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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00657150
First Posted: April 14, 2008
Last Update Posted: July 2, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Boehringer Ingelheim
  Purpose
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.

Condition Intervention Phase
Venous Thromboembolism Drug: Enoxaparin Drug: Dabigatran etexilate Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Prevention
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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

  • 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

  • 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

  • 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

  • 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

  • Number of Participants Who Died During Treatment Period [ Time Frame: 28-35 days ]
    All cause death, as adjudicated by the VTE events committee

  • 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).

  • 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.


  • Blood Transfusion [ Time Frame: Day 1 ]
    Number of treated and operated patients with required blood transfusion on day of surgery.

  • Volume of Blood Loss [ Time Frame: Day 1 ]
    Volume of blood loss for treated and operated patients during surgery.

  • Laboratory Analyses [ Time Frame: First administration to end of study ]
    Frequency of patients with possible clinically significant abnormalities.


Enrollment: 2055
Study Start Date: March 2008
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00657150


  Show 108 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00657150     History of Changes
Other Study ID Numbers: 1160.64
2007-002630-11 ( EudraCT Number: EudraCT )
First Submitted: March 27, 2008
First Posted: April 14, 2008
Results First Submitted: November 18, 2010
Results First Posted: December 17, 2010
Last Update Posted: July 2, 2014
Last Verified: December 2013

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Dabigatran
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants