Clinical trial 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
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atrial Fibrillation
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2010-06-03
Enrollment: 174
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Frequency (Occurrence Rates) of Major Bleeding Event
timeFrame: upto 15 weeks
measure: Frequency (Occurrence Rates) of Clinically Relevant Bleeding Event
timeFrame: upto 15 weeks
measure: Frequency (Occurrence Rates) of Nuisance Bleeding Event
timeFrame: Upto 15 weeks
measure: Incidence and Severity of Adverse Events
timeFrame: Upto 15 weeks
measure: Discontinuation of the Study Drug Due to Adverse Events
timeFrame: Upto 15 weeks
measure: Changes in Laboratory Test Values
timeFrame: 12 weeks
Secondary outcomes:
measure: Frequency (Occurrence Rates) of a Composite Clinical Endpoint.
timeFrame: Upto 15 weeks
measure: Frequency (Occurrence Rates) of Ischemic or Haemorrhagic Stroke (Fatal or Non-fatal)
timeFrame: Upto 15 weeks
measure: Frequency (Occurrence Rates) of Transient Ischemic Attack
timeFrame: Upto 15 weeks
measure: Frequency (Occurrence Rates) of Systemic Embolism
timeFrame: Upto 15 weeks
measure: Frequency (Occurrence Rates) of Myocardial Infarction (Fatal or Non-fatal)
timeFrame: Upto 15 weeks
measure: Frequency (Occurrence Rates) of Other Major Adverse Cardiac Events
timeFrame: Upto 15 weeks
measure: Frequency (Occurrence Rates) of Death
timeFrame: Upto 15 weeks
measure: Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time)
timeFrame: Week 0,1,4 and 12
measure: Anticoagulation Effects Trough ECT (Ecarin Clotting Time)
timeFrame: Week 0,1,4 and 12
measure: Anticoagulation Effects Trough INR (International Normalised Ratio)
timeFrame: Week 0,1,4 and 12
measure: Anticoagulation Effects Trough 11-dehydrothromboxane B2
timeFrame: Week 0 and 12
measure: Steady-state Pharmacokinetics of Total Dabigatran Trough Plasma Concentration
timeFrame: Week 1,4 and 12
Other outcomes:
Locations:
city: Aki-gun, Hiroshima
country: Japan
facility: 1160.49.024 Boehringer Ingelheim Investigational Site
city: Fukuoka, Fukuoka
country: Japan
facility: 1160.49.025 Boehringer Ingelheim Investigational Site
city: Fukuoka, Fukuoka
country: Japan
facility: 1160.49.026 Boehringer Ingelheim Investigational Site
city: Himeji, Hyogo
country: Japan
facility: 1160.49.021 Boehringer Ingelheim Investigational Site
city: Iizuka,Fukuoka
country: Japan
facility: 1160.49.027 Boehringer Ingelheim Investigational Site
city: Kyoto, Kyoto
country: Japan
facility: 1160.49.013 Boehringer Ingelheim Investigational Site
city: Nagoya, Aichi
country: Japan
facility: 1160.49.011 Boehringer Ingelheim Investigational Site
city: Nagoya, Aichi
country: Japan
facility: 1160.49.012 Boehringer Ingelheim Investigational Site
city: Naka-gun, Ibaragi
country: Japan
facility: 1160.49.004 Boehringer Ingelheim Investigational Site
city: Okayama, Okayama
country: Japan
facility: 1160.49.022 Boehringer Ingelheim Investigational Site
city: Okayama, Okayama
country: Japan
facility: 1160.49.023 Boehringer Ingelheim Investigational Site
city: Oota, Tokyo
country: Japan
facility: 1160.49.006 Boehringer Ingelheim Investigational Site
city: Osaka, Osaka
country: Japan
facility: 1160.49.016 Boehringer Ingelheim Investigational Site
city: Osaka, Osaka
country: Japan
facility: 1160.49.017 Boehringer Ingelheim Investigational Site
city: Osaka, Osaka
country: Japan
facility: 1160.49.018 Boehringer Ingelheim Investigational Site
city: Osaka, Osaka
country: Japan
facility: 1160.49.019 Boehringer Ingelheim Investigational Site
city: Sakai, Osaka
country: Japan
facility: 1160.49.020 Boehringer Ingelheim Investigational Site
city: Sapporo, Hokkaido
country: Japan
facility: 1160.49.001 Boehringer Ingelheim Investigational Site
city: Sapporo, Hokkaido
country: Japan
facility: 1160.49.028 Boehringer Ingelheim Investigational Site
city: Sendai, Miyagi
country: Japan
facility: 1160.49.002 Boehringer Ingelheim Investigational Site
city: Shinjuku, Tokyo
country: Japan
facility: 1160.49.005 Boehringer Ingelheim Investigational Site
city: Suita, Osaka
country: Japan
facility: 1160.49.014 Boehringer Ingelheim Investigational Site
city: Suita, Osaka
country: Japan
facility: 1160.49.015 Boehringer Ingelheim Investigational Site
city: Tokorozawa, Saitama
country: Japan
facility: 1160.49.007 Boehringer Ingelheim Investigational Site
city: Toyama, Toyama
country: Japan
facility: 1160.49.009 Boehringer Ingelheim Investigational Site
city: Tsuchiura, Ibaragi
country: Japan
facility: 1160.49.003 Boehringer Ingelheim Investigational Site
city: Ueda, Nagano
country: Japan
facility: 1160.49.029 Nagano National Hospital
city: Yokohama, Kanagawa
country: Japan
facility: 1160.49.008 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: