A Study of BIBR 1048 in Prevention of Venous Thromboembolism in Patients With TKR Surgery.

A Randomised, Parallel-group, Double-blind, Placebo Controlled Study to Investigate the Efficacy and Safety of BIBR 1048 in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Knee Replacement Surgery

The goal of this study is to evaluate the comparative efficacy and safety of three different doses ( 110 mg, 150 mg, 220 mg) of BIBR 1048 (Dabigatran etexilate) orally, compared to placebo, in prevention of venous thromboembolism in patient with primary elective total knee replacement surgery, and to evaluate dose-response.

Study Overview

• Status: Completed
• Conditions: Venous Thrombosis; Arthroplasty, Replacement, Knee
• Intervention / Treatment: Drug: Dabigatran etexilate; Drug: Dabigatran etexilate; Drug: Dabigatran Etexilate; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 512
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Eniwa, Hokkaido, Japan
    • 1160.50.001 Boehringer Ingelheim Investigational Site
  • Fukuoka, Fukuoka, Japan
    • 1160.50.018 Boehringer Ingelheim Investigational Site
  • Hachioji, Tokyo, Japan
    • 1160.50.008 Boehringer Ingelheim Investigational Site
  • Hirosaki, Aomori, Japan
    • 1160.50.006 Boehringer Ingelheim Investigational Site
  • Hiroshima, Hiroshima, Japan
    • 1160.50.026 Boehringer Ingelheim Investigational Site
  • Iida, Nagano, Japan
    • 1160.50.011 Boehringer Ingelheim Investigational Site
  • Izumisano, Osaka, Japan
    • 1160.50.024 Boehringer Ingelheim Investigational Site
  • Izunokuni,Shizuoka, Japan
    • 1160.50.045 Boehringer Ingelheim Investigational Site
  • Kagoshima, Kagoshima, Japan
    • 1160.50.022 Boehringer Ingelheim Investigational Site
  • Kawasaki, Kanagawa, Japan
    • 1160.50.027 Boehringer Ingelheim Investigational Site
  • Kawasaki, Kanagawa, Japan
    • 1160.50.032 Boehringer Ingelheim Investigational Site
  • Kitakyusyu, Fukuoka, Japan
    • 1160.50.041 Boehringer Ingelheim Investigational Site
  • Koshigaya,Saitama, Japan
    • 1160.50.039 Boehringer Ingelheim Investigational Site
  • Kurume ,Fukuoka, Japan
    • 1160.50.037 Boehringer Ingelheim Investigational Site
  • Kurume ,Fukuoka, Japan
    • 1160.50.038 Boehringer Ingelheim Investigational Site
  • Kyoto, Kyoto, Japan
    • 1160.50.013 Boehringer Ingelheim Investigational Site
  • Matsue, Shimane, Japan
    • 1160.50.036 Boehringer Ingelheim Investigational Site
  • Miyazaki, Miyazaki, Japan
    • 1160.50.042 Boehringer Ingelheim Investigational Site
  • Musashimurayama, Tokyo, Japan
    • 1160.50.028 Boehringer Ingelheim Investigational Site
  • Obihiro, Hokkaido, Japan
    • 1160.50.005 Boehringer Ingelheim Investigational Site
  • Okayama, Okayama, Japan
    • 1160.50.030 Boehringer Ingelheim Investigational Site
  • Omura, Nagasaki, Japan
    • 1160.50.021 Boehringer Ingelheim Investigational Site
  • Osaka, Osaka, Japan
    • 1160.50.014 Boehringer Ingelheim Investigational Site
  • Osaka, Osaka, Japan
    • 1160.50.015 Boehringer Ingelheim Investigational Site
  • Osaka, Osaka, Japan
    • 1160.50.016 Boehringer Ingelheim Investigational Site
  • Osaka, Osaka, Japan
    • 1160.50.033 Boehringer Ingelheim Investigational Site
  • Saga, Saga, Japan
    • 1160.50.031 Boehringer Ingelheim Investigational Site
  • Sagamihara, Kanagawa, Japan
    • 1160.50.009 Boehringer Ingelheim Investigational Site
  • Sapporo, Hokkaido, Japan
    • 1160.50.002 Boehringer Ingelheim Investigational Site
  • Sapporo, Hokkaido, Japan
    • 1160.50.004 Boehringer Ingelheim Investigational Site
  • Sasebo, Nagasaki, Japan
    • 1160.50.020 Boehringer Ingelheim Investigational Site
  • Sasebo, Nagasaki, Japan
    • 1160.50.025 Boehringer Ingelheim Investigational Site
  • Sendai, Miyagi, Japan
    • 1160.50.034 Boehringer Ingelheim Investigational Site
  • Shinjuku-ku,Tokyo, Japan
    • 1160.50.029 Boehringer Ingelheim Investigational Site
  • Shizuoka, Shizuoka, Japan
    • 1160.50.043 Boehringer Ingelheim Investigational Site
  • Sumida-ku, Tokyo, Japan
    • 1160.50.044 Boehringer Ingelheim Investigational Site
  • Tomigusuku, Okinawa, Japan
    • 1160.50.023 Boehringer Ingelheim Investigational Site
  • Tsukuba , Ibaraki, Japan
    • 1160.50.040 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria Inclusion criteria

1. Patients scheduled to undergo a primary, unilateral elective total knee replacement
2. Male or Female 20 years of age or order
3. Patients weighing at least 40 kg
4. Written informed consent prior to the start of study participation

Exclusion criteria Exclusion criteria

1. History of bleeding diathesis
2. Constitutional or acquired coagulation disorders that in the investigator's judgment puts the patient at excessive risk for bleeding
3. Major surgery or trauma (e.g. hip fracture) within the last 3 months
4. Recent unstable cardiovascular disease, such as uncontrolled hypertension at the time of enrollment (investigator's judgment) or history of myocardial infarction within the last 3 months
5. Any history of hemorrhagic stroke or any of the following intracranial pathologies: bleeding, neoplasm, AV (arteriovenous) malformation or aneurysm or recent bleeding history
6. Condition requiring anti-coagulant therapy
7. Elevated AST(Aspartate Aminotransferase) , ALT(Alanine Aminotransferase), or any history of clinically relevant liver disease
8. Patients with a history of clinically significant renal diseases or with elevated creatinine values

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dabigatran etexilate 110 mg; Dabigatran etexilate 110 mg capsule, once a day, oral administration	Drug: Dabigatran etexilate; Dabigatran etexilate 110 mg capsule, once a day, oral administration; Drug: Dabigatran etexilate; Dabigatran etexilate 150 mg capsule, once a day, oral administration
Experimental: Dabigatran etexilate 150 mg; Dabigatran etexilate 150 mg capsule, once a day, oral administration	Drug: Dabigatran etexilate; Dabigatran etexilate 110 mg capsule, once a day, oral administration; Drug: Dabigatran etexilate; Dabigatran etexilate 150 mg capsule, once a day, oral administration
Experimental: Dabigatran etexilate 220 mg; Dabigatran etexilate 110 mg capsule, 2capsules, once a day, oral administration	Drug: Dabigatran Etexilate; Dabigatran etexilate 220 mg capsule, once a day, oral administration
Placebo Comparator: Placebo; matching placebo capsule, once a day, oral administration	Drug: placebo; matching placebo capsule, once a day, oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Have a Composite Endpoint Consisting of Total Venous Thromboembolic Event (VTE) and All Cause Mortality During the Treatment Period.	number of participants with the composite endpoint (total Venous Thromboembolic Event (VTE) and all cause mortality	2 weeks study medication

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Laboratory Analyses	Frequency of patients with possible clinically significant abnormalities.	First administration to end of study
Percentage of Participants Who Have a Composite of Major VTE (Defined as Proximal DVT and PE) and VTE Related Mortality	Number of participants with the composite of major VTE (defined as proximal DVT and PE) and VTE related mortality	2 weeks
Percentage of Participants Who Have Proximal DVT (Deep Vein Thrombosis) During Treatment Period	Number of participants who have Proximal DVT during treatment period	2 weeks
Percentage of Participants With Symptomatic DVT (Deep Vein Thrombosis)	Number of Participants expressing DVT with symptoms	2 weeks
Percentage of Participants Who Have Total DVT (Deep Vein Thrombosis) During Treatment Period	Number of participants who have Total DVT during treatment period	2 weeks
Number of Participants With Pulmonary Embolism During Treatment Period	Pulmonary embolism confirmed by pulmonary scintigraphy, pulmonary angiography or contrast CT.	2 weeks
Number of Participants Who Died During Treatment Period	All cause death, as adjudicated by the VTE events committee.	2 weeks
Number of Participants With Bleeding Events During Treatment Period	Major bleeding events were defined as; fatal; clinically overt associated with loss of haemoglobin >=2g/dL in excess of what was expected; clinically overt leading to the transfusion of >=2 units packed cells or whole blood in excess of what was expected; symptomatic retroperitoneal, intracranial, intraocular or intraspinal; requiring treatment cessation; leading to re-operation Clinically-relevant was defined as; spontaneous skin hematoma >=25 cm²; wound hematoma >=100 cm²; spontaneous nose bleed >5 min; macroscopic hematuria spontaneous or >24 hours if associated with an intervention; spontaneous rectal bleeding (more than a spot on toilet paper); gingival bleeding >5 min; any other bleeding event considered clinically relevant by the investigator Any bleeding events were defined as major, clinically-relevant and minor bleeding events. Minor bleeding events were defined as all other bleeding events that did not fulfil the criteria from above.	2 weeks
Blood Transfusion	Blood transfusion for treated and operated patients on Day of surgery.	Day 0
Volume of Blood Loss	Volume of blood loss for treated and operated patients during surgery.	Day 0

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: October 28, 2005
• First Submitted That Met QC Criteria: October 28, 2005
• First Posted (Estimate): October 30, 2005

Study Record Updates

• Last Update Posted (Estimate): June 9, 2014
• Last Update Submitted That Met QC Criteria: June 3, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran
• Other Study ID Numbers: 1160.50