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A Dose Response Study of Dabigatran Etexilate(BIBR 1048) in Pharmacodynamics and Safety in Patients With Non-valvular Atrial Fibrillation in Comparison to Warfarin

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ClinicalTrials.gov Identifier: NCT01136408
Recruitment Status : Completed
First Posted : June 3, 2010
Results First Posted : December 17, 2010
Last Update Posted : March 19, 2014
Sponsor:
Information provided by:
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE May 19, 2010
First Posted Date  ICMJE June 3, 2010
Results First Submitted Date  ICMJE November 18, 2010
Results First Posted Date  ICMJE December 17, 2010
Last Update Posted Date March 19, 2014
Study Start Date  ICMJE November 2005
Actual Primary Completion Date September 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 18, 2014)
  • Frequency (Occurrence Rates) of Major Bleeding Event [ Time Frame: 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/dL
  • Frequency (Occurrence Rates) of Clinically Relevant Bleeding Event [ Time Frame: 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 investigator
  • Frequency (Occurrence Rates) of Nuisance Bleeding Event [ Time Frame: 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
  • Incidence and Severity of Adverse Events [ Time Frame: Upto 15 weeks ]
    Intensity of event is categorised as mild, moderate and severe.
  • Discontinuation of the Study Drug Due to Adverse Events [ Time Frame: Upto 15 weeks ]
    Discontinuation of the study drug due to adverse events.
  • Changes in Laboratory Test Values [ Time Frame: 12 weeks ]
    The number of patients with ALT, AST, alkaline phosphatase, or bilirubin exceeded the upper limit of normal (ULN) range
Original Primary Outcome Measures  ICMJE
 (submitted: June 2, 2010)
  • Incidence of Major Bleeding Event [ Time Frame: Treatment period: from the first dose of study medication and ending 6 days after the last dose of study medication ]
  • Incidence of Clinically Relevant Bleeding Event [ Time Frame: Treatment period: from the first dose of study medication and ending 6 days after the last dose of study medication ]
  • Incidence of Nuisance Bleeding Event [ Time Frame: Treatment period: from the first dose of study medication and ending 6 days after the last dose of study medication ]
Change History Complete list of historical versions of study NCT01136408 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2014)
  • Frequency (Occurrence Rates) of a Composite Clinical Endpoint. [ Time Frame: 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) [ Time Frame: Upto 15 weeks ]
    The percentage of patients with ischemic or haemorrhagic stroke (fatal or non-fatal)
  • Frequency (Occurrence Rates) of Transient Ischemic Attack [ Time Frame: Upto 15 weeks ]
    The percentage of patients with transient ischemic attack
  • Frequency (Occurrence Rates) of Systemic Embolism [ Time Frame: Upto 15 weeks ]
    The percentage of patients with systemic embolism
  • Frequency (Occurrence Rates) of Myocardial Infarction (Fatal or Non-fatal) [ Time Frame: Upto 15 weeks ]
    The percentage of patients with myocardial infarction (fatal or non-fatal)
  • Frequency (Occurrence Rates) of Other Major Adverse Cardiac Events [ Time Frame: Upto 15 weeks ]
    The percentage of patients with other major adverse cardiac events
  • Frequency (Occurrence Rates) of Death [ Time Frame: Upto 15 weeks ]
    The percentage of patients with death
  • Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Week 1,4 and 12 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 2, 2010)
  • A Composite Clinical Endpoint Including the Incidence of 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: Treatment period: from the first dose of study medication and ending 6 days after the last dose of study medication ]
  • The Incidence of Ischemic or Haemorrhagic Stroke (Fatal or Non-fatal) [ Time Frame: Treatment period: from the first dose of study medication and ending 6 days after the last dose of study medication ]
  • The Incidence of Transient Ischemic Attack [ Time Frame: Treatment period: from the first dose of study medication and ending 6 days after the last dose of study medication ]
  • The Incidence of Systemic Embolism [ Time Frame: Treatment period: from the first dose of study medication and ending 6 days after the last dose of study medication ]
  • The Incidence of Myocardial Infarction (Fatal or Non-fatal) [ Time Frame: Treatment period: from the first dose of study medication and ending 6 days after the last dose of study medication ]
  • The Incidence of Other Major Adverse Cardiac Events [ Time Frame: Treatment period: from the first dose of study medication and ending 6 days after the last dose of study medication ]
  • The Incidence of Death [ Time Frame: Treatment period: from the first dose of study medication and ending 6 days after the last dose of study medication ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Atrial Fibrillation
Intervention  ICMJE
  • Drug: Dabigatran etexilate
    Dabigatran etexilate 110 mg capsule, twice a day, oral administration
  • Drug: Dabigatran etexilate
    Dabigatran etexilate 150 mg capsule, twice a day, oral administration
  • Drug: Warfarin
    Dose-adjusted warfarin based on target INR values
Study Arms  ICMJE
  • Experimental: Dabigatran etexilate 220 mg daily
    Dabigatran etexilate 110 mg capsule, twice a day, oral administration
    Intervention: Drug: Dabigatran etexilate
  • Experimental: Dabigatran etexilate 300 mg daily
    Dabigatran etexilate 150 mg capsule, twice a day, oral administration
    Intervention: Drug: Dabigatran etexilate
  • Active Comparator: Warfarin
    Dose-adjusted warfarin based on target INR values
    Intervention: Drug: Warfarin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 2, 2010)
174
Original Actual Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date September 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria Inclusion criteria

  1. Patients with non-valvular atrial fibrillation (paroxysmal, persistent or permanent)
  2. 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

  1. Patients diagnosed as having a valvular heart disease by echocardiography, or patients who had a history of prosthetic valve replacement or valve surgery
  2. Patients who were to receive electric defibrillation or pharmacological defibrillation during the study period
  3. Patients who developed stroke or transient ischemic attack within 30 days before the date of informed consent
  4. 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
  5. Patients with atrial myxoma or left ventricular thrombosis
  6. Patients with contraindication to anticoagulant therapies
  7. Patients scheduled for major surgery or invasive procedure
  8. Patients having major bleeding from non-gastrointestinal organs within 6 months before the date of informed consent
  9. Patients with uncontrolled hypertension
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01136408
Other Study ID Numbers  ICMJE 1160.49
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account Boehringer Ingelheim
Verification Date February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP