Atrial Fibrillation
Conditions
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.
Interventions
DRUGwarfarin
comparator
DRUGdabigatran without ASA
dose comparison
DRUGdabigatran with ASA
dose comparison in combination
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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: 1. hypertension (defined as systolic bloodpressure (SBP) \> 140 mmHg and/or diastolic bloodpressure (DBP) \> 90 mm Hg) requiring antihypertensive medical treatment. 2. diabetes mellitus (type I and II). 3. symptomatic heart failure or left ventricular dysfunction (ejection fraction (EF) \< 40%). 4. a previous ischemic stroke or transient ischemic attack. 5. age greater than 75 years. 6. history of coronary artery disease (by amendment 4) 4. 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. 5. Age \> = 18 years at entry. 6. 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Thromboembolic Events: Number of Participants With Systemic Thromboembolism | 12 weeks | Occurence of a systemic thromboembolism |
| Thromboembolic Events: Number of Participants With Myocardial Infarction | 12 weeks | Occurence of a myocardial infarction |
| Thromboembolic Events: Number of Participants With Other Major Cardiac Events | 12 weeks | Occurence of other major adverse cardiac events |
| Thromboembolic Events: Number of Participants Who Died | 12 weeks | Occurence of death by all causes |
| D-dimer: Difference From Baseline | baseline and 12 weeks | Difference in D-dimer from baseline to last available value |
| Soluble Fibrin: Difference From Baseline | baseline and 12 weeks | Difference from baseline to visit 7 |
| 11-dehydrothromboxane B2 (TXB2): Difference From Baseline | baseline and 12 weeks | Difference from baseline to visit 7 |
| 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 |
| Activated Partial Thromboplastin Time (aPTT): Difference From Baseline | baseline and 12 weeks | — |
| 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. |
| 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 |
| 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 |
| Number of Participants With Increase of Bilirubin to >2*Baseline | 12 weeks | Increase of Bilirubin to more than two times the baseline value |
| 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 |
| Severity of Adverse Events | 12 weeks | Total number of patients with any adverse event of worst intensity 'mild', 'moderate' and 'severe'. |
| Ecarin Clotting Time (ECT): Difference From Baseline | baseline and 12 weeks | — |
| Number of Participants With Thromboembolic Events: Ischemic Stroke | 12 weeks | Occurence of an ischemic stroke (fatal or non-fatal) |
| Thromboembolic Events: Number of Participants With Transient Ischemic Attack | 12 weeks | Occurence of a transient ischemic attack |
Countries
Denmark, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BIBR 1048 50 mg b.i.d bid (twice daily) oral | 58 |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. bid (twice daily) oral + qd (once daily) oral | 20 |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd bid (twice daily) oral + qd (once daily) oral | 27 |
| BIBR 1048 150 mg b.i.d bid (twice daily) oral | 99 |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd bid (twice daily) oral + qd (once daily) oral | 34 |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd bid (twice daily) oral + qd (once daily) oral | 33 |
| BIBR 1048 300 mg b.i.d bid (twice daily) oral | 98 |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd bid (twice daily) oral + qd (once daily) oral | 33 |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd bid (twice daily) oral + qd (once daily) oral | 30 |
| Warfarin, Dosed to Target INR 2.0 to 3.0 qd (once daily) oral | 70 |
| Total | 502 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 1 | 6 | 1 | 1 | 6 | 6 | 4 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 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 | BIBR 1048 50 mg b.i.d | Warfarin, Dosed to Target INR 2.0 to 3.0 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 70.1 Years STANDARD_DEVIATION 9.4 | 71.6 Years STANDARD_DEVIATION 8.1 | 69.7 Years STANDARD_DEVIATION 7.7 | 72.1 Years STANDARD_DEVIATION 9 | 69.7 Years STANDARD_DEVIATION 8 | 69.0 Years STANDARD_DEVIATION 9.1 | 71.8 Years STANDARD_DEVIATION 7.2 | 68.6 Years STANDARD_DEVIATION 7.1 | 69.0 Years STANDARD_DEVIATION 8.8 | 69.0 Years STANDARD_DEVIATION 8.3 | 69.7 Years STANDARD_DEVIATION 8.3 |
| aPTT at baseline N=(57;20;27;98;34;33;96;33;29;57;484) | 31.2 seconds STANDARD_DEVIATION 3.5 | 32.4 seconds STANDARD_DEVIATION 3.6 | 34.2 seconds STANDARD_DEVIATION 15.2 | 33.5 seconds STANDARD_DEVIATION 7.6 | 34.2 seconds STANDARD_DEVIATION 6.7 | 32.8 seconds STANDARD_DEVIATION 5.7 | 32.6 seconds STANDARD_DEVIATION 3.4 | 32.9 seconds STANDARD_DEVIATION 6.7 | 32.5 seconds STANDARD_DEVIATION 3 | 33.2 seconds STANDARD_DEVIATION 3.7 | 33.1 seconds STANDARD_DEVIATION 8.2 |
| Baseline documentation regarding hypertension No | 10 Participants | 8 Participants | 21 Participants | 13 Participants | 14 Participants | 24 Participants | 8 Participants | 10 Participants | 17 Participants | 21 Participants | 146 Participants |
| Baseline documentation regarding hypertension Yes | 10 Participants | 19 Participants | 78 Participants | 21 Participants | 19 Participants | 74 Participants | 25 Participants | 20 Participants | 41 Participants | 49 Participants | 356 Participants |
| Baseline documentation regarding left ventricular dysfunction No | 14 Participants | 17 Participants | 68 Participants | 22 Participants | 19 Participants | 78 Participants | 20 Participants | 14 Participants | 41 Participants | 44 Participants | 337 Participants |
| Baseline documentation regarding left ventricular dysfunction Yes | 6 Participants | 10 Participants | 31 Participants | 12 Participants | 14 Participants | 20 Participants | 13 Participants | 16 Participants | 17 Participants | 26 Participants | 165 Participants |
| Baseline documentation regarding stroke No | 18 Participants | 24 Participants | 93 Participants | 30 Participants | 30 Participants | 91 Participants | 31 Participants | 26 Participants | 54 Participants | 62 Participants | 459 Participants |
| Baseline documentation regarding stroke Yes | 2 Participants | 3 Participants | 6 Participants | 4 Participants | 3 Participants | 7 Participants | 2 Participants | 4 Participants | 4 Participants | 8 Participants | 43 Participants |
| Baseline documentation regarding symptomatic heart failure No | 12 Participants | 17 Participants | 73 Participants | 20 Participants | 21 Participants | 85 Participants | 20 Participants | 20 Participants | 41 Participants | 46 Participants | 355 Participants |
| Baseline documentation regarding symptomatic heart failure Yes | 8 Participants | 10 Participants | 26 Participants | 14 Participants | 12 Participants | 13 Participants | 13 Participants | 10 Participants | 17 Participants | 24 Participants | 147 Participants |
| Baseline documentation regarding symptomatic heart failure or left ventricular dysfunction No | 10 Participants | 14 Participants | 55 Participants | 15 Participants | 17 Participants | 71 Participants | 14 Participants | 12 Participants | 35 Participants | 34 Participants | 277 Participants |
| Baseline documentation regarding symptomatic heart failure or left ventricular dysfunction Yes | 10 Participants | 13 Participants | 44 Participants | 19 Participants | 16 Participants | 27 Participants | 19 Participants | 18 Participants | 23 Participants | 36 Participants | 225 Participants |
| Baseline documentation regarding the atrial fibrillation Paroxysmal | 2 Participants | 6 Participants | 21 Participants | 10 Participants | 7 Participants | 24 Participants | 9 Participants | 4 Participants | 15 Participants | 17 Participants | 115 Participants |
| Baseline documentation regarding the atrial fibrillation Permanent | 9 Participants | 11 Participants | 35 Participants | 11 Participants | 16 Participants | 37 Participants | 10 Participants | 14 Participants | 23 Participants | 26 Participants | 192 Participants |
| Baseline documentation regarding the atrial fibrillation Persistent | 9 Participants | 10 Participants | 43 Participants | 13 Participants | 10 Participants | 37 Participants | 14 Participants | 12 Participants | 20 Participants | 27 Participants | 195 Participants |
| Baseline documentation regarding transient ischemic attack No | 20 Participants | 25 Participants | 88 Participants | 31 Participants | 31 Participants | 90 Participants | 30 Participants | 26 Participants | 49 Participants | 63 Participants | 453 Participants |
| Baseline documentation regarding transient ischemic attack Yes | 0 Participants | 2 Participants | 11 Participants | 3 Participants | 2 Participants | 8 Participants | 3 Participants | 4 Participants | 9 Participants | 7 Participants | 49 Participants |
| Baseline documentation regarding transient ischemic attack or stroke No | 18 Participants | 23 Participants | 82 Participants | 27 Participants | 28 Participants | 85 Participants | 28 Participants | 22 Participants | 45 Participants | 57 Participants | 415 Participants |
| Baseline documentation regarding transient ischemic attack or stroke Yes | 2 Participants | 4 Participants | 17 Participants | 7 Participants | 5 Participants | 13 Participants | 5 Participants | 8 Participants | 13 Participants | 13 Participants | 87 Participants |
| Coronary Artery Disease no | 1 participants | 1 participants | 55 participants | 3 participants | 4 participants | 62 participants | 2 participants | 1 participants | 39 participants | 28 participants | 196 participants |
| Coronary Artery Disease yes | 19 participants | 26 participants | 44 participants | 31 participants | 29 participants | 36 participants | 31 participants | 29 participants | 19 participants | 42 participants | 306 participants |
| D-dimer at baseline N=(56;19;25;88;29;32;85;31;29;63;457) | 104.5 ng/ml STANDARD_DEVIATION 62.9 | 176.9 ng/ml STANDARD_DEVIATION 389.9 | 100.8 ng/ml STANDARD_DEVIATION 94.5 | 120.3 ng/ml STANDARD_DEVIATION 95.4 | 96.3 ng/ml STANDARD_DEVIATION 64.3 | 146.8 ng/ml STANDARD_DEVIATION 210.9 | 119.4 ng/ml STANDARD_DEVIATION 95.5 | 83.8 ng/ml STANDARD_DEVIATION 48.8 | 106.8 ng/ml STANDARD_DEVIATION 104.1 | 139.9 ng/ml STANDARD_DEVIATION 251.9 | 120.9 ng/ml STANDARD_DEVIATION 173.7 |
| ECT at baseline N=(57;20;27;98;34;33;95;33;29;56;482) | 31.8 seconds STANDARD_DEVIATION 1.9 | 31.9 seconds STANDARD_DEVIATION 2.2 | 31.9 seconds STANDARD_DEVIATION 2.2 | 32.0 seconds STANDARD_DEVIATION 1.9 | 32.6 seconds STANDARD_DEVIATION 2.4 | 33.6 seconds STANDARD_DEVIATION 13.3 | 31.9 seconds STANDARD_DEVIATION 1.8 | 32.2 seconds STANDARD_DEVIATION 2.6 | 32.3 seconds STANDARD_DEVIATION 2 | 32.0 seconds STANDARD_DEVIATION 2.4 | 32.4 seconds STANDARD_DEVIATION 6.2 |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 15 Participants | 8 Participants | 8 Participants | 19 Participants | 7 Participants | 2 Participants | 12 Participants | 11 Participants | 91 Participants |
| Sex: Female, Male Male | 16 Participants | 22 Participants | 84 Participants | 26 Participants | 25 Participants | 79 Participants | 26 Participants | 28 Participants | 46 Participants | 59 Participants | 411 Participants |
| Soluble fibrin at baseline N=(53;16;23;88;27;29;92;30;25;65;448) | 5.3 µg/ml STANDARD_DEVIATION 7.9 | 5.4 µg/ml STANDARD_DEVIATION 5.9 | 5.8 µg/ml STANDARD_DEVIATION 8.8 | 9.1 µg/ml STANDARD_DEVIATION 15.5 | 7.6 µg/ml STANDARD_DEVIATION 14.8 | 7.4 µg/ml STANDARD_DEVIATION 11.5 | 9.2 µg/ml STANDARD_DEVIATION 26 | 6.5 µg/ml STANDARD_DEVIATION 9.2 | 4.9 µg/ml STANDARD_DEVIATION 4.4 | 7.2 µg/ml STANDARD_DEVIATION 10.4 | 6.8 µg/ml STANDARD_DEVIATION 11.9 |
| Thromboxane B2 (TXB2) measured at baseline N=(53;20;23;93;30;30;90;31;30;67;467) | 3795.9 pg/mg Creatinine STANDARD_DEVIATION 2252.9 | 4705.6 pg/mg Creatinine STANDARD_DEVIATION 3047.5 | 4138.1 pg/mg Creatinine STANDARD_DEVIATION 2184.6 | 4485.7 pg/mg Creatinine STANDARD_DEVIATION 2147.8 | 4084.9 pg/mg Creatinine STANDARD_DEVIATION 2253.5 | 3619.0 pg/mg Creatinine STANDARD_DEVIATION 2020.6 | 4450.8 pg/mg Creatinine STANDARD_DEVIATION 2653.7 | 3735.6 pg/mg Creatinine STANDARD_DEVIATION 2440.6 | 3968.5 pg/mg Creatinine STANDARD_DEVIATION 2530.4 | 4177.9 pg/mg Creatinine STANDARD_DEVIATION 2661.2 | 4051.6 pg/mg Creatinine STANDARD_DEVIATION 2367.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 59 | 0 / 1 | 9 / 21 | 14 / 27 | 43 / 100 | 1 / 3 | 19 / 36 | 0 / 1 | 15 / 33 | 0 / 1 | 35 / 105 | 1 / 3 | 20 / 34 | 2 / 2 | 18 / 30 | 1 / 1 | 22 / 70 |
| serious Total, serious adverse events | 5 / 59 | 0 / 1 | 2 / 21 | 1 / 27 | 10 / 100 | 0 / 3 | 4 / 36 | 0 / 1 | 2 / 33 | 0 / 1 | 3 / 105 | 0 / 3 | 4 / 34 | 0 / 2 | 4 / 30 | 0 / 1 | 2 / 70 |
Outcome results
Primary
Number of Participants With Fatal or Life-threatening Major Bleeding Events
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
Population: All treated patients. No statistical comparisons were performed, due to the extremely small number of events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIBR 1048 50 mg b.i.d | Number of Participants With Fatal or Life-threatening Major Bleeding Events | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Fatal or Life-threatening Major Bleeding Events | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Fatal or Life-threatening Major Bleeding Events | 0 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Fatal or Life-threatening Major Bleeding Events | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Fatal or Life-threatening Major Bleeding Events | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Fatal or Life-threatening Major Bleeding Events | 0 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Fatal or Life-threatening Major Bleeding Events | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Fatal or Life-threatening Major Bleeding Events | 1 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Fatal or Life-threatening Major Bleeding Events | 3 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Fatal or Life-threatening Major Bleeding Events | 0 Participants |
Primary
Number of Participants With Minor/Nuisance Bleeding Events
All bleeding events not fulfilling one of the criteria for major bleeding event or minor/relevant bleeding events.
Time frame: 12 weeks
Population: All treated patients. No statistical comparisons were performed, due to the small number of events per group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIBR 1048 50 mg b.i.d | Number of Participants With Minor/Nuisance Bleeding Events | 2 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Minor/Nuisance Bleeding Events | 1 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Minor/Nuisance Bleeding Events | 2 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Minor/Nuisance Bleeding Events | 6 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Minor/Nuisance Bleeding Events | 6 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Minor/Nuisance Bleeding Events | 5 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Minor/Nuisance Bleeding Events | 9 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Minor/Nuisance Bleeding Events | 7 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Minor/Nuisance Bleeding Events | 9 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Minor/Nuisance Bleeding Events | 9 Participants |
Primary
Number of Participants With Minor/Relevant Bleeding Events
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
Population: All treated patients. No statistical comparisons were performed, due to the small number of events per group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIBR 1048 50 mg b.i.d | Number of Participants With Minor/Relevant Bleeding Events | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Minor/Relevant Bleeding Events | 1 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Minor/Relevant Bleeding Events | 1 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Minor/Relevant Bleeding Events | 9 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Minor/Relevant Bleeding Events | 2 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Minor/Relevant Bleeding Events | 2 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Minor/Relevant Bleeding Events | 6 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Minor/Relevant Bleeding Events | 4 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Minor/Relevant Bleeding Events | 3 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Minor/Relevant Bleeding Events | 4 Participants |
Secondary
11-dehydrothromboxane B2 (TXB2): Difference From Baseline
Difference from baseline to visit 7
Time frame: baseline and 12 weeks
Population: All treated patients. No statistical comparisons due to high variability
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIBR 1048 50 mg b.i.d | 11-dehydrothromboxane B2 (TXB2): Difference From Baseline | 596.5 pg/mg Creatinine | Standard Deviation 2896.3 |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | 11-dehydrothromboxane B2 (TXB2): Difference From Baseline | -1816.8 pg/mg Creatinine | Standard Deviation 2186.1 |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | 11-dehydrothromboxane B2 (TXB2): Difference From Baseline | -2779.8 pg/mg Creatinine | Standard Deviation 2953.3 |
| BIBR 1048 150 mg b.i.d | 11-dehydrothromboxane B2 (TXB2): Difference From Baseline | 922.0 pg/mg Creatinine | Standard Deviation 3874 |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | 11-dehydrothromboxane B2 (TXB2): Difference From Baseline | -1988.6 pg/mg Creatinine | Standard Deviation 2187.5 |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | 11-dehydrothromboxane B2 (TXB2): Difference From Baseline | -1125.9 pg/mg Creatinine | Standard Deviation 3566.6 |
| BIBR 1048 300 mg b.i.d | 11-dehydrothromboxane B2 (TXB2): Difference From Baseline | 1059.7 pg/mg Creatinine | Standard Deviation 2216.8 |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | 11-dehydrothromboxane B2 (TXB2): Difference From Baseline | -1822.6 pg/mg Creatinine | Standard Deviation 2381.7 |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | 11-dehydrothromboxane B2 (TXB2): Difference From Baseline | -1337.8 pg/mg Creatinine | Standard Deviation 2279.2 |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | 11-dehydrothromboxane B2 (TXB2): Difference From Baseline | 203.5 pg/mg Creatinine | Standard Deviation 2109 |
Secondary
Activated Partial Thromboplastin Time (aPTT): Difference From Baseline
Time frame: baseline and 12 weeks
Population: All treated patients. No statistical comparisons due to high variability
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIBR 1048 50 mg b.i.d | Activated Partial Thromboplastin Time (aPTT): Difference From Baseline | 6.4 seconds | Standard Deviation 5.6 |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Activated Partial Thromboplastin Time (aPTT): Difference From Baseline | 8.3 seconds | Standard Deviation 6.1 |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Activated Partial Thromboplastin Time (aPTT): Difference From Baseline | 8.8 seconds | Standard Deviation 9.4 |
| BIBR 1048 150 mg b.i.d | Activated Partial Thromboplastin Time (aPTT): Difference From Baseline | 13.5 seconds | Standard Deviation 18.3 |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Activated Partial Thromboplastin Time (aPTT): Difference From Baseline | 24.9 seconds | Standard Deviation 26.1 |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Activated Partial Thromboplastin Time (aPTT): Difference From Baseline | 14.5 seconds | Standard Deviation 11.5 |
| BIBR 1048 300 mg b.i.d | Activated Partial Thromboplastin Time (aPTT): Difference From Baseline | 25.0 seconds | Standard Deviation 12.4 |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Activated Partial Thromboplastin Time (aPTT): Difference From Baseline | 23.4 seconds | Standard Deviation 12.7 |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Activated Partial Thromboplastin Time (aPTT): Difference From Baseline | 27.2 seconds | Standard Deviation 24.2 |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Activated Partial Thromboplastin Time (aPTT): Difference From Baseline | 8.8 seconds | Standard Deviation 6.7 |
Secondary
D-dimer: Difference From Baseline
Difference in D-dimer from baseline to last available value
Time frame: baseline and 12 weeks
Population: All randomised patients, only per-protocol data included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIBR 1048 50 mg b.i.d | D-dimer: Difference From Baseline | 22.3 ng/ml | Standard Deviation 65.4 |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | D-dimer: Difference From Baseline | 12.3 ng/ml | Standard Deviation 25.3 |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | D-dimer: Difference From Baseline | 50.2 ng/ml | Standard Deviation 182.8 |
| BIBR 1048 150 mg b.i.d | D-dimer: Difference From Baseline | 8.1 ng/ml | Standard Deviation 41.6 |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | D-dimer: Difference From Baseline | 29.1 ng/ml | Standard Deviation 90.4 |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | D-dimer: Difference From Baseline | 8.6 ng/ml | Standard Deviation 49.2 |
| BIBR 1048 300 mg b.i.d | D-dimer: Difference From Baseline | 4.2 ng/ml | Standard Deviation 95.8 |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | D-dimer: Difference From Baseline | 11.3 ng/ml | Standard Deviation 82.2 |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | D-dimer: Difference From Baseline | -7.9 ng/ml | Standard Deviation 40.9 |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | D-dimer: Difference From Baseline | -5.8 ng/ml | Standard Deviation 50.6 |
Comparison: Group comparison of differences from baseline to last available valuep-value: 0.0357Kruskal-Wallis
Secondary
Ecarin Clotting Time (ECT): Difference From Baseline
Time frame: baseline and 12 weeks
Population: All treated patients. No statistical comparisons due to high variability
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIBR 1048 50 mg b.i.d | Ecarin Clotting Time (ECT): Difference From Baseline | 9.7 seconds | Standard Deviation 8.2 |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Ecarin Clotting Time (ECT): Difference From Baseline | 12.0 seconds | Standard Deviation 10.7 |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Ecarin Clotting Time (ECT): Difference From Baseline | 12.0 seconds | Standard Deviation 9.6 |
| BIBR 1048 150 mg b.i.d | Ecarin Clotting Time (ECT): Difference From Baseline | 31.9 seconds | Standard Deviation 26.2 |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Ecarin Clotting Time (ECT): Difference From Baseline | 42.5 seconds | Standard Deviation 29.2 |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Ecarin Clotting Time (ECT): Difference From Baseline | 32.7 seconds | Standard Deviation 23.1 |
| BIBR 1048 300 mg b.i.d | Ecarin Clotting Time (ECT): Difference From Baseline | 63.6 seconds | Standard Deviation 44.8 |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Ecarin Clotting Time (ECT): Difference From Baseline | 70.8 seconds | Standard Deviation 60.3 |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Ecarin Clotting Time (ECT): Difference From Baseline | 74.0 seconds | Standard Deviation 70.5 |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Ecarin Clotting Time (ECT): Difference From Baseline | 3.1 seconds | Standard Deviation 2.5 |
Secondary
Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline
Number of Participants with Increase of ALT to more than two times the baseline value
Time frame: 12 weeks
Population: All treated patients. No statistical comparisons due to extremely small number of cases
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBR 1048 50 mg b.i.d | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 50 mg b.i.d | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Yes | 3 Participants |
| BIBR 1048 50 mg b.i.d | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | No | 55 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | No | 18 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Yes | 2 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Yes | 1 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | No | 26 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Yes | 4 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | No | 95 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | No | 33 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Yes | 1 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | No | 32 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Yes | 1 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Missing | 1 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Yes | 4 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | No | 93 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | No | 31 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Missing | 1 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Yes | 1 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | No | 30 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Yes | 0 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Missing | 1 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | Yes | 5 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline | No | 64 Participants |
Secondary
Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline
Increase of AP to more than two times the baseline value
Time frame: 12 weeks
Population: All treated patients. No statistical comparisons due to extremely small number of cases
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBR 1048 50 mg b.i.d | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 50 mg b.i.d | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Yes | 0 Participants |
| BIBR 1048 50 mg b.i.d | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | No | 58 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | No | 20 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Yes | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Yes | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | No | 27 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Yes | 1 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | No | 98 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | No | 33 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Yes | 1 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | No | 33 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Yes | 0 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Missing | 1 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Yes | 0 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | No | 97 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | No | 32 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Missing | 1 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Yes | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | No | 29 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Yes | 1 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Missing | 1 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | Yes | 0 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline | No | 69 Participants |
Secondary
Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline
Increase of AST to more than two times the baseline value
Time frame: 12 weeks
Population: All treated patients. No statistical comparisons due to extremely small number of cases
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBR 1048 50 mg b.i.d | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 50 mg b.i.d | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Yes | 1 Participants |
| BIBR 1048 50 mg b.i.d | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | No | 57 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | No | 20 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Yes | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Yes | 3 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | No | 24 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Yes | 6 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | No | 93 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | No | 32 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Yes | 2 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | No | 31 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Yes | 2 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Missing | 1 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Yes | 2 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | No | 95 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | No | 31 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Missing | 1 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Yes | 1 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | No | 30 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Yes | 0 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Missing | 1 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | Yes | 1 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline | No | 68 Participants |
Secondary
Number of Participants With Increase of Bilirubin to >2*Baseline
Increase of Bilirubin to more than two times the baseline value
Time frame: 12 weeks
Population: All treated patients. No statistical comparisons due to extremely small number of cases
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBR 1048 50 mg b.i.d | Number of Participants With Increase of Bilirubin to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 50 mg b.i.d | Number of Participants With Increase of Bilirubin to >2*Baseline | Yes | 3 Participants |
| BIBR 1048 50 mg b.i.d | Number of Participants With Increase of Bilirubin to >2*Baseline | No | 55 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Increase of Bilirubin to >2*Baseline | No | 18 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Increase of Bilirubin to >2*Baseline | Yes | 2 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Increase of Bilirubin to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | Yes | 2 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | No | 25 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Increase of Bilirubin to >2*Baseline | Yes | 13 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Increase of Bilirubin to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Increase of Bilirubin to >2*Baseline | No | 86 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | No | 31 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | Yes | 3 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | No | 33 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | Yes | 0 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Increase of Bilirubin to >2*Baseline | Missing | 1 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Increase of Bilirubin to >2*Baseline | Yes | 9 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Increase of Bilirubin to >2*Baseline | No | 88 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | No | 29 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | Missing | 1 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | Yes | 3 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | No | 29 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | Missing | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Increase of Bilirubin to >2*Baseline | Yes | 1 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Increase of Bilirubin to >2*Baseline | Missing | 1 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Increase of Bilirubin to >2*Baseline | Yes | 6 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Increase of Bilirubin to >2*Baseline | No | 63 Participants |
Secondary
Number of Participants With Thromboembolic Events: Composite Endpoint
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
Population: All randomized patients. No statistical comparisons were performed, due to the extremely small number of events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIBR 1048 50 mg b.i.d | Number of Participants With Thromboembolic Events: Composite Endpoint | 1 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Thromboembolic Events: Composite Endpoint | 2 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Composite Endpoint | 1 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Thromboembolic Events: Composite Endpoint | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Thromboembolic Events: Composite Endpoint | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Composite Endpoint | 0 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Thromboembolic Events: Composite Endpoint | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Thromboembolic Events: Composite Endpoint | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Composite Endpoint | 0 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Thromboembolic Events: Composite Endpoint | 0 Participants |
Secondary
Number of Participants With Thromboembolic Events: Ischemic Stroke
Occurence of an ischemic stroke (fatal or non-fatal)
Time frame: 12 weeks
Population: All randomized patients. No statistical comparisons were performed, due to the extremely small number of events.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBR 1048 50 mg b.i.d | Number of Participants With Thromboembolic Events: Ischemic Stroke | None | 58 Participants |
| BIBR 1048 50 mg b.i.d | Number of Participants With Thromboembolic Events: Ischemic Stroke | Fatal | 0 Participants |
| BIBR 1048 50 mg b.i.d | Number of Participants With Thromboembolic Events: Ischemic Stroke | Non-Fatal | 0 Participants |
| BIBR 1048 50 mg b.i.d | Number of Participants With Thromboembolic Events: Ischemic Stroke | Both | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Thromboembolic Events: Ischemic Stroke | Fatal | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Thromboembolic Events: Ischemic Stroke | None | 19 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Thromboembolic Events: Ischemic Stroke | Both | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Number of Participants With Thromboembolic Events: Ischemic Stroke | Non-Fatal | 1 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Fatal | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | None | 27 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Non-Fatal | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Both | 0 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Thromboembolic Events: Ischemic Stroke | None | 99 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Thromboembolic Events: Ischemic Stroke | Fatal | 0 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Thromboembolic Events: Ischemic Stroke | Non-Fatal | 0 Participants |
| BIBR 1048 150 mg b.i.d | Number of Participants With Thromboembolic Events: Ischemic Stroke | Both | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Non-Fatal | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Fatal | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Both | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | None | 34 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Non-Fatal | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Fatal | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | None | 33 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Both | 0 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Thromboembolic Events: Ischemic Stroke | Fatal | 0 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Thromboembolic Events: Ischemic Stroke | Non-Fatal | 0 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Thromboembolic Events: Ischemic Stroke | Both | 0 Participants |
| BIBR 1048 300 mg b.i.d | Number of Participants With Thromboembolic Events: Ischemic Stroke | None | 98 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | None | 33 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Both | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Fatal | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Non-Fatal | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Both | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | None | 30 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Non-Fatal | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Number of Participants With Thromboembolic Events: Ischemic Stroke | Fatal | 0 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Thromboembolic Events: Ischemic Stroke | Non-Fatal | 0 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Thromboembolic Events: Ischemic Stroke | None | 70 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Thromboembolic Events: Ischemic Stroke | Both | 0 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Number of Participants With Thromboembolic Events: Ischemic Stroke | Fatal | 0 Participants |
Secondary
Severity of Adverse Events
Total number of patients with any adverse event of worst intensity 'mild', 'moderate' and 'severe'.
Time frame: 12 weeks
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBR 1048 50 mg b.i.d | Severity of Adverse Events | Mild | 24 participants |
| BIBR 1048 50 mg b.i.d | Severity of Adverse Events | Moderate | 13 participants |
| BIBR 1048 50 mg b.i.d | Severity of Adverse Events | Severe | 3 participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Severity of Adverse Events | Moderate | 0 participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Severity of Adverse Events | Mild | 0 participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Severity of Adverse Events | Severe | 0 participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Severity of Adverse Events | Mild | 9 participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Severity of Adverse Events | Severe | 1 participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Severity of Adverse Events | Moderate | 6 participants |
| BIBR 1048 150 mg b.i.d | Severity of Adverse Events | Severe | 1 participants |
| BIBR 1048 150 mg b.i.d | Severity of Adverse Events | Mild | 16 participants |
| BIBR 1048 150 mg b.i.d | Severity of Adverse Events | Moderate | 7 participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Severity of Adverse Events | Mild | 54 participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Severity of Adverse Events | Moderate | 19 participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Severity of Adverse Events | Severe | 4 participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Severity of Adverse Events | Severe | 0 participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Severity of Adverse Events | Moderate | 0 participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Severity of Adverse Events | Mild | 1 participants |
| BIBR 1048 300 mg b.i.d | Severity of Adverse Events | Moderate | 9 participants |
| BIBR 1048 300 mg b.i.d | Severity of Adverse Events | Mild | 23 participants |
| BIBR 1048 300 mg b.i.d | Severity of Adverse Events | Severe | 2 participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Severity of Adverse Events | Severe | 0 participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Severity of Adverse Events | Mild | 0 participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Severity of Adverse Events | Moderate | 0 participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Severity of Adverse Events | Moderate | 4 participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Severity of Adverse Events | Mild | 17 participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Severity of Adverse Events | Severe | 1 participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Severity of Adverse Events | Mild | 0 participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Severity of Adverse Events | Moderate | 0 participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Severity of Adverse Events | Severe | 0 participants |
| D300bid | Severity of Adverse Events | Moderate | 23 participants |
| D300bid | Severity of Adverse Events | Mild | 47 participants |
| D300bid | Severity of Adverse Events | Severe | 6 participants |
| D300qd | Severity of Adverse Events | Mild | 1 participants |
| D300qd | Severity of Adverse Events | Severe | 0 participants |
| D300qd | Severity of Adverse Events | Moderate | 0 participants |
| D300bid + ASA81qd | Severity of Adverse Events | Severe | 1 participants |
| D300bid + ASA81qd | Severity of Adverse Events | Moderate | 5 participants |
| D300bid + ASA81qd | Severity of Adverse Events | Mild | 23 participants |
| D300qd + ASA81qd | Severity of Adverse Events | Moderate | 1 participants |
| D300qd + ASA81qd | Severity of Adverse Events | Severe | 0 participants |
| D300qd + ASA81qd | Severity of Adverse Events | Mild | 2 participants |
| D300bid + ASA325qd | Severity of Adverse Events | Severe | 2 participants |
| D300bid + ASA325qd | Severity of Adverse Events | Moderate | 11 participants |
| D300bid + ASA325qd | Severity of Adverse Events | Mild | 23 participants |
| D300qd + ASA325qd | Severity of Adverse Events | Mild | 1 participants |
| D300qd + ASA325qd | Severity of Adverse Events | Severe | 0 participants |
| D300qd + ASA325qd | Severity of Adverse Events | Moderate | 1 participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Severity of Adverse Events | Severe | 2 participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Severity of Adverse Events | Mild | 30 participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Severity of Adverse Events | Moderate | 14 participants |
Secondary
Soluble Fibrin: Difference From Baseline
Difference from baseline to visit 7
Time frame: baseline and 12 weeks
Population: All randomised patients, only per-protocol data included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIBR 1048 50 mg b.i.d | Soluble Fibrin: Difference From Baseline | 3.2 µg/ml | Standard Deviation 22 |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Soluble Fibrin: Difference From Baseline | 0.9 µg/ml | Standard Deviation 2.3 |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Soluble Fibrin: Difference From Baseline | 1.2 µg/ml | Standard Deviation 8.4 |
| BIBR 1048 150 mg b.i.d | Soluble Fibrin: Difference From Baseline | 0.3 µg/ml | Standard Deviation 5.1 |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Soluble Fibrin: Difference From Baseline | -2.0 µg/ml | Standard Deviation 9.9 |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Soluble Fibrin: Difference From Baseline | -1.3 µg/ml | Standard Deviation 8.8 |
| BIBR 1048 300 mg b.i.d | Soluble Fibrin: Difference From Baseline | 2.3 µg/ml | Standard Deviation 26.8 |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Soluble Fibrin: Difference From Baseline | -0.7 µg/ml | Standard Deviation 4.6 |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Soluble Fibrin: Difference From Baseline | -1.9 µg/ml | Standard Deviation 12 |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Soluble Fibrin: Difference From Baseline | 0.1 µg/ml | Standard Deviation 4 |
Comparison: Group comparison of differences from baseline to week 12p-value: 0.26711Kruskal-Wallis
Secondary
Thromboembolic Events: Number of Participants Who Died
Occurence of death by all causes
Time frame: 12 weeks
Population: All randomized patients. No statistical comparisons were performed, due to the extremely small number of events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIBR 1048 50 mg b.i.d | Thromboembolic Events: Number of Participants Who Died | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Thromboembolic Events: Number of Participants Who Died | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants Who Died | 0 Participants |
| BIBR 1048 150 mg b.i.d | Thromboembolic Events: Number of Participants Who Died | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants Who Died | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants Who Died | 0 Participants |
| BIBR 1048 300 mg b.i.d | Thromboembolic Events: Number of Participants Who Died | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants Who Died | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants Who Died | 0 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Thromboembolic Events: Number of Participants Who Died | 0 Participants |
Secondary
Thromboembolic Events: Number of Participants With Myocardial Infarction
Occurence of a myocardial infarction
Time frame: 12 weeks
Population: All randomized patients. No statistical comparisons were performed, due to the extremely small number of events.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBR 1048 50 mg b.i.d | Thromboembolic Events: Number of Participants With Myocardial Infarction | None | 58 Participants |
| BIBR 1048 50 mg b.i.d | Thromboembolic Events: Number of Participants With Myocardial Infarction | Fatal | 0 Participants |
| BIBR 1048 50 mg b.i.d | Thromboembolic Events: Number of Participants With Myocardial Infarction | Non-Fatal | 0 Participants |
| BIBR 1048 50 mg b.i.d | Thromboembolic Events: Number of Participants With Myocardial Infarction | Both | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Thromboembolic Events: Number of Participants With Myocardial Infarction | Fatal | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Thromboembolic Events: Number of Participants With Myocardial Infarction | None | 20 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Thromboembolic Events: Number of Participants With Myocardial Infarction | Both | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Thromboembolic Events: Number of Participants With Myocardial Infarction | Non-Fatal | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Fatal | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | None | 27 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Non-Fatal | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Both | 0 Participants |
| BIBR 1048 150 mg b.i.d | Thromboembolic Events: Number of Participants With Myocardial Infarction | None | 99 Participants |
| BIBR 1048 150 mg b.i.d | Thromboembolic Events: Number of Participants With Myocardial Infarction | Fatal | 0 Participants |
| BIBR 1048 150 mg b.i.d | Thromboembolic Events: Number of Participants With Myocardial Infarction | Non-Fatal | 0 Participants |
| BIBR 1048 150 mg b.i.d | Thromboembolic Events: Number of Participants With Myocardial Infarction | Both | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Non-Fatal | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Fatal | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Both | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | None | 34 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Non-Fatal | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Fatal | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | None | 33 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Both | 0 Participants |
| BIBR 1048 300 mg b.i.d | Thromboembolic Events: Number of Participants With Myocardial Infarction | Fatal | 0 Participants |
| BIBR 1048 300 mg b.i.d | Thromboembolic Events: Number of Participants With Myocardial Infarction | Non-Fatal | 0 Participants |
| BIBR 1048 300 mg b.i.d | Thromboembolic Events: Number of Participants With Myocardial Infarction | Both | 0 Participants |
| BIBR 1048 300 mg b.i.d | Thromboembolic Events: Number of Participants With Myocardial Infarction | None | 98 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | None | 33 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Both | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Fatal | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Non-Fatal | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Both | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | None | 30 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Non-Fatal | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Myocardial Infarction | Fatal | 0 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Thromboembolic Events: Number of Participants With Myocardial Infarction | Non-Fatal | 0 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Thromboembolic Events: Number of Participants With Myocardial Infarction | None | 70 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Thromboembolic Events: Number of Participants With Myocardial Infarction | Both | 0 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Thromboembolic Events: Number of Participants With Myocardial Infarction | Fatal | 0 Participants |
Secondary
Thromboembolic Events: Number of Participants With Other Major Cardiac Events
Occurence of other major adverse cardiac events
Time frame: 12 weeks
Population: All randomized patients. No statistical comparisons were performed, due to the extremely small number of events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIBR 1048 50 mg b.i.d | Thromboembolic Events: Number of Participants With Other Major Cardiac Events | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Thromboembolic Events: Number of Participants With Other Major Cardiac Events | 1 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Other Major Cardiac Events | 1 Participants |
| BIBR 1048 150 mg b.i.d | Thromboembolic Events: Number of Participants With Other Major Cardiac Events | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants With Other Major Cardiac Events | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Other Major Cardiac Events | 0 Participants |
| BIBR 1048 300 mg b.i.d | Thromboembolic Events: Number of Participants With Other Major Cardiac Events | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants With Other Major Cardiac Events | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Other Major Cardiac Events | 0 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Thromboembolic Events: Number of Participants With Other Major Cardiac Events | 0 Participants |
Secondary
Thromboembolic Events: Number of Participants With Systemic Thromboembolism
Occurence of a systemic thromboembolism
Time frame: 12 weeks
Population: All randomized patients. No statistical comparisons were performed, due to the extremely small number of events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIBR 1048 50 mg b.i.d | Thromboembolic Events: Number of Participants With Systemic Thromboembolism | 1 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Thromboembolic Events: Number of Participants With Systemic Thromboembolism | 1 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Systemic Thromboembolism | 0 Participants |
| BIBR 1048 150 mg b.i.d | Thromboembolic Events: Number of Participants With Systemic Thromboembolism | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants With Systemic Thromboembolism | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Systemic Thromboembolism | 0 Participants |
| BIBR 1048 300 mg b.i.d | Thromboembolic Events: Number of Participants With Systemic Thromboembolism | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants With Systemic Thromboembolism | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Systemic Thromboembolism | 0 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Thromboembolic Events: Number of Participants With Systemic Thromboembolism | 0 Participants |
Secondary
Thromboembolic Events: Number of Participants With Transient Ischemic Attack
Occurence of a transient ischemic attack
Time frame: 12 weeks
Population: All randomized patients. No statistical comparisons were performed, due to the extremely small number of events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIBR 1048 50 mg b.i.d | Thromboembolic Events: Number of Participants With Transient Ischemic Attack | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Thromboembolic Events: Number of Participants With Transient Ischemic Attack | 0 Participants |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Transient Ischemic Attack | 0 Participants |
| BIBR 1048 150 mg b.i.d | Thromboembolic Events: Number of Participants With Transient Ischemic Attack | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants With Transient Ischemic Attack | 0 Participants |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Transient Ischemic Attack | 0 Participants |
| BIBR 1048 300 mg b.i.d | Thromboembolic Events: Number of Participants With Transient Ischemic Attack | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Thromboembolic Events: Number of Participants With Transient Ischemic Attack | 0 Participants |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Thromboembolic Events: Number of Participants With Transient Ischemic Attack | 0 Participants |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Thromboembolic Events: Number of Participants With Transient Ischemic Attack | 0 Participants |
Secondary
Trough Plasma Concentration of Dabigatran (BIBR 953)
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
Population: All treated patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIBR 1048 50 mg b.i.d | Trough Plasma Concentration of Dabigatran (BIBR 953) | 29.1 ng/ml | Standard Deviation 16.6 |
| BIBR 1048 50 mg b.i.d + ASA 81 mg q.d. | Trough Plasma Concentration of Dabigatran (BIBR 953) | 30.4 ng/ml | Standard Deviation 16.6 |
| BIBR 1048 50 mg b.i.d + ASA 325 mg qd | Trough Plasma Concentration of Dabigatran (BIBR 953) | 31.8 ng/ml | Standard Deviation 20 |
| BIBR 1048 150 mg b.i.d | Trough Plasma Concentration of Dabigatran (BIBR 953) | 82.8 ng/ml | Standard Deviation 54.3 |
| BIBR 1048 150 mg b.i.d + ASA 81 mg qd | Trough Plasma Concentration of Dabigatran (BIBR 953) | 103.2 ng/ml | Standard Deviation 69 |
| BIBR 1048 150 mg b.i.d + ASA 325 mg qd | Trough Plasma Concentration of Dabigatran (BIBR 953) | 90.1 ng/ml | Standard Deviation 52.5 |
| BIBR 1048 300 mg b.i.d | Trough Plasma Concentration of Dabigatran (BIBR 953) | 188.0 ng/ml | Standard Deviation 117.3 |
| BIBR 1048 300 mg b.i.d + ASA 81 mg qd | Trough Plasma Concentration of Dabigatran (BIBR 953) | 203.7 ng/ml | Standard Deviation 123.9 |
| BIBR 1048 300 mg b.i.d + ASA 325 mg qd | Trough Plasma Concentration of Dabigatran (BIBR 953) | 207.6 ng/ml | Standard Deviation 108.7 |
| Warfarin, Dosed to Target INR 2.0 to 3.0 | Trough Plasma Concentration of Dabigatran (BIBR 953) | NA ng/ml | — |