (0%)		1/36 (2.8%)		0/1 (0%)		1/33 (3%)		0/1 (0%)		1/105 (1%)		0/3 (0%)		1/34 (2.9%)		0/2 (0%)		2/30 (6.7%)		0/1 (0%)		0/70 (0%)
Hypertension	1/59 (1.7%)		0/1 (0%)		1/21 (4.8%)		0/27 (0%)		5/100 (5%)		0/3 (0%)		0/36 (0%)		0/1 (0%)		0/33 (0%)		0/1 (0%)		0/105 (0%)		0/3 (0%)		0/34 (0%)		0/2 (0%)		2/30 (6.7%)		0/1 (0%)		1/70 (1.4%)

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.