Dabigatran Etexilate in Extended Venous Thromboembolism (VTE) Prevention After Hip Replacement Surgery

May 8, 2014 updated by: Boehringer Ingelheim

A Phase III Randomised, Parallel Group, Double-blind, Active Controlled Study to Investigate the Efficacy and Safety of Two Different Dose Regimens of Orally Administered Dabigatran Etexilate Capsules [150 or 220 mg Once Daily Starting With Half Dose (75 or 110 mg) on the Day of Surgery] Compared to Subcutaneous Enoxaparin 40 mg Once Daily for 28-35 Days, in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Hip Replacement Surgery. RE-NOVATE (Extended Thromboembolism Prevention After Hip Surgery)

The objective of this study is to determine the comparative efficacy and safety of two oral regimens of dabigatran etexilate, compared to a standard subcutaneous regimen of enoxaparin, in prevention of venous thromboembolism in patients with primary elective total hip replacement surgery.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

3494

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
    • Australian Capital Territory
      • Garren, Australian Capital Territory, Australia
        • 1160.48.06108 Canberra Hospital
    • New South Wales
      • Kogarah, New South Wales, Australia
        • 1160.48.06106 St George Public Hospital
      • Lismore, New South Wales, Australia
        • 1160.48.06110 Suite 13 level 4
    • South Australia
      • Bedford Park, South Australia, Australia
        • 1160.48.06105 Flinders Medical Centre
    • Victoria
      • Box Hill, Victoria, Australia
        • 1160.48.06104 Ecru
      • Clayton, Victoria, Australia
        • 1160.48.06102 Monash Medical Centre
      • Malvern, Victoria, Australia
        • 1160.48.06101 Emeritus Research
      • Ringwood East, Victoria, Australia
        • 1160.48.06103 Maroondah Hospital
      • Windsor, Victoria, Australia
        • 1160.48.06113
    • Western Australia
      • Perth, Western Australia, Australia
        • 1160.48.06111 Haemophillia & Thrombosis Service
  • Austria
      • Linz, Austria
        • 1160.48.04304 Boehringer Ingelheim Investigational Site
      • Wels, Austria
        • 1160.48.04303 Boehringer Ingelheim Investigational Site
      • Wien, Austria
        • 1160.48.04302 Boehringer Ingelheim Investigational Site
      • Wr. Neustadt, Austria
        • 1160.48.04301 Boehringer Ingelheim Investigational Site
  • Belgium
      • Brussels, Belgium
        • 1160.48.03207 UVC Brugmann
      • Gent, Belgium
        • 1160.48.03206 Campus Sint-Lucas
      • Gent, Belgium
        • 1160.48.03208 UZ Gent
      • Hasselt, Belgium
        • 1160.48.03202 Boehringer Ingelheim Investigational Site
      • Herentals, Belgium
        • 1160.48.03203 AZ Sint Elisabeth
      • Lanaken, Belgium
        • 1160.48.03205 Ziekenhuis Oost-Limburg
      • Leuven, Belgium
        • 1160.48.03201 UZ Gasthuisberg
  • Czech Republic
      • Brno-Bohunice, Czech Republic
        • 1160.48.42004 Boehringer Ingelheim Investigational Site
      • Chomutov, Czech Republic
        • 1160.48.42010 Boehringer Ingelheim Investigational Site
      • Havlickuv Brod, Czech Republic
        • 1160.48.42009 Boehringer Ingelheim Investigational Site
      • Jihlava, Czech Republic
        • 1160.48.42008 Boehringer Ingelheim Investigational Site
      • Kladno, Czech Republic
        • 1160.48.42002 Boehringer Ingelheim Investigational Site
      • Kolin, Czech Republic
        • 1160.48.42006 Boehringer Ingelheim Investigational Site
      • Ostrava, Czech Republic
        • 1160.48.42003 Boehringer Ingelheim Investigational Site
      • Plzen, Czech Republic
        • 1160.48.42001 Boehringer Ingelheim Investigational Site
      • Pradubice, Czech Republic
        • 1160.48.42007 Boehringer Ingelheim Investigational Site
      • Prague 8, Czech Republic
        • 1160.48.42005 Boehringer Ingelheim Investigational Site
  • Denmark
      • Hellerup, Denmark
        • 1160.48.04571 Boehringer Ingelheim Investigational Site
      • Hørsholm, Denmark
        • 1160.48.04570 Boehringer Ingelheim Investigational Site
      • København NV, Denmark
        • 1160.48.04573 Boehringer Ingelheim Investigational Site
      • København S, Denmark
        • 1160.48.04574 Boehringer Ingelheim Investigational Site
      • Silkeborg, Denmark
        • 1160.48.04575 Boehringer Ingelheim Investigational Site
  • Finland
      • Helsinki, Finland
        • 1160.48.35803 Boehringer Ingelheim Investigational Site
      • Jyväskylä, Finland
        • 1160.48.35802 Boehringer Ingelheim Investigational Site
      • Oulu, Finland
        • 1160.48.35801 Boehringer Ingelheim Investigational Site
      • Seinäjoki, Finland
        • 1160.48.35804 Boehringer Ingelheim Investigational Site
      • Tampere, Finland
        • 1160.48.35805 Boehringer Ingelheim Investigational Site
  • France
      • Amiens cedex 1, France
        • 1160.48.03304 Boehringer Ingelheim Investigational Site
      • Roubaix cedex, France
        • 1160.48.03303 Boehringer Ingelheim Investigational Site
      • Soyaux, France
        • 1160.48.03302 Boehringer Ingelheim Investigational Site
      • Strasbourg, France
        • 1160.48.03308 Boehringer Ingelheim Investigational Site
  • Germany
      • Bad Mergentheim, Germany
        • 1160.48.04906 Caritaskrankenhaus
      • Erlangen, Germany
        • 1160.48.04910 F.-A.-Universität Erlangen-Nürnberg
      • Frankfurt, Germany
        • 1160.48.04904 Orthopädische Universitätsklinik
      • Garmisch-Partenkirchen, Germany
        • 1160.48.04902 Klinikum Garmisch-Partenkirchen
      • Kamp-Lintfort, Germany
        • 1160.48.04914 St. Bernhard-Hospital
      • Mainz, Germany
        • 1160.48.04907 Johannes Gutenberg-Universität Mainz
      • Markgröningen, Germany
        • 1160.48.04912 Orthopädische Klinik Markgröningen gGmbH
      • Rheinfelden, Germany
        • 1160.48.04901 Kreiskrankenhaus
      • Schwandorf, Germany
        • 1160.48.04915 Orthopädische Klinik Lindenlohe
      • Sommerfeld, Germany
        • 1160.48.04903 Hellmuth-Ulrici-Kliniken
      • Wiesbaden, Germany
        • 1160.48.04905 Aukammklinik
  • Hungary
      • Budapest, Hungary
        • 1160.48.03603 Boehringer Ingelheim Investigational Site
      • Budapest, Hungary
        • 1160.48.03606 Boehringer Ingelheim Investigational Site
      • Békéscsaba, Hungary
        • 1160.48.03607 Boehringer Ingelheim Investigational Site
      • Gyula, Hungary
        • 1160.48.03601 Boehringer Ingelheim Investigational Site
      • Kecskemét, Hungary
        • 1160.48.03604 Boehringer Ingelheim Investigational Site
      • Szeged, Hungary
        • 1160.48.03602 Boehringer Ingelheim Investigational Site
      • Székesfehérvár, Hungary
        • 1160.48.03605 Boehringer Ingelheim Investigational Site
  • Italy
      • Bergamo, Italy
        • 1160.48.03903 Boehringer Ingelheim Investigational Site
      • Bologna, Italy
        • 1160.48.03904 Boehringer Ingelheim Investigational Site
      • Milano, Italy
        • 1160.48.03902 Boehringer Ingelheim Investigational Site
      • Pavia, Italy
        • 1160.48.03901 Boehringer Ingelheim Investigational Site
  • Netherlands
      • Amsterdam, Netherlands
        • 1160.48.03102 Boehringer Ingelheim Investigational Site
      • Heemstede, Netherlands
        • 1160.48.03101 Boehringer Ingelheim Investigational Site
      • Helmond, Netherlands
        • 1160.48.03107 Boehringer Ingelheim Investigational Site
      • Hilversum, Netherlands
        • 1160.48.03103 Boehringer Ingelheim Investigational Site
      • Nijmegen, Netherlands
        • 1160.48.03104 Boehringer Ingelheim Investigational Site
      • Sittard, Netherlands
        • 1160.48.03105 Boehringer Ingelheim Investigational Site
  • Norway
      • Bodø, Norway
        • 1160.48.04701 Boehringer Ingelheim Investigational Site
      • Bærum Postterminal, Norway
        • 1160.48.04704 Boehringer Ingelheim Investigational Site
      • Bærum Postterminal, Norway
        • 1160.48.04707 Boehringer Ingelheim Investigational Site
      • Elverum, Norway
        • 1160.48.04706 Boehringer Ingelheim Investigational Site
      • Skien, Norway
        • 1160.48.04702 Boehringer Ingelheim Investigational Site
      • Ålesund, Norway
        • 1160.48.04703 Boehringer Ingelheim Investigational Site
  • Poland
      • Bialystok, Poland
        • 1160.48.04810 Boehringer Ingelheim Investigational Site
      • Kielce, Poland
        • 1160.48.04804 Boehringer Ingelheim Investigational Site
      • Krakow, Poland
        • 1160.48.04806 Boehringer Ingelheim Investigational Site
      • Krakow, Poland
        • 1160.48.04807 Boehringer Ingelheim Investigational Site
      • Krakow, Poland
        • 1160.48.04812 Boehringer Ingelheim Investigational Site
      • Lodz, Poland
        • 1160.48.04820 Boehringer Ingelheim Investigational Site
      • Mielec, Poland
        • 1160.48.04814 Boehringer Ingelheim Investigational Site
      • Piekary Slaskie, Poland
        • 1160.48.04808 Boehringer Ingelheim Investigational Site
      • Rzeszow, Poland
        • 1160.48.04817 Boehringer Ingelheim Investigational Site
      • Warsaw, Poland
        • 1160.48.04801 Boehringer Ingelheim Investigational Site
      • Warsaw, Poland
        • 1160.48.04802 Boehringer Ingelheim Investigational Site
      • Warsaw, Poland
        • 1160.48.04803 Boehringer Ingelheim Investigational Site
  • South Africa
      • Bryanston, South Africa
        • 1160.48.02701 Boehringer Ingelheim Investigational Site
      • Johannesburg, South Africa
        • 1160.48.02704 Boehringer Ingelheim Investigational Site
      • Randburg, South Africa
        • 1160.48.02703 Boehringer Ingelheim Investigational Site
      • Sandton, South Africa
        • 1160.48.02702 Boehringer Ingelheim Investigational Site
  • Spain
      • Alcorcón (Madrid), Spain
        • 1160.48.03405 Boehringer Ingelheim Investigational Site
      • Barcelona, Spain
        • 1160.48.03403 Boehringer Ingelheim Investigational Site
      • Barcelona, Spain
        • 1160.48.03411 Boehringer Ingelheim Investigational Site
      • Hospitalet (Barcelona), Spain
        • 1160.48.03407 Boehringer Ingelheim Investigational Site
      • Jaén, Spain
        • 1160.48.03409 Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • 1160.48.03401 Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • 1160.48.03402 Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • 1160.48.03404 Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • 1160.48.03406 Boehringer Ingelheim Investigational Site
      • Móstoles (Madrid), Spain
        • 1160.48.03408 Boehringer Ingelheim Investigational Site
      • Valencia, Spain
        • 1160.48.03410 Boehringer Ingelheim Investigational Site
  • Sweden
      • Falköping, Sweden
        • 1160.48.04602 Boehringer Ingelheim Investigational Site
      • Göteborg, Sweden
        • 1160.48.04601 Boehringer Ingelheim Investigational Site
      • Halmstad, Sweden
        • 1160.48.04607 Boehringer Ingelheim Investigational Site
      • Kalmar, Sweden
        • 1160.48.04606 Boehringer Ingelheim Investigational Site
      • Kungälv, Sweden
        • 1160.48.04603 Boehringer Ingelheim Investigational Site
      • Lidköping, Sweden
        • 1160.48.04608 Boehringer Ingelheim Investigational Site
      • Linköping, Sweden
        • 1160.48.04605 Boehringer Ingelheim Investigational Site
      • Mölndal, Sweden
        • 1160.48.04604 Boehringer Ingelheim Investigational Site
      • Stockholm, Sweden
        • 1160.48.04610 Boehringer Ingelheim Investigational Site
      • Varberg, Sweden
        • 1160.48.04609 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

Inclusion criteria (selected):

  • Patients (18 years or older) scheduled to undergo a primary, unilateral, elective total hip replacement
  • Written Informed Consent

Exclusion criteria

Exclusion criteria (selected):

  • Patients with an excessive risk of bleeding, for example because of history of bleeding diathesis major surgery or trauma within the last 3 months history of haemorrhagic stroke or any of the following intracranial pathologies: bleeding, neoplasm, AV malformation or aneurysm clinically relevant bleeding or gastric / duodenal ulcer within the last 6 months treatment with anticoagulants within 7 days prior to joint replacement surgery or anticipated need during the study treatment period thrombocytopenia.
  • Active malignant disease or current cytostatic treatment
  • Known severe renal insufficiency
  • Liver disease expected to have any potential impact on survival, or elevated AST or ALT > 2x upper limit of normal
  • Recent unstable cardiovascular disease or history of myocardial infarction within the last 3 months
  • Pre-menopausal women who are pregnant or nursing, or are of child-bearing potential and are not practising or do not plan to continue practising acceptable methods of birth control
  • Allergy to radio opaque contrast media or iodine, heparins (incl. heparin induced thrombocytopenia) or dabigatran
  • Contraindications to enoxaparin
  • Participation in a clinical trial during the last 30 days

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
Active Comparator: enoxaparin
40 mg once daily
Drug: enoxaparin
40 mg once daily
Experimental: dabigatran etexilate 75 mg
daily dose 150 mg once daily, half a dose on the day of surgery
Drug: dabigatran etexilate
daily dose 150 mg once daily, half a dose on the day of surgery
Experimental: dabigatran etexilate 110 mg
daily dose 220 mg once daily, half a dose on the day of surgery
Drug: dabigatran etexilate
daily dose 150 mg once daily, half a dose on the day of surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period
Time Frame: First administration until 31-38 days

Total Venous Thromboembolic Event (VTE) includes both proximal and distal deep vein thrombosis (DVT) (detected by routine bilateral venography), symptomatic DVT (confirmed by venous compression 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.
First administration until 31-38 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood Transfusion
Time Frame: Day 1
Blood transfusion for treated and operated patients on Day of surgery.
Day 1
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
Major Venous Thromboembolic Event and Venous Thromboembolic Event-related Mortality During Treatment Period
Time Frame: First administration until 31-38 days
Major Venous Thromboembolic Event (VTE) is defined as proximal DVT and PE, as adjudicated by the VTE events committee
First administration until 31-38 days
Proximal Deep Vein Thrombosis During Treatment Period
Time Frame: First administration until 31-38 days
Proximal Deep Vein Thrombosis as adjudicated by the VTE events committee
First administration until 31-38 days
Total Deep Vein Thrombosis During Treatment Period
Time Frame: First administration until 31-38 days
Total Deep Vein Thrombosis as adjudicated by the VTE events committee
First administration until 31-38 days
Symptomatic Deep Vein Thrombosis During Treatment Period
Time Frame: First administration until 31-38 days
Symptomatic Deep Vein Thrombosis, confirmed by venous compression ultrasound, venography or autopsy, and as adjudicated by the VTE events committee
First administration until 31-38 days
Pulmonary Embolism During Treatment Period
Time Frame: First administration until 31-38 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
First administration until 31-38 days
Death During Treatment Period
Time Frame: First administration until 31-38 days
All cause death, as adjudicated by the VTE events committee
First administration until 31-38 days
Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period
Time Frame: end of treatment to day 91±7
Total Venous Thromboembolic Event (VTE) includes both proximal and distal deep vein thrombosis (DVT) (detected by routine bilateral venography), symptomatic DVT (confirmed by venous compression ultrasound, venography or autopsy) and pulmonary embolism (PE) (confirmed by pulmonary V-Q scintigraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy).
end of treatment to day 91±7
Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period
Time Frame: First administration until 31-38 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 greater than or equal to 25 cm²
  • wound hematoma greater than or equal to 100 cm²
  • spontaneous nose bleed lasting longer than 5 min
  • macroscopic hematuria spontaneous or lasting longer than 24 hours if associated with an intervention
  • spontaneous rectal bleeding (more than a spot on toilet paper)
  • gingival bleeding lasting longer than 5 min
  • any other bleeding event considered clinically relevant by the investigator

Minor bleeding events were defined as all other bleeding events that did not fulfil the criteria from above.
First administration until 31-38 days

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

November 1, 2004

Primary Completion (Actual)

July 1, 2006

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimate)

September 15, 2005

Study Record Updates

Last Update Posted (Estimate)

May 19, 2014

Last Update Submitted That Met QC Criteria

May 8, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1160.48
  • 2004-001988-21 (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.

Clinical Trials on Thromboembolism

Clinical Trials on enoxaparin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mozambique

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe