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

Arthroplasty, Replacement, Knee Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00246025
• Other study ID #: 1160.50
• Status: Completed
• Phase: Phase 2
• First received: October 28, 2005
• Last updated: June 3, 2014
• Start date: October 2005

Study information

• Verified date: February 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 512
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Arthroplasty, Replacement, Knee
• Thromboembolism
• Venous Thromboembolism
• Venous Thrombosis

Intervention

Drug:
• Dabigatran etexilate
Dabigatran etexilate 110 mg capsule, once a day, oral administration
• Dabigatran etexilate
Dabigatran etexilate 150 mg capsule, once a day, oral administration
• Dabigatran Etexilate
Dabigatran etexilate 220 mg capsule, once a day, oral administration
• placebo
matching placebo capsule, once a day, oral administration

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Percentage of Participants With Symptomatic DVT (Deep Vein Thrombosis)	Number of Participants expressing DVT with symptoms	2 weeks	No
Secondary	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	No
Secondary	Number of Participants With Pulmonary Embolism During Treatment Period	Pulmonary embolism confirmed by pulmonary scintigraphy, pulmonary angiography or contrast CT.	2 weeks	No
Secondary	Number of Participants Who Died During Treatment Period	All cause death, as adjudicated by the VTE events committee.	2 weeks	No
Secondary	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	Yes
Secondary	Blood Transfusion	Blood transfusion for treated and operated patients on Day of surgery.	Day 0	No
Secondary	Volume of Blood Loss	Volume of blood loss for treated and operated patients during surgery.	Day 0	No
Secondary	Laboratory Analyses	Frequency of patients with possible clinically significant abnormalities.	First administration to end of study	No

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