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Completed

NCT Number: NCT01136408

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

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.

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Key information

Conditions

Atrial Fibrillation Arrhythmias, Cardiac Cardiovascular Diseases Heart Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

1160.49.024 Boehringer Ingelheim Investigational Site, Aki-gun, Hiroshima, Japan

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Dabigatran Etexilate

Drug

Dabigatran etexilate 110 mg capsule, twice a day, oral administration

Warfarin

Drug

Dose-adjusted warfarin based on target INR values

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. Incidence and Severity of Adverse Events

    Time frame: Upto 15 weeks

    Intensity of event is categorised as mild, moderate and severe.

  5. Discontinuation of the Study Drug Due to Adverse Events

    Time frame: Upto 15 weeks

    Discontinuation of the study drug due to adverse events.

  6. 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

Secondary outcomes

  1. 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)

  2. 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)

  3. Frequency (Occurrence Rates) of Transient Ischemic Attack

    Time frame: Upto 15 weeks

    The percentage of patients with transient ischemic attack

  4. Frequency (Occurrence Rates) of Systemic Embolism

    Time frame: Upto 15 weeks

    The percentage of patients with systemic embolism

  5. 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)

  6. Frequency (Occurrence Rates) of Other Major Adverse Cardiac Events

    Time frame: Upto 15 weeks

    The percentage of patients with other major adverse cardiac events

  7. Frequency (Occurrence Rates) of Death

    Time frame: Upto 15 weeks

    The percentage of patients with death

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Steady-state Pharmacokinetics of Total Dabigatran Trough Plasma Concentration

    Time frame: Week 1,4 and 12

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study 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

Important dates

Study start
2005
Primary completion
2006
First posted
Jun 3, 2010
Registry last updated
Mar 19, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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