Dabigatran Etexilate Compared With Enoxaparin in Prevention of Venous Thromboembolism (VTE) Following Total Hip Arthroplasty

NCT ID: NCT00657150

Last Updated: 2014-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 2055 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31

Brief Summary

The primary objective of the trial is to demonstrate non-inferiority of 220 mg oral dabigatran etexilate compared to 40 mg subcutaneous enoxaparin administered once daily. Safety and efficacy will be compared between the treatment groups.

Conditions

Venous Thromboembolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Dabigatran etexilate

220 mg once daily

Group Type: EXPERIMENTAL

Dabigatran etexilate

Intervention Type: DRUG

220 mg once daily

Enoxaparin

40 mg once daily

Group Type: ACTIVE_COMPARATOR

Enoxaparin

Intervention Type: DRUG

40 mg once daily

Interventions

Enoxaparin

40 mg once daily

Intervention Type: DRUG

Dabigatran etexilate

220 mg once daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients scheduled to undergo primary, unilateral, elective total hip arthroplasty.
• Male or female 18 years of age or older.
• Patients giving written informed consent for study participation.

Exclusion Criteria

• Patients weighing less than 40 kg.
• History of bleeding diathesis.
• Patients who in the investigators judgement are perceived as having an excessive risk of bleeding, for example, constitutional or acquired coagulation disorders or because of anticipated need of quinidine, verapamil or other restricted medication during the treatment period (see Section 4.2.2).
• Major surgery or trauma (e.g., hip fracture) within 3 months of enrolment.
• Recent unstable cardiovascular disease (in the investigators opinion) such as uncontrolled hypertension, that is ongoing at the time of enrolment or history of myocardial infarction within 3 months of enrolment.
• Any history of haemorrhagic stroke or any of the following intracranial pathologies: bleeding, neoplasm, Atriovenous (AV) malformation or aneurysm.
• Ongoing treatment for Venous Thromboembolism (VTE).
• Clinically relevant bleeding (gastrointestinal, pulmonary, intraocular or urogenital bleeding) within 6 months of enrolment.
• Gastric or duodenal ulcer within one year of enrolment.
• Liver disease expected to have any potential impact on survival (ie, hepatitis B or C, cirrhosis). This does not include Gilberts syndrome or hepatitis A with complete recovery.
• Active liver disease or liver disease decreasing survival (e.g, acute hepatitis, chronic active hepatitis, cirrhosis) or Alanine Aminotransferase (ALT) >3 x ULN.
• Known severe renal insufficiency (CrCl <30 ml/min). Note: CrCl should be calculated only if serum creatinine is elevated or renal insufficiency is suspected. See Appendix 10.1 for calculation.
• Elevated creatinine that, in the investigators opinion, contraindicates venography.
• Treatment with anticoagulants, clopidogrel, ticlopidine, abciximab, aspirin >162.5 mg/day or NSAID with t 1/2 >12 hours within 7 days prior to hip replacement surgery OR anticipated need while the patient is receiving study medication and prior to 24 hours after the last administration of any blinded study medication (COX-2 selective inhibitors are allowed).
• Anticipated required use of intermittent pneumatic compression and electric stimulation of lower limb.
• Pre-menopausal women (last menstruation within 1 year prior to signing informed consent) who:

• Are pregnant.
• Are nursing.
• Are of child-bearing potential and are NOT practicing acceptable methods of birth control, or do NOT plan to continue practicing an acceptable method throughout the study. Acceptable methods of birth control include intrauterine device; oral, implantable or injectable contraceptives and surgical sterility.
• Known allergy to radio opaque contrast media.
• History of thrombocytopenia, including heparin-induced thrombocytopenia, or a platelet count <100,000 cells/microliter at randomisation.
• Allergy to heparins or dabigatran etexilate.
• Active malignant disease or current cytostatic treatment. Patients should be disease free for at least 5 years.
• Participation in a clinical trial within 30 days of randomisation.
• Leg amputee.
• Known alcohol or drug abuse which would interfere with completion of the study.
• Contraindications to enoxaparin.
• Previous participation in this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

1160.64.01005 Boehringer Ingelheim Investigational Site

La Jolla, California, United States

1160.64.01010 Boehringer Ingelheim Investigational Site

Aurora, Colorado, United States

1160.64.01009 Boehringer Ingelheim Investigational Site

Englewood, Colorado, United States

1160.64.01012 Boehringer Ingelheim Investigational Site

Clearwater, Florida, United States

1160.64.01006 Boehringer Ingelheim Investigational Site

Lexington, Kentucky, United States

1160.64.01003 Boehringer Ingelheim Investigational Site

Missoula, Montana, United States

1160.64.01007 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

1160.64.01013 Boehringer Ingelheim Investigational Site

Conway, South Carolina, United States

1160.64.01002 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

1160.64.01011 Boehringer Ingelheim Investigational Site

Spokane, Washington, United States

1160.64.2003 Boehringer Ingelheim Investigational Site

Daws Park, South Australia, Australia

1160.64.2002 Boehringer Ingelheim Investigational Site

Box Hill, Victoria, Australia

1160.64.2001 Boehringer Ingelheim Investigational Site

Windsor, Victoria, Australia

1160.64.2004 Boehringer Ingelheim Investigational Site

Nedlands, Western Australia, Australia

1160.64.4004 Boehringer Ingelheim Investigational Site

Graz, , Austria

1160.64.4002 Boehringer Ingelheim Investigational Site

Linz, , Austria

1160.64.4001 Boehringer Ingelheim Investigational Site

Vienna, , Austria

1160.64.4003 Boehringer Ingelheim Investigational Site

Wels, , Austria

1160.64.5004 Boehringer Ingelheim Investigational Site

Brussels, , Belgium

1160.64.5002 Boehringer Ingelheim Investigational Site

Deurne, , Belgium

1160.64.5005 Boehringer Ingelheim Investigational Site

Lanaken, , Belgium

1160.64.5001 Boehringer Ingelheim Investigational Site

Leuven, , Belgium

1160.64.6009 Boehringer Ingelheim Investigational Site

Edmonton, Alberta, Canada

1160.64.6002 Boehringer Ingelheim Investigational Site

Red Deer, Alberta, Canada

1160.64.6012 Boehringer Ingelheim Investigational Site

Ajax, Ontario, Canada

1160.64.6003 Boehringer Ingelheim Investigational Site

Belleville, Ontario, Canada

1160.64.6004 Boehringer Ingelheim Investigational Site

Cambridge, Ontario, Canada

1160.64.6008 Boehringer Ingelheim Investigational Site

Kitchener, Ontario, Canada

1160.64.6011 Boehringer Ingelheim Investigational Site

Oshawa, Ontario, Canada

1160.64.6005 Boehringer Ingelheim Investigational Site

Sarnia, Ontario, Canada

1160.64.6007 Boehringer Ingelheim Investigational Site

Stratford, Ontario, Canada

1160.64.6013 Boehringer Ingelheim Investigational Site

Windsor, Ontario, Canada

1160.64.7004 Boehringer Ingelheim Investigational Site

Chomutov, , Czechia

1160.64.7005 Boehringer Ingelheim Investigational Site

Jihlava, , Czechia

1160.64.7003 Boehringer Ingelheim Investigational Site

Kolín, , Czechia

1160.64.7001 Boehringer Ingelheim Investigational Site

Pilsen, , Czechia

1160.64.7002 Boehringer Ingelheim Investigational Site

Prague, , Czechia

1160.64.8004 Boehringer Ingelheim Investigational Site

Frederiksberg, , Denmark

1160.64.8003 Boehringer Ingelheim Investigational Site

Herlev, , Denmark

1160.64.8001 Boehringer Ingelheim Investigational Site

Hørsholm, , Denmark

1160.64.8002 Boehringer Ingelheim Investigational Site

Silkeborg, , Denmark

1160.64.9002 Boehringer Ingelheim Investigational Site

Jyväskylä, , Finland

1160.64.9001 Boehringer Ingelheim Investigational Site

Oulu, , Finland

1160.64.9003 Boehringer Ingelheim Investigational Site

Tampere, , Finland

1160.64.1104 Boehringer Ingelheim Investigational Site

Garmisch-Partenkirchen, , Germany

1160.64.1101 Boehringer Ingelheim Investigational Site

Mainz, , Germany

1160.64.1103 Boehringer Ingelheim Investigational Site

Markgröningen, , Germany

1160.64.1102 Boehringer Ingelheim Investigational Site

Rheinfelden, , Germany

1160.64.1201 Boehringer Ingelheim Investigational Site

Gyula, , Hungary

1160.64.1203 Boehringer Ingelheim Investigational Site

Kecskemét, , Hungary

1160.64.1202 Boehringer Ingelheim Investigational Site

Szeged, , Hungary

1160.64.1204 Boehringer Ingelheim Investigational Site

Székesfehérvár, , Hungary

1160.64.9105 Boehringer Ingelheim Investigational Site

Ahmedabad, , India

1160.64.9112 Boehringer Ingelheim Investigational Site

Andhra Pradesh, , India

1160.64.9109 Boehringer Ingelheim Investigational Site

Andhra Predesh, , India

1160.64.9103 Boehringer Ingelheim Investigational Site

Bangalore, , India

1160.64.9108 Boehringer Ingelheim Investigational Site

Bangalore, , India

1160.64.9107 Boehringer Ingelheim Investigational Site

Baroda, , India

1160.64.9110 Boehringer Ingelheim Investigational Site

Mangalore, , India

1160.64.9104 Boehringer Ingelheim Investigational Site

Mohali, , India

1160.64.9111 Boehringer Ingelheim Investigational Site

New Delhi, , India

1160.64.9106 Boehringer Ingelheim Investigational Site

Pune, , India

1160.64.9101 Boehringer Ingelheim Investigational Site

Ramdaspeth Nagpur, , India

1160.64.9102 Boehringer Ingelheim Investigational Site

Secunderabad, , India

1160.64.9113 Boehringer Ingelheim Investigational Site

Vadodara, , India

1160.64.1401 Boehringer Ingelheim Investigational Site

Bologna, , Italy

1160.64.1405 Boehringer Ingelheim Investigational Site

Parma, , Italy

1160.64.1402 Boehringer Ingelheim Investigational Site

Pavia, , Italy

1160.64.1407 Boehringer Ingelheim Investigational Site

Reggio Emilia, , Italy

1160.64.1403 Boehringer Ingelheim Investigational Site

Roma, , Italy

1160.64.1404 Boehringer Ingelheim Investigational Site

Torino, , Italy

1160.64.1503 Boehringer Ingelheim Investigational Site

Amsterdam, , Netherlands

1160.64.1507 Boehringer Ingelheim Investigational Site

Amsterdam, , Netherlands

1160.64.1501 Boehringer Ingelheim Investigational Site

Hilversum, , Netherlands

1160.64.1506 Boehringer Ingelheim Investigational Site

Hoofddorp, , Netherlands

1160.64.1510 Boehringer Ingelheim Investigational Site

Leiden, , Netherlands

1160.64.1505 Boehringer Ingelheim Investigational Site

Sittard, , Netherlands

1160.64.1508 Boehringer Ingelheim Investigational Site

Zwolle, , Netherlands

1160.64.3001 Boehringer Ingelheim Investigational Site

Takapuna Auckland, , New Zealand

1160.64.1603 Boehringer Ingelheim Investigational Site

Ålesund, , Norway

1160.64.1601 Boehringer Ingelheim Investigational Site

Bodø, , Norway

1160.64.1606 Boehringer Ingelheim Investigational Site

Elverum, , Norway

1160.64.1604 Boehringer Ingelheim Investigational Site

Lillehammer, , Norway

1160.64.1605 Boehringer Ingelheim Investigational Site

Tynset, , Norway

1160.64.1702 Boehringer Ingelheim Investigational Site

Krakow, , Poland

1160.64.1704 Boehringer Ingelheim Investigational Site

Krakow, , Poland

1160.64.1705 Boehringer Ingelheim Investigational Site

Lodz, , Poland

1160.64.1703 Boehringer Ingelheim Investigational Site

Piekary Śląskie, , Poland

1160.64.1701 Boehringer Ingelheim Investigational Site

Warsaw, , Poland

1160.64.1801 Boehringer Ingelheim Investigational Site

Bryanston, , South Africa

1160.64.1804 Boehringer Ingelheim Investigational Site

Cape Western Province, , South Africa

1160.64.1802 Boehringer Ingelheim Investigational Site

Plumstead, , South Africa

1160.64.1904 Boehringer Ingelheim Investigational Site

Alcorcón (Madrid), , Spain

1160.64.1906 Boehringer Ingelheim Investigational Site

Barcelona, , Spain

1160.64.1908 Boehringer Ingelheim Investigational Site

Fuenlabrada, , Spain

1160.64.1901 Boehringer Ingelheim Investigational Site

Madrid, , Spain

1160.64.1907 Boehringer Ingelheim Investigational Site

Madrid, , Spain

1160.64.1905 Boehringer Ingelheim Investigational Site

Valencia, , Spain

1160.64.2101 Boehringer Ingelheim Investigational Site

Gothenburg, , Sweden

1160.64.2112 Boehringer Ingelheim Investigational Site

Halmstad, , Sweden

1160.64.2105 Boehringer Ingelheim Investigational Site

Hässleholm, , Sweden

1160.64.2109 Boehringer Ingelheim Investigational Site

Kalmar, , Sweden

1160.64.2103 Boehringer Ingelheim Investigational Site

Kungälv, , Sweden

1160.64.2106 Boehringer Ingelheim Investigational Site

Lidköping, , Sweden

1160.64.2102 Boehringer Ingelheim Investigational Site

Motala, , Sweden

1160.64.2108 Boehringer Ingelheim Investigational Site

Stockholm, , Sweden

1160.64.2111 Boehringer Ingelheim Investigational Site

Uppsala, , Sweden

1160.64.2107 Boehringer Ingelheim Investigational Site

Varberg, , Sweden

Countries

United States; Australia; Austria; Belgium; Canada; Czechia; Denmark; Finland; Germany; Hungary; India; Italy; Netherlands; New Zealand; Norway; Poland; South Africa; Spain; Sweden

References

Eriksson BI, Dahl OE, Rosencher N, Clemens A, Hantel S, Feuring M, Kreuzer J, Huo M, Friedman RJ. Oral dabigatran etexilate versus enoxaparin for venous thromboembolism prevention after total hip arthroplasty: pooled analysis of two phase 3 randomized trials. Thromb J. 2015 Nov 17;13:36. doi: 10.1186/s12959-015-0067-8. eCollection 2015.

Reference Type: DERIVED

PMID: 26578849 (View on PubMed)

Eriksson BI, Dahl OE, Huo MH, Kurth AA, Hantel S, Hermansson K, Schnee JM, Friedman RJ; RE-NOVATE II Study Group. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, double-blind, non-inferiority trial. Thromb Haemost. 2011 Apr;105(4):721-9. doi: 10.1160/TH10-10-0679. Epub 2011 Jan 12.

Reference Type: DERIVED

PMID: 21225098 (View on PubMed)

Other Identifiers

2007-002630-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1160.64

Identifier Type: -

Identifier Source: org_study_id