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

June 23, 2014 updated by: Boehringer Ingelheim

A Phase III Randomised, Parallel Group, Double-blind, Active Controlled Study to Investigate the Efficacy and Safety of Orally Administered 220 mg Dabigatran Etexilate Capsules (110 mg Administered on the Day of Surgery Followed by 220 mg Once Daily) Compared to Subcutaneous 40 mg Enoxaparin Once Daily for 28-35 Days, in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Hip Arthroplasty Surgery. (RE-NOVATE II)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

2055

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • South Australia
      • Daws Park, South Australia, Australia
        • 1160.64.2003 Boehringer Ingelheim Investigational Site
    • Victoria
      • Box HIll, Victoria, Australia
        • 1160.64.2002 Boehringer Ingelheim Investigational Site
      • Windsor, Victoria, Australia
        • 1160.64.2001 Boehringer Ingelheim Investigational Site
    • Western Australia
      • Nedlands, Western Australia, Australia
        • 1160.64.2004 Boehringer Ingelheim Investigational Site
  • Austria
      • Graz, Austria
        • 1160.64.4004 Boehringer Ingelheim Investigational Site
      • Linz, Austria
        • 1160.64.4002 Boehringer Ingelheim Investigational Site
      • Wels, Austria
        • 1160.64.4003 Boehringer Ingelheim Investigational Site
      • Wien, Austria
        • 1160.64.4001 Boehringer Ingelheim Investigational Site
  • Belgium
      • Brussel, Belgium
        • 1160.64.5004 Boehringer Ingelheim Investigational Site
      • Deurne, Belgium
        • 1160.64.5002 Boehringer Ingelheim Investigational Site
      • Lanaken, Belgium
        • 1160.64.5005 Boehringer Ingelheim Investigational Site
      • Leuven, Belgium
        • 1160.64.5001 Boehringer Ingelheim Investigational Site
  • Canada
    • Alberta
      • Edmonton,, Alberta, Canada
        • 1160.64.6009 Boehringer Ingelheim Investigational Site
      • Red Deer, Alberta, Canada
        • 1160.64.6002 Boehringer Ingelheim Investigational Site
    • Ontario
      • Ajax, Ontario, Canada
        • 1160.64.6012 Boehringer Ingelheim Investigational Site
      • Belleville, Ontario, Canada
        • 1160.64.6003 Boehringer Ingelheim Investigational Site
      • Cambridge, Ontario, Canada
        • 1160.64.6004 Boehringer Ingelheim Investigational Site
      • Kitchener, Ontario, Canada
        • 1160.64.6008 Boehringer Ingelheim Investigational Site
      • Oshawa, Ontario, Canada
        • 1160.64.6011 Boehringer Ingelheim Investigational Site
      • Sarnia, Ontario, Canada
        • 1160.64.6005 Boehringer Ingelheim Investigational Site
      • Stratford, Ontario, Canada
        • 1160.64.6007 Boehringer Ingelheim Investigational Site
      • Windsor, Ontario, Canada
        • 1160.64.6013 Boehringer Ingelheim Investigational Site
  • Czech Republic
      • Chomutov, Czech Republic
        • 1160.64.7004 Boehringer Ingelheim Investigational Site
      • Jihlava, Czech Republic
        • 1160.64.7005 Boehringer Ingelheim Investigational Site
      • Kolin, Czech Republic
        • 1160.64.7003 Boehringer Ingelheim Investigational Site
      • Plzen, Czech Republic
        • 1160.64.7001 Boehringer Ingelheim Investigational Site
      • Prague 8, Czech Republic
        • 1160.64.7002 Boehringer Ingelheim Investigational Site
  • Denmark
      • Frederiksberg, Denmark
        • 1160.64.8004 Boehringer Ingelheim Investigational Site
      • Herlev, Denmark
        • 1160.64.8003 Boehringer Ingelheim Investigational Site
      • Hørsholm, Denmark
        • 1160.64.8001 Boehringer Ingelheim Investigational Site
      • Silkeborg, Denmark
        • 1160.64.8002 Boehringer Ingelheim Investigational Site
  • Finland
      • Jyväskylä, Finland
        • 1160.64.9002 Boehringer Ingelheim Investigational Site
      • Oulu, Finland
        • 1160.64.9001 Boehringer Ingelheim Investigational Site
      • Tampere, Finland
        • 1160.64.9003 Boehringer Ingelheim Investigational Site
  • Germany
      • Garmisch-Partenkirchen, Germany
        • 1160.64.1104 Boehringer Ingelheim Investigational Site
      • Mainz, Germany
        • 1160.64.1101 Boehringer Ingelheim Investigational Site
      • Markgröningen, Germany
        • 1160.64.1103 Boehringer Ingelheim Investigational Site
      • Rheinfelden, Germany
        • 1160.64.1102 Boehringer Ingelheim Investigational Site
  • Hungary
      • Gyula, Hungary
        • 1160.64.1201 Boehringer Ingelheim Investigational Site
      • Kecskemét, Hungary
        • 1160.64.1203 Boehringer Ingelheim Investigational Site
      • Szeged, Hungary
        • 1160.64.1202 Boehringer Ingelheim Investigational Site
      • Székesfehérvár, Hungary
        • 1160.64.1204 Boehringer Ingelheim Investigational Site
  • India
      • Ahmedabad, India
        • 1160.64.9105 Boehringer Ingelheim Investigational Site
      • Andhra Pradesh, India
        • 1160.64.9112 Boehringer Ingelheim Investigational Site
      • Andhra Predesh, India
        • 1160.64.9109 Boehringer Ingelheim Investigational Site
      • Bangalore, India
        • 1160.64.9103 Boehringer Ingelheim Investigational Site
      • Bangalore, India
        • 1160.64.9108 Boehringer Ingelheim Investigational Site
      • Baroda, India
        • 1160.64.9107 Boehringer Ingelheim Investigational Site
      • Mangalore, India
        • 1160.64.9110 Boehringer Ingelheim Investigational Site
      • Mohali, India
        • 1160.64.9104 Boehringer Ingelheim Investigational Site
      • New Delhi, India
        • 1160.64.9111 Boehringer Ingelheim Investigational Site
      • Pune, India
        • 1160.64.9106 Boehringer Ingelheim Investigational Site
      • Ramdaspeth Nagpur, India
        • 1160.64.9101 Boehringer Ingelheim Investigational Site
      • Secunderabad, India
        • 1160.64.9102 Boehringer Ingelheim Investigational Site
      • Vadodara, India
        • 1160.64.9113 Boehringer Ingelheim Investigational Site
  • Italy
      • Bologna, Italy
        • 1160.64.1401 Boehringer Ingelheim Investigational Site
      • Parma, Italy
        • 1160.64.1405 Boehringer Ingelheim Investigational Site
      • Pavia, Italy
        • 1160.64.1402 Boehringer Ingelheim Investigational Site
      • Reggio Emilia, Italy
        • 1160.64.1407 Boehringer Ingelheim Investigational Site
      • Roma, Italy
        • 1160.64.1403 Boehringer Ingelheim Investigational Site
      • Torino, Italy
        • 1160.64.1404 Boehringer Ingelheim Investigational Site
  • Netherlands
      • Amsterdam, Netherlands
        • 1160.64.1503 Boehringer Ingelheim Investigational Site
      • Amsterdam, Netherlands
        • 1160.64.1507 Boehringer Ingelheim Investigational Site
      • Hilversum, Netherlands
        • 1160.64.1501 Boehringer Ingelheim Investigational Site
      • Hoofddorp, Netherlands
        • 1160.64.1506 Boehringer Ingelheim Investigational Site
      • Leiden, Netherlands
        • 1160.64.1510 Boehringer Ingelheim Investigational Site
      • Sittard, Netherlands
        • 1160.64.1505 Boehringer Ingelheim Investigational Site
      • Zwolle, Netherlands
        • 1160.64.1508 Boehringer Ingelheim Investigational Site
  • New Zealand
      • Takapuna Auckland, New Zealand
        • 1160.64.3001 Boehringer Ingelheim Investigational Site
  • Norway
      • Bodø, Norway
        • 1160.64.1601 Boehringer Ingelheim Investigational Site
      • Elverum, Norway
        • 1160.64.1606 Boehringer Ingelheim Investigational Site
      • Lillehammer, Norway
        • 1160.64.1604 Boehringer Ingelheim Investigational Site
      • Tynset, Norway
        • 1160.64.1605 Boehringer Ingelheim Investigational Site
      • Ålesund, Norway
        • 1160.64.1603 Boehringer Ingelheim Investigational Site
  • Poland
      • Krakow, Poland
        • 1160.64.1702 Boehringer Ingelheim Investigational Site
      • Krakow, Poland
        • 1160.64.1704 Boehringer Ingelheim Investigational Site
      • Lodz, Poland
        • 1160.64.1705 Boehringer Ingelheim Investigational Site
      • Piekary Slaskie, Poland
        • 1160.64.1703 Boehringer Ingelheim Investigational Site
      • Warsaw, Poland
        • 1160.64.1701 Boehringer Ingelheim Investigational Site
  • South Africa
      • Bryanston, South Africa
        • 1160.64.1801 Boehringer Ingelheim Investigational Site
      • Cape Western Province, South Africa
        • 1160.64.1804 Boehringer Ingelheim Investigational Site
      • Plumstead, South Africa
        • 1160.64.1802 Boehringer Ingelheim Investigational Site
  • Spain
      • Alcorcón (Madrid), Spain
        • 1160.64.1904 Boehringer Ingelheim Investigational Site
      • Barcelona, Spain
        • 1160.64.1906 Boehringer Ingelheim Investigational Site
      • Fuenlabrada, Spain
        • 1160.64.1908 Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • 1160.64.1901 Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • 1160.64.1907 Boehringer Ingelheim Investigational Site
      • Valencia, Spain
        • 1160.64.1905 Boehringer Ingelheim Investigational Site
  • Sweden
      • Göteborg, Sweden
        • 1160.64.2101 Boehringer Ingelheim Investigational Site
      • Halmstad, Sweden
        • 1160.64.2112 Boehringer Ingelheim Investigational Site
      • Hässleholm, Sweden
        • 1160.64.2105 Boehringer Ingelheim Investigational Site
      • Kalmar, Sweden
        • 1160.64.2109 Boehringer Ingelheim Investigational Site
      • Kungälv, Sweden
        • 1160.64.2103 Boehringer Ingelheim Investigational Site
      • Lidköping, Sweden
        • 1160.64.2106 Boehringer Ingelheim Investigational Site
      • Motala, Sweden
        • 1160.64.2102 Boehringer Ingelheim Investigational Site
      • Stockholm, Sweden
        • 1160.64.2108 Boehringer Ingelheim Investigational Site
      • Uppsala, Sweden
        • 1160.64.2111 Boehringer Ingelheim Investigational Site
      • Varberg, Sweden
        • 1160.64.2107 Boehringer Ingelheim Investigational Site
  • United States
    • California
      • La Jolla, California, United States
        • 1160.64.01005 Boehringer Ingelheim Investigational Site
    • Colorado
      • Aurora, Colorado, United States
        • 1160.64.01010 Boehringer Ingelheim Investigational Site
      • Englewood, Colorado, United States
        • 1160.64.01009 Boehringer Ingelheim Investigational Site
    • Florida
      • Clearwater, Florida, United States
        • 1160.64.01012 Boehringer Ingelheim Investigational Site
    • Kentucky
      • Lexington, Kentucky, United States
        • 1160.64.01006 Boehringer Ingelheim Investigational Site
    • Montana
      • Missoula, Montana, United States
        • 1160.64.01003 Boehringer Ingelheim Investigational Site
    • South Carolina
      • Charleston, South Carolina, United States
        • 1160.64.01007 Boehringer Ingelheim Investigational Site
      • Conway, South Carolina, United States
        • 1160.64.01013 Boehringer Ingelheim Investigational Site
    • Texas
      • Houston, Texas, United States
        • 1160.64.01002 Boehringer Ingelheim Investigational Site
    • Washington
      • Spokane, Washington, United States
        • 1160.64.01011 Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dabigatran etexilate
220 mg once daily
Drug: Dabigatran etexilate
220 mg once daily
Active Comparator: Enoxaparin
40 mg once daily
Drug: Enoxaparin
40 mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period
Time Frame: 28-35 days

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Volume of Blood Loss
Time Frame: Day 1
Volume of blood loss for treated and operated patients during surgery.
Day 1
Laboratory Analyses
Time Frame: First administration to end of study
Frequency of patients with possible clinically significant abnormalities.
First administration to end of study
Number of Participants With Major Venous Thromboembolic Event and Venous Thromboembolic Event-related Mortality During Treatment Period
Time Frame: 28-35 days
Major Venous Thromboembolic Event (VTE) is defined as proximal DVT and PE, as adjudicated by the VTE events committee
28-35 days
Number of Participants With Proximal Deep Vein Thrombosis During Treatment Period
Time Frame: 28-35 days
Proximal Deep Vein Thrombosis as adjudicated by the VTE events committee
28-35 days
Number of Participants With Total Deep Vein Thrombosis During Treatment Period
Time Frame: 28-35 days
Total Deep Vein Thrombosis as adjudicated by the VTE events committee
28-35 days
Number of Participants With Symptomatic Deep Vein Thrombosis During Treatment Period
Time Frame: 28-35 days
Symptomatic Deep Vein Thrombosis, confirmed by venous duplex, ultrasound, venography or autopsy, and as adjudicated by the VTE events committee
28-35 days
Number of Participants With Pulmonary Embolism During Treatment Period
Time Frame: 28-35 days
Pulmonary embolism confirmed by pulmonary V-Q scintigraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy, and as adjudicated by the VTE events committee
28-35 days
Number of Participants Who Died During Treatment Period
Time Frame: 28-35 days
All cause death, as adjudicated by the VTE events committee
28-35 days
Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period
Time Frame: 3 months
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).
3 months
Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period
Time Frame: 28-35 days

Major bleeding events were defined as

  • fatal
  • clinically overt associated with loss of haemoglobin >=20g/L 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
  • 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.
28-35 days
Blood Transfusion
Time Frame: Day 1
Number of treated and operated patients with required blood transfusion on day of surgery.
Day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2008

Primary Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

March 27, 2008

First Submitted That Met QC Criteria

April 11, 2008

First Posted (Estimate)

April 14, 2008

Study Record Updates

Last Update Posted (Estimate)

July 2, 2014

Last Update Submitted That Met QC Criteria

June 23, 2014

Last Verified

December 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1160.64
  • 2007-002630-11 (EudraCT Number: EudraCT)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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