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

NCT01136408 | Completed Phase 2 Results

• 1 other identifier: 1160.49
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 28

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.

Conditions

Atrial Fibrillation

Outcome Measures

Primary Outcomes (6)

• 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

  upto 15 weeks

• 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

  upto 15 weeks

• 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

  Upto 15 weeks

• Incidence and Severity of Adverse Events

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

  Upto 15 weeks

• Discontinuation of the Study Drug Due to Adverse Events

  Discontinuation of the study drug due to adverse events.

  Upto 15 weeks

• Changes in Laboratory Test Values

  The number of patients with ALT, AST, alkaline phosphatase, or bilirubin exceeded the upper limit of normal (ULN) range

  12 weeks

Secondary Outcomes (12)

• Frequency (Occurrence Rates) of a Composite Clinical Endpoint.

  Upto 15 weeks

• Frequency (Occurrence Rates) of Ischemic or Haemorrhagic Stroke (Fatal or Non-fatal)

  Upto 15 weeks

• Frequency (Occurrence Rates) of Transient Ischemic Attack

  Upto 15 weeks

• Frequency (Occurrence Rates) of Systemic Embolism

  Upto 15 weeks

• Frequency (Occurrence Rates) of Myocardial Infarction (Fatal or Non-fatal)

  Upto 15 weeks

Study Arms (3)

Dabigatran etexilate 220 mg daily

EXPERIMENTAL

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

Drug: Dabigatran etexilate

Dabigatran etexilate 300 mg daily

EXPERIMENTAL

Dabigatran etexilate 150 mg capsule, twice a day, oral administration

Drug: Dabigatran etexilate

Warfarin

ACTIVE COMPARATOR

Dose-adjusted warfarin based on target INR values

Drug: Warfarin

Interventions

Dabigatran etexilate DRUG

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

Dabigatran etexilate 220 mg daily

Warfarin DRUG

Dose-adjusted warfarin based on target INR values

Warfarin

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (28)

1160.49.024 Boehringer Ingelheim Investigational Site

Aki-gun, Hiroshima, Japan

Location

1160.49.025 Boehringer Ingelheim Investigational Site

Fukuoka, Fukuoka, Japan

Location

1160.49.026 Boehringer Ingelheim Investigational Site

Fukuoka, Fukuoka, Japan

Location

1160.49.021 Boehringer Ingelheim Investigational Site

Himeji, Hyogo, Japan

Location

1160.49.027 Boehringer Ingelheim Investigational Site

Iizuka,Fukuoka, Japan

Location

1160.49.013 Boehringer Ingelheim Investigational Site

Kyoto, Kyoto, Japan

Location

1160.49.011 Boehringer Ingelheim Investigational Site

Nagoya, Aichi, Japan

Location

1160.49.012 Boehringer Ingelheim Investigational Site

Nagoya, Aichi, Japan

Location

1160.49.004 Boehringer Ingelheim Investigational Site

Naka-gun, Ibaragi, Japan

Location

1160.49.022 Boehringer Ingelheim Investigational Site

Okayama, Okayama, Japan

Location

1160.49.023 Boehringer Ingelheim Investigational Site

Okayama, Okayama, Japan

Location

1160.49.006 Boehringer Ingelheim Investigational Site

Oota, Tokyo, Japan

Location

1160.49.016 Boehringer Ingelheim Investigational Site

Osaka, Osaka, Japan

Location

1160.49.017 Boehringer Ingelheim Investigational Site

Osaka, Osaka, Japan

Location

1160.49.018 Boehringer Ingelheim Investigational Site

Osaka, Osaka, Japan

Location

1160.49.019 Boehringer Ingelheim Investigational Site

Osaka, Osaka, Japan

Location

1160.49.020 Boehringer Ingelheim Investigational Site

Sakai, Osaka, Japan

Location

1160.49.001 Boehringer Ingelheim Investigational Site

Sapporo, Hokkaido, Japan

Location

1160.49.028 Boehringer Ingelheim Investigational Site

Sapporo, Hokkaido, Japan

Location

1160.49.002 Boehringer Ingelheim Investigational Site

Sendai, Miyagi, Japan

Location

1160.49.005 Boehringer Ingelheim Investigational Site

Shinjuku, Tokyo, Japan

Location

1160.49.014 Boehringer Ingelheim Investigational Site

Suita, Osaka, Japan

Location

1160.49.015 Boehringer Ingelheim Investigational Site

Suita, Osaka, Japan

Location

1160.49.007 Boehringer Ingelheim Investigational Site

Tokorozawa, Saitama, Japan

Location

1160.49.009 Boehringer Ingelheim Investigational Site

Toyama, Toyama, Japan

Location

1160.49.003 Boehringer Ingelheim Investigational Site

Tsuchiura, Ibaragi, Japan

Location

1160.49.029 Nagano National Hospital

Ueda, Nagano, Japan

Location

1160.49.008 Boehringer Ingelheim Investigational Site

Yokohama, Kanagawa, Japan

Location

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Dabigatran; Warfarin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 19, 2010
• First Posted: June 3, 2010
• Study Start: November 1, 2005
• Primary Completion: September 1, 2006
• Last Updated: March 19, 2014
• Results First Posted: December 17, 2010

Record last verified: 2014-02

Locations

JP (28)