Back to resultsA Dose Response Study of Dabigatran Etexilate(BIBR 1048) in Pharmacodynamics and Safety in Patients With Non-valvular Atrial Fibrillation in Comparison to Warfarin
Primary Purpose
Atrial Fibrillation
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Dabigatran etexilate
Dabigatran etexilate
Warfarin
Sponsored by
About this trial
This is an interventional prevention trial for Atrial Fibrillation
Eligibility Criteria
Inclusion criteria Inclusion criteria
- Patients with non-valvular atrial fibrillation (paroxysmal, persistent or permanent)
Patients who had additional risk factor for thromboembolism; one or more of the following conditions/events:
- Hypertension
- Diabetes mellitus
- Left-side heart failure
- A previous ischemic stroke or transient ischemic attack
- Age 75 years or older
- A history of coronary artery diseases
Exclusion criteria Exclusion criteria
- Patients diagnosed as having a valvular heart disease by echocardiography, or patients who had a history of prosthetic valve replacement or valve surgery
- Patients who were to receive electric defibrillation or pharmacological defibrillation during the study period
- Patients who developed stroke or transient ischemic attack within 30 days before the date of informed consent
- Patients who developed myocardial infarction or were admitted to hospital due to acute coronary syndrome or for percutaneous transluminal coronary angioplasty within 3 months before the date of informed consent or patients underwent coronary stenting within 6 months before the date of informed consent
- Patients with atrial myxoma or left ventricular thrombosis
- Patients with contraindication to anticoagulant therapies
- Patients scheduled for major surgery or invasive procedure
- Patients having major bleeding from non-gastrointestinal organs within 6 months before the date of informed consent
- Patients with uncontrolled hypertension
Sites / Locations
- 1160.49.024 Boehringer Ingelheim Investigational Site
- 1160.49.025 Boehringer Ingelheim Investigational Site
- 1160.49.026 Boehringer Ingelheim Investigational Site
- 1160.49.021 Boehringer Ingelheim Investigational Site
- 1160.49.027 Boehringer Ingelheim Investigational Site
- 1160.49.013 Boehringer Ingelheim Investigational Site
- 1160.49.011 Boehringer Ingelheim Investigational Site
- 1160.49.012 Boehringer Ingelheim Investigational Site
- 1160.49.004 Boehringer Ingelheim Investigational Site
- 1160.49.022 Boehringer Ingelheim Investigational Site
- 1160.49.023 Boehringer Ingelheim Investigational Site
- 1160.49.006 Boehringer Ingelheim Investigational Site
- 1160.49.016 Boehringer Ingelheim Investigational Site
- 1160.49.017 Boehringer Ingelheim Investigational Site
- 1160.49.018 Boehringer Ingelheim Investigational Site
- 1160.49.019 Boehringer Ingelheim Investigational Site
- 1160.49.020 Boehringer Ingelheim Investigational Site
- 1160.49.001 Boehringer Ingelheim Investigational Site
- 1160.49.028 Boehringer Ingelheim Investigational Site
- 1160.49.002 Boehringer Ingelheim Investigational Site
- 1160.49.005 Boehringer Ingelheim Investigational Site
- 1160.49.014 Boehringer Ingelheim Investigational Site
- 1160.49.015 Boehringer Ingelheim Investigational Site
- 1160.49.007 Boehringer Ingelheim Investigational Site
- 1160.49.009 Boehringer Ingelheim Investigational Site
- 1160.49.003 Boehringer Ingelheim Investigational Site
- 1160.49.029 Nagano National Hospital
- 1160.49.008 Boehringer Ingelheim Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Dabigatran etexilate 220 mg daily
Dabigatran etexilate 300 mg daily
Warfarin
Arm Description
Dabigatran etexilate 110 mg capsule, twice a day, oral administration
Dabigatran etexilate 150 mg capsule, twice a day, oral administration
Dose-adjusted warfarin based on target INR values
Outcomes
Primary Outcome Measures
Frequency (Occurrence Rates) of Major Bleeding Event
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/dL
Frequency (Occurrence Rates) of Clinically Relevant Bleeding Event
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 investigator
Frequency (Occurrence Rates) of Nuisance Bleeding Event
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
Incidence and Severity of Adverse Events
Intensity of event is categorised as mild, moderate and severe.
Discontinuation of the Study Drug Due to Adverse Events
Discontinuation of the study drug due to adverse events.
Changes in Laboratory Test Values
The number of patients with ALT, AST, alkaline phosphatase, or bilirubin exceeded the upper limit of normal (ULN) range
Secondary Outcome Measures
Frequency (Occurrence Rates) of a Composite Clinical Endpoint.
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)
The percentage of patients with ischemic or haemorrhagic stroke (fatal or non-fatal)
Frequency (Occurrence Rates) of Transient Ischemic Attack
The percentage of patients with transient ischemic attack
Frequency (Occurrence Rates) of Systemic Embolism
The percentage of patients with systemic embolism
Frequency (Occurrence Rates) of Myocardial Infarction (Fatal or Non-fatal)
The percentage of patients with myocardial infarction (fatal or non-fatal)
Frequency (Occurrence Rates) of Other Major Adverse Cardiac Events
The percentage of patients with other major adverse cardiac events
Frequency (Occurrence Rates) of Death
The percentage of patients with death
Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time)
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)
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)
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01136408
Brief Title
A Dose Response Study of Dabigatran Etexilate(BIBR 1048) in Pharmacodynamics and Safety in Patients With Non-valvular Atrial Fibrillation in Comparison to Warfarin
Official Title
Open Label, Randomised Exploratory Dose Response Study in Pharmacodynamics and Safety of BIBR 1048 (110 mg Twice Daily (b.i.d.) and 150 mg b.i.d.) for 12 Weeks in Patients With Non-valvular Atrial Fibrillation in Comparison to Warfarin
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
November 2005 (undefined)
Primary Completion Date
September 2006 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
174 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dabigatran etexilate 220 mg daily
Arm Type
Experimental
Arm Description
Dabigatran etexilate 110 mg capsule, twice a day, oral administration
Arm Title
Dabigatran etexilate 300 mg daily
Arm Type
Experimental
Arm Description
Dabigatran etexilate 150 mg capsule, twice a day, oral administration
Arm Title
Warfarin
Arm Type
Active Comparator
Arm Description
Dose-adjusted warfarin based on target INR values
Intervention Type
Drug
Intervention Name(s)
Dabigatran etexilate
Intervention Description
Dabigatran etexilate 110 mg capsule, twice a day, oral administration
Intervention Type
Drug
Intervention Name(s)
Dabigatran etexilate
Intervention Description
Dabigatran etexilate 150 mg capsule, twice a day, oral administration
Intervention Type
Drug
Intervention Name(s)
Warfarin
Intervention Description
Dose-adjusted warfarin based on target INR values
Primary Outcome Measure Information:
Title
Frequency (Occurrence Rates) of Major Bleeding Event
Description
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/dL
Time Frame
upto 15 weeks
Title
Frequency (Occurrence Rates) of Clinically Relevant Bleeding Event
Description
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 investigator
Time Frame
upto 15 weeks
Title
Frequency (Occurrence Rates) of Nuisance Bleeding Event
Description
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
Time Frame
Upto 15 weeks
Title
Incidence and Severity of Adverse Events
Description
Intensity of event is categorised as mild, moderate and severe.
Time Frame
Upto 15 weeks
Title
Discontinuation of the Study Drug Due to Adverse Events
Description
Discontinuation of the study drug due to adverse events.
Time Frame
Upto 15 weeks
Title
Changes in Laboratory Test Values
Description
The number of patients with ALT, AST, alkaline phosphatase, or bilirubin exceeded the upper limit of normal (ULN) range
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Frequency (Occurrence Rates) of a Composite Clinical Endpoint.
Description
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)
Time Frame
Upto 15 weeks
Title
Frequency (Occurrence Rates) of Ischemic or Haemorrhagic Stroke (Fatal or Non-fatal)
Description
The percentage of patients with ischemic or haemorrhagic stroke (fatal or non-fatal)
Time Frame
Upto 15 weeks
Title
Frequency (Occurrence Rates) of Transient Ischemic Attack
Description
The percentage of patients with transient ischemic attack
Time Frame
Upto 15 weeks
Title
Frequency (Occurrence Rates) of Systemic Embolism
Description
The percentage of patients with systemic embolism
Time Frame
Upto 15 weeks
Title
Frequency (Occurrence Rates) of Myocardial Infarction (Fatal or Non-fatal)
Description
The percentage of patients with myocardial infarction (fatal or non-fatal)
Time Frame
Upto 15 weeks
Title
Frequency (Occurrence Rates) of Other Major Adverse Cardiac Events
Description
The percentage of patients with other major adverse cardiac events
Time Frame
Upto 15 weeks
Title
Frequency (Occurrence Rates) of Death
Description
The percentage of patients with death
Time Frame
Upto 15 weeks
Title
Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time)
Description
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.
Time Frame
Week 0,1,4 and 12
Title
Anticoagulation Effects Trough ECT (Ecarin Clotting Time)
Description
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.
Time Frame
Week 0,1,4 and 12
Title
Anticoagulation Effects Trough INR (International Normalised Ratio)
Description
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.
Time Frame
Week 0,1,4 and 12
Title
Anticoagulation Effects Trough 11-dehydrothromboxane B2
Description
Analysis based on concomitant use of aspirin compared to no aspirin users. 11-dehydrothromboxane B2 is measured in urine of patients.
Time Frame
Week 0 and 12
Title
Steady-state Pharmacokinetics of Total Dabigatran Trough Plasma Concentration
Time Frame
Week 1,4 and 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria Inclusion criteria
Patients with non-valvular atrial fibrillation (paroxysmal, persistent or permanent)
Patients who had additional risk factor for thromboembolism; one or more of the following conditions/events:
Hypertension
Diabetes mellitus
Left-side heart failure
A previous ischemic stroke or transient ischemic attack
Age 75 years or older
A history of coronary artery diseases
Exclusion criteria Exclusion criteria
Patients diagnosed as having a valvular heart disease by echocardiography, or patients who had a history of prosthetic valve replacement or valve surgery
Patients who were to receive electric defibrillation or pharmacological defibrillation during the study period
Patients who developed stroke or transient ischemic attack within 30 days before the date of informed consent
Patients who developed myocardial infarction or were admitted to hospital due to acute coronary syndrome or for percutaneous transluminal coronary angioplasty within 3 months before the date of informed consent or patients underwent coronary stenting within 6 months before the date of informed consent
Patients with atrial myxoma or left ventricular thrombosis
Patients with contraindication to anticoagulant therapies
Patients scheduled for major surgery or invasive procedure
Patients having major bleeding from non-gastrointestinal organs within 6 months before the date of informed consent
Patients with uncontrolled hypertension
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
1160.49.024 Boehringer Ingelheim Investigational Site
City
Aki-gun, Hiroshima
Country
Japan
Facility Name
1160.49.025 Boehringer Ingelheim Investigational Site
City
Fukuoka, Fukuoka
Country
Japan
Facility Name
1160.49.026 Boehringer Ingelheim Investigational Site
City
Fukuoka, Fukuoka
Country
Japan
Facility Name
1160.49.021 Boehringer Ingelheim Investigational Site
City
Himeji, Hyogo
Country
Japan
Facility Name
1160.49.027 Boehringer Ingelheim Investigational Site
City
Iizuka,Fukuoka
Country
Japan
Facility Name
1160.49.013 Boehringer Ingelheim Investigational Site
City
Kyoto, Kyoto
Country
Japan
Facility Name
1160.49.011 Boehringer Ingelheim Investigational Site
City
Nagoya, Aichi
Country
Japan
Facility Name
1160.49.012 Boehringer Ingelheim Investigational Site
City
Nagoya, Aichi
Country
Japan
Facility Name
1160.49.004 Boehringer Ingelheim Investigational Site
City
Naka-gun, Ibaragi
Country
Japan
Facility Name
1160.49.022 Boehringer Ingelheim Investigational Site
City
Okayama, Okayama
Country
Japan
Facility Name
1160.49.023 Boehringer Ingelheim Investigational Site
City
Okayama, Okayama
Country
Japan
Facility Name
1160.49.006 Boehringer Ingelheim Investigational Site
City
Oota, Tokyo
Country
Japan
Facility Name
1160.49.016 Boehringer Ingelheim Investigational Site
City
Osaka, Osaka
Country
Japan
Facility Name
1160.49.017 Boehringer Ingelheim Investigational Site
City
Osaka, Osaka
Country
Japan
Facility Name
1160.49.018 Boehringer Ingelheim Investigational Site
City
Osaka, Osaka
Country
Japan
Facility Name
1160.49.019 Boehringer Ingelheim Investigational Site
City
Osaka, Osaka
Country
Japan
Facility Name
1160.49.020 Boehringer Ingelheim Investigational Site
City
Sakai, Osaka
Country
Japan
Facility Name
1160.49.001 Boehringer Ingelheim Investigational Site
City
Sapporo, Hokkaido
Country
Japan
Facility Name
1160.49.028 Boehringer Ingelheim Investigational Site
City
Sapporo, Hokkaido
Country
Japan
Facility Name
1160.49.002 Boehringer Ingelheim Investigational Site
City
Sendai, Miyagi
Country
Japan
Facility Name
1160.49.005 Boehringer Ingelheim Investigational Site
City
Shinjuku, Tokyo
Country
Japan
Facility Name
1160.49.014 Boehringer Ingelheim Investigational Site
City
Suita, Osaka
Country
Japan
Facility Name
1160.49.015 Boehringer Ingelheim Investigational Site
City
Suita, Osaka
Country
Japan
Facility Name
1160.49.007 Boehringer Ingelheim Investigational Site
City
Tokorozawa, Saitama
Country
Japan
Facility Name
1160.49.009 Boehringer Ingelheim Investigational Site
City
Toyama, Toyama
Country
Japan
Facility Name
1160.49.003 Boehringer Ingelheim Investigational Site
City
Tsuchiura, Ibaragi
Country
Japan
Facility Name
1160.49.029 Nagano National Hospital
City
Ueda, Nagano
Country
Japan
Facility Name
1160.49.008 Boehringer Ingelheim Investigational Site
City
Yokohama, Kanagawa
Country
Japan
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1160/1160.49_U07-3126.pdf
Description
Related Info
Learn more about this trial
A Dose Response Study of Dabigatran Etexilate(BIBR 1048) in Pharmacodynamics and Safety in Patients With Non-valvular Atrial Fibrillation in Comparison to Warfarin
We'll reach out to this number within 24 hrs