A Dose Response Study of Dabigatran Etexilate(BIBR 1048) in Pharmacodynamics and Safety in Patients With Non-valvular Atrial Fibrillation in Comparison to Warfarin
- Registration Number
- NCT01136408
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective was to evaluate the safety of dabigatran etexilate(BIBR 1048) administered orally at doses of 110 and 150 mg, twice daily, for 12 weeks in patients with non-valvular atrial fibrillation (paroxysmal, persistent or permanent) in comparison with warfarin.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 174
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dabigatran etexilate 220 mg daily Dabigatran etexilate Dabigatran etexilate 110 mg capsule, twice a day, oral administration Dabigatran etexilate 300 mg daily Dabigatran etexilate Dabigatran etexilate 150 mg capsule, twice a day, oral administration Warfarin Warfarin Dose-adjusted warfarin based on target INR values
- Primary Outcome Measures
Name Time Method Incidence and Severity of Adverse Events Upto 15 weeks Intensity of event is categorised as mild, moderate and severe.
Frequency (Occurrence Rates) of Major Bleeding Event upto 15 weeks The percentage of patients with major bleeding event.
Major bleeding was defined as any bleed fulfilling one of the following conditions:
* Fatal or life-threatening
* Retroperitoneal, intracranial, intraocular, or intraspinal bleeding (verified by objective testing)
* Bleeding requiring surgical treatment
* Clinically overt bleeding leading to a transfusion (erythrocyte component transfusion or whole blood transfusion) of 4.5 units (equal to 2 units in EU/US) or more
* Clinically overt bleeding leading to a fall in haemoglobin of at least 2 g/dLDiscontinuation of the Study Drug Due to Adverse Events Upto 15 weeks Discontinuation of the study drug due to adverse events.
Changes in Laboratory Test Values 12 weeks The number of patients with ALT, AST, alkaline phosphatase, or bilirubin exceeded the upper limit of normal (ULN) range
Frequency (Occurrence Rates) of Clinically Relevant Bleeding Event upto 15 weeks The percentage of patients with clinically relevant bleeding event.
Any bleed that did not qualify as a major bleed was defined as a minor bleed; minor bleed which fulfilled one of the criteria below was defined as a clinically relevant bleeding event:
* A skin haematoma of at least 25 sqcm
* Spontaneous nose bleed lasting for more than 5 minutes
* Macroscopic haematuria (either spontaneous or, if associated with an intervention, lasting more than 24 hours)
* Spontaneous rectal bleeding (more than spotting on toilet paper)
* Gingival bleeding lasting for more than 5 minutes
* Bleeding leading to hospitalisation
* Bleeding leading to blood transfusion (erythrocyte component transfusion or whole blood transfusion) of less than 4.5 units (equal to 2 units in EU/US)
* Any other bleeding considered clinically relevant by the investigatorFrequency (Occurrence Rates) of Nuisance Bleeding Event Upto 15 weeks The percentage of patients with nuisance bleeding event
Any bleed that did not qualify as a major bleed was defined as a minor bleed; all minor bleeding events not fulfilling one of the criteria below was defined as a nuisance bleeding event:
* A skin haematoma of at least 25 sqcm
* Spontaneous nose bleed lasting for more than 5 minutes
* Macroscopic haematuria (either spontaneous or, if associated with an intervention, lasting more than 24 hours)
* Spontaneous rectal bleeding (more than spotting on toilet paper)
* Gingival bleeding lasting for more than 5 minutes
* Bleeding leading to hospitalisation
* Bleeding leading to blood transfusion (erythrocyte component transfusion or whole blood transfusion) of less than 4.5 units (equal to 2 units in EU/US)
* Any other bleeding considered clinically relevant by the investigator
- Secondary Outcome Measures
Name Time Method Frequency (Occurrence Rates) of a Composite Clinical Endpoint. Upto 15 weeks Percentage of patients with the composite clinical endpoint (ischemic or haemorrhagic stroke (fatal or non-fatal), transient ischemic attacks, systemic embolism, myocardial infarction (fatal or non-fatal), other major adverse cardiac events, and death)
Frequency (Occurrence Rates) of Ischemic or Haemorrhagic Stroke (Fatal or Non-fatal) Upto 15 weeks The percentage of patients with ischemic or haemorrhagic stroke (fatal or non-fatal)
Frequency (Occurrence Rates) of Transient Ischemic Attack Upto 15 weeks The percentage of patients with transient ischemic attack
Frequency (Occurrence Rates) of Systemic Embolism Upto 15 weeks The percentage of patients with systemic embolism
Frequency (Occurrence Rates) of Myocardial Infarction (Fatal or Non-fatal) Upto 15 weeks The percentage of patients with myocardial infarction (fatal or non-fatal)
Frequency (Occurrence Rates) of Other Major Adverse Cardiac Events Upto 15 weeks The percentage of patients with other major adverse cardiac events
Frequency (Occurrence Rates) of Death Upto 15 weeks The percentage of patients with death
Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) Week 0,1,4 and 12 The blood coagulation parameter aPTT was assessed in patients allocated to the dabigatran etexilate groups at week 0, prior to drug administration and at the trough at week 1, 4 and 12.
Anticoagulation Effects Trough ECT (Ecarin Clotting Time) Week 0,1,4 and 12 The blood coagulation parameter ECT was assessed in patients allocated to the dabigatran etexilate groups at week 0, prior to drug administration and at the trough at week 1, 4 and 12.
Anticoagulation Effects Trough INR (International Normalised Ratio) Week 0,1,4 and 12 The blood coagulation parameter INR was assessed in patients allocated to the dabigatran etexilate groups at week 0, prior to drug administration and at the trough at week 1, 4 and 12.
Anticoagulation Effects Trough 11-dehydrothromboxane B2 Week 0 and 12 Analysis based on concomitant use of aspirin compared to no aspirin users. 11-dehydrothromboxane B2 is measured in urine of patients.
Steady-state Pharmacokinetics of Total Dabigatran Trough Plasma Concentration Week 1,4 and 12
Trial Locations
- Locations (28)
1160.49.014 Boehringer Ingelheim Investigational Site
🇯🇵Suita, Osaka, Japan
1160.49.027 Boehringer Ingelheim Investigational Site
🇯🇵Iizuka,Fukuoka, Japan
1160.49.013 Boehringer Ingelheim Investigational Site
🇯🇵Kyoto, Kyoto, Japan
1160.49.021 Boehringer Ingelheim Investigational Site
🇯🇵Himeji, Hyogo, Japan
1160.49.011 Boehringer Ingelheim Investigational Site
🇯🇵Nagoya, Aichi, Japan
1160.49.026 Boehringer Ingelheim Investigational Site
🇯🇵Fukuoka, Fukuoka, Japan
1160.49.019 Boehringer Ingelheim Investigational Site
🇯🇵Osaka, Osaka, Japan
1160.49.015 Boehringer Ingelheim Investigational Site
🇯🇵Suita, Osaka, Japan
1160.49.002 Boehringer Ingelheim Investigational Site
🇯🇵Sendai, Miyagi, Japan
1160.49.029 Nagano National Hospital
🇯🇵Ueda, Nagano, Japan
1160.49.024 Boehringer Ingelheim Investigational Site
🇯🇵Aki-gun, Hiroshima, Japan
1160.49.025 Boehringer Ingelheim Investigational Site
🇯🇵Fukuoka, Fukuoka, Japan
1160.49.004 Boehringer Ingelheim Investigational Site
🇯🇵Naka-gun, Ibaragi, Japan
1160.49.012 Boehringer Ingelheim Investigational Site
🇯🇵Nagoya, Aichi, Japan
1160.49.022 Boehringer Ingelheim Investigational Site
🇯🇵Okayama, Okayama, Japan
1160.49.006 Boehringer Ingelheim Investigational Site
🇯🇵Oota, Tokyo, Japan
1160.49.023 Boehringer Ingelheim Investigational Site
🇯🇵Okayama, Okayama, Japan
1160.49.018 Boehringer Ingelheim Investigational Site
🇯🇵Osaka, Osaka, Japan
1160.49.020 Boehringer Ingelheim Investigational Site
🇯🇵Sakai, Osaka, Japan
1160.49.017 Boehringer Ingelheim Investigational Site
🇯🇵Osaka, Osaka, Japan
1160.49.005 Boehringer Ingelheim Investigational Site
🇯🇵Shinjuku, Tokyo, Japan
1160.49.009 Boehringer Ingelheim Investigational Site
🇯🇵Toyama, Toyama, Japan
1160.49.001 Boehringer Ingelheim Investigational Site
🇯🇵Sapporo, Hokkaido, Japan
1160.49.028 Boehringer Ingelheim Investigational Site
🇯🇵Sapporo, Hokkaido, Japan
1160.49.003 Boehringer Ingelheim Investigational Site
🇯🇵Tsuchiura, Ibaragi, Japan
1160.49.008 Boehringer Ingelheim Investigational Site
🇯🇵Yokohama, Kanagawa, Japan
1160.49.007 Boehringer Ingelheim Investigational Site
🇯🇵Tokorozawa, Saitama, Japan
1160.49.016 Boehringer Ingelheim Investigational Site
🇯🇵Osaka, Osaka, Japan