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

NCT00657150 | Completed Phase 3 Results

• 2 other identifiers: 1160.642007-002630-11
• Study Type: interventional
• Target: 2,055
• Locations: 18 countries
• Sites: 104

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period

  Total Venous Thromboembolic Event (VTE) includes both proximal and distal deep vein thrombosis (DVT) (detected by routine venography), symptomatic DVT (confirmed by venous duplex, ultrasound, venography or autopsy) and pulmonary embolism (PE) (confirmed by pulmonary V-Q scintigraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy). All of these components and all deaths were centrally adjudicated by the VTE events committee, which was not aware of the treatment allocation of the patients.

  28-35 days

Secondary Outcomes (11)

• Number of Participants With Major Venous Thromboembolic Event and Venous Thromboembolic Event-related Mortality During Treatment Period

  28-35 days

• Number of Participants With Proximal Deep Vein Thrombosis During Treatment Period

  28-35 days

• Number of Participants With Total Deep Vein Thrombosis During Treatment Period

  28-35 days

• Number of Participants With Symptomatic Deep Vein Thrombosis During Treatment Period

  28-35 days

• Number of Participants With Pulmonary Embolism During Treatment Period

  28-35 days

Study Arms (2)

Dabigatran etexilate

EXPERIMENTAL

220 mg once daily

Drug: Dabigatran etexilate

Enoxaparin

ACTIVE COMPARATOR

40 mg once daily

Drug: Enoxaparin

Interventions

Enoxaparin DRUG

40 mg once daily

Enoxaparin

Dabigatran etexilate DRUG

220 mg once daily

Dabigatran etexilate

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (108)

1160.64.01005 Boehringer Ingelheim Investigational Site

La Jolla, California, United States

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1160.64.01010 Boehringer Ingelheim Investigational Site

Aurora, Colorado, United States

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1160.64.01009 Boehringer Ingelheim Investigational Site

Englewood, Colorado, United States

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1160.64.01012 Boehringer Ingelheim Investigational Site

Clearwater, Florida, United States

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1160.64.01006 Boehringer Ingelheim Investigational Site

Lexington, Kentucky, United States

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1160.64.01003 Boehringer Ingelheim Investigational Site

Missoula, Montana, United States

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1160.64.01007 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

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1160.64.01013 Boehringer Ingelheim Investigational Site

Conway, South Carolina, United States

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1160.64.01002 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

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1160.64.01011 Boehringer Ingelheim Investigational Site

Spokane, Washington, United States

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1160.64.2003 Boehringer Ingelheim Investigational Site

Daws Park, South Australia, Australia

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1160.64.2002 Boehringer Ingelheim Investigational Site

Box Hill, Victoria, Australia

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1160.64.2001 Boehringer Ingelheim Investigational Site

Windsor, Victoria, Australia

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1160.64.2004 Boehringer Ingelheim Investigational Site

Nedlands, Western Australia, Australia

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1160.64.4004 Boehringer Ingelheim Investigational Site

Graz, Austria

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1160.64.4002 Boehringer Ingelheim Investigational Site

Linz, Austria

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1160.64.4001 Boehringer Ingelheim Investigational Site

Vienna, Austria

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1160.64.4003 Boehringer Ingelheim Investigational Site

Wels, Austria

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1160.64.5004 Boehringer Ingelheim Investigational Site

Brussels, Belgium

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1160.64.5002 Boehringer Ingelheim Investigational Site

Deurne, Belgium

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1160.64.5005 Boehringer Ingelheim Investigational Site

Lanaken, Belgium

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1160.64.5001 Boehringer Ingelheim Investigational Site

Leuven, Belgium

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1160.64.6009 Boehringer Ingelheim Investigational Site

Edmonton, Alberta, Canada

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1160.64.6002 Boehringer Ingelheim Investigational Site

Red Deer, Alberta, Canada

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1160.64.6012 Boehringer Ingelheim Investigational Site

Ajax, Ontario, Canada

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1160.64.6003 Boehringer Ingelheim Investigational Site

Belleville, Ontario, Canada

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1160.64.6004 Boehringer Ingelheim Investigational Site

Cambridge, Ontario, Canada

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1160.64.6008 Boehringer Ingelheim Investigational Site

Kitchener, Ontario, Canada

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1160.64.6011 Boehringer Ingelheim Investigational Site

Oshawa, Ontario, Canada

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1160.64.6005 Boehringer Ingelheim Investigational Site

Sarnia, Ontario, Canada

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1160.64.6007 Boehringer Ingelheim Investigational Site

Stratford, Ontario, Canada

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1160.64.6013 Boehringer Ingelheim Investigational Site

Windsor, Ontario, Canada

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1160.64.7004 Boehringer Ingelheim Investigational Site

Chomutov, Czechia

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1160.64.7005 Boehringer Ingelheim Investigational Site

Jihlava, Czechia

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1160.64.7003 Boehringer Ingelheim Investigational Site

Kolín, Czechia

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1160.64.7001 Boehringer Ingelheim Investigational Site

Pilsen, Czechia

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1160.64.7002 Boehringer Ingelheim Investigational Site

Prague, Czechia

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1160.64.8004 Boehringer Ingelheim Investigational Site

Frederiksberg, Denmark

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1160.64.8003 Boehringer Ingelheim Investigational Site

Herlev, Denmark

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1160.64.8001 Boehringer Ingelheim Investigational Site

Hørsholm, Denmark

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1160.64.8002 Boehringer Ingelheim Investigational Site

Silkeborg, Denmark

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1160.64.9002 Boehringer Ingelheim Investigational Site

Jyväskylä, Finland

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1160.64.9001 Boehringer Ingelheim Investigational Site

Oulu, Finland

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1160.64.9003 Boehringer Ingelheim Investigational Site

Tampere, Finland

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1160.64.1104 Boehringer Ingelheim Investigational Site

Garmisch-Partenkirchen, Germany

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1160.64.1101 Boehringer Ingelheim Investigational Site

Mainz, Germany

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1160.64.1103 Boehringer Ingelheim Investigational Site

Markgröningen, Germany

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1160.64.1102 Boehringer Ingelheim Investigational Site

Rheinfelden, Germany

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1160.64.1201 Boehringer Ingelheim Investigational Site

Gyula, Hungary

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1160.64.1203 Boehringer Ingelheim Investigational Site

Kecskemét, Hungary

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1160.64.1202 Boehringer Ingelheim Investigational Site

Szeged, Hungary

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1160.64.1204 Boehringer Ingelheim Investigational Site

Székesfehérvár, Hungary

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1160.64.9105 Boehringer Ingelheim Investigational Site

Ahmedabad, India

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1160.64.9112 Boehringer Ingelheim Investigational Site

Andhra Pradesh, India

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1160.64.9109 Boehringer Ingelheim Investigational Site

Andhra Predesh, India

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1160.64.9103 Boehringer Ingelheim Investigational Site

Bangalore, India

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1160.64.9108 Boehringer Ingelheim Investigational Site

Bangalore, India

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1160.64.9107 Boehringer Ingelheim Investigational Site

Baroda, India

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1160.64.9110 Boehringer Ingelheim Investigational Site

Mangalore, India

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1160.64.9104 Boehringer Ingelheim Investigational Site

Mohali, India

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1160.64.9111 Boehringer Ingelheim Investigational Site

New Delhi, India

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1160.64.9106 Boehringer Ingelheim Investigational Site

Pune, India

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1160.64.9101 Boehringer Ingelheim Investigational Site

Ramdaspeth Nagpur, India

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1160.64.9102 Boehringer Ingelheim Investigational Site

Secunderabad, India

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1160.64.9113 Boehringer Ingelheim Investigational Site

Vadodara, India

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1160.64.1401 Boehringer Ingelheim Investigational Site

Bologna, Italy

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1160.64.1405 Boehringer Ingelheim Investigational Site

Parma, Italy

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1160.64.1402 Boehringer Ingelheim Investigational Site

Pavia, Italy

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1160.64.1407 Boehringer Ingelheim Investigational Site

Reggio Emilia, Italy

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1160.64.1403 Boehringer Ingelheim Investigational Site

Roma, Italy

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1160.64.1404 Boehringer Ingelheim Investigational Site

Torino, Italy

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1160.64.1503 Boehringer Ingelheim Investigational Site

Amsterdam, Netherlands

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1160.64.1507 Boehringer Ingelheim Investigational Site

Amsterdam, Netherlands

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1160.64.1501 Boehringer Ingelheim Investigational Site

Hilversum, Netherlands

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1160.64.1506 Boehringer Ingelheim Investigational Site

Hoofddorp, Netherlands

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1160.64.1510 Boehringer Ingelheim Investigational Site

Leiden, Netherlands

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1160.64.1505 Boehringer Ingelheim Investigational Site

Sittard, Netherlands

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1160.64.1508 Boehringer Ingelheim Investigational Site

Zwolle, Netherlands

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1160.64.3001 Boehringer Ingelheim Investigational Site

Takapuna Auckland, New Zealand

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1160.64.1603 Boehringer Ingelheim Investigational Site

Ålesund, Norway

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1160.64.1601 Boehringer Ingelheim Investigational Site

Bodø, Norway

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1160.64.1606 Boehringer Ingelheim Investigational Site

Elverum, Norway

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1160.64.1604 Boehringer Ingelheim Investigational Site

Lillehammer, Norway

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1160.64.1605 Boehringer Ingelheim Investigational Site

Tynset, Norway

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1160.64.1702 Boehringer Ingelheim Investigational Site

Krakow, Poland

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1160.64.1704 Boehringer Ingelheim Investigational Site

Krakow, Poland

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1160.64.1705 Boehringer Ingelheim Investigational Site

Lodz, Poland

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1160.64.1703 Boehringer Ingelheim Investigational Site

Piekary Śląskie, Poland

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1160.64.1701 Boehringer Ingelheim Investigational Site

Warsaw, Poland

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1160.64.1801 Boehringer Ingelheim Investigational Site

Bryanston, South Africa

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1160.64.1804 Boehringer Ingelheim Investigational Site

Cape Western Province, South Africa

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1160.64.1802 Boehringer Ingelheim Investigational Site

Plumstead, South Africa

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1160.64.1904 Boehringer Ingelheim Investigational Site

Alcorcón (Madrid), Spain

Location

1160.64.1906 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1160.64.1908 Boehringer Ingelheim Investigational Site

Fuenlabrada, Spain

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1160.64.1901 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1160.64.1907 Boehringer Ingelheim Investigational Site

Madrid, Spain

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1160.64.1905 Boehringer Ingelheim Investigational Site

Valencia, Spain

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1160.64.2101 Boehringer Ingelheim Investigational Site

Gothenburg, Sweden

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1160.64.2112 Boehringer Ingelheim Investigational Site

Halmstad, Sweden

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1160.64.2105 Boehringer Ingelheim Investigational Site

Hässleholm, Sweden

Location

1160.64.2109 Boehringer Ingelheim Investigational Site

Kalmar, Sweden

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1160.64.2103 Boehringer Ingelheim Investigational Site

Kungälv, Sweden

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1160.64.2106 Boehringer Ingelheim Investigational Site

Lidköping, Sweden

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1160.64.2102 Boehringer Ingelheim Investigational Site

Motala, Sweden

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1160.64.2108 Boehringer Ingelheim Investigational Site

Stockholm, Sweden

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1160.64.2111 Boehringer Ingelheim Investigational Site

Uppsala, Sweden

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1160.64.2107 Boehringer Ingelheim Investigational Site

Varberg, Sweden

Location

Related Publications (2)

• 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.

  PMID: 26578849 DERIVED

• 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.

  PMID: 21225098 DERIVED

MeSH Terms

Conditions

Venous Thromboembolism

Interventions

Enoxaparin; Dabigatran

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2008
• First Posted: April 14, 2008
• Study Start: March 1, 2008
• Primary Completion: September 1, 2009
• Last Updated: July 2, 2014
• Results First Posted: December 17, 2010

Record last verified: 2013-12

Locations

US (10); AU (4); SE (10); CA (10); BE (4); IN (13); NO (5); ES (6); ZA (3); NZ (1); NL (7); PL (5); IT (6); FI (3); CZ (5); DK (4); DE (4); HU (4)