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

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00168818
First received: September 12, 2005
Last updated: May 8, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Thromboembolism
Arthroplasty, Replacement, Hip
Drug: dabigatran etexilate
Drug: enoxaparin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period [ Time Frame: First administration until 31-38 days ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Major Venous Thromboembolic Event and Venous Thromboembolic Event-related Mortality During Treatment Period [ Time Frame: First administration until 31-38 days ] [ Designated as safety issue: No ]
    Major Venous Thromboembolic Event (VTE) is defined as proximal DVT and PE, as adjudicated by the VTE events committee

  • Proximal Deep Vein Thrombosis During Treatment Period [ Time Frame: First administration until 31-38 days ] [ Designated as safety issue: No ]
    Proximal Deep Vein Thrombosis as adjudicated by the VTE events committee

  • Total Deep Vein Thrombosis During Treatment Period [ Time Frame: First administration until 31-38 days ] [ Designated as safety issue: No ]
    Total Deep Vein Thrombosis as adjudicated by the VTE events committee

  • Symptomatic Deep Vein Thrombosis During Treatment Period [ Time Frame: First administration until 31-38 days ] [ Designated as safety issue: No ]
    Symptomatic Deep Vein Thrombosis, confirmed by venous compression ultrasound, venography or autopsy, and as adjudicated by the VTE events committee

  • Pulmonary Embolism During Treatment Period [ Time Frame: First administration until 31-38 days ] [ Designated as safety issue: No ]
    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

  • Death During Treatment Period [ Time Frame: First administration until 31-38 days ] [ Designated as safety issue: No ]
    All cause death, as adjudicated by the VTE events committee

  • Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period [ Time Frame: end of treatment to day 91±7 ] [ Designated as safety issue: No ]
    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).

  • Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period [ Time Frame: First administration until 31-38 days ] [ Designated as safety issue: Yes ]

    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.


  • Blood Transfusion [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Blood transfusion for treated and operated patients on Day of surgery.

  • Volume of Blood Loss [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Volume of blood loss for treated and operated patients during surgery.

  • Laboratory Analyses [ Time Frame: First administration to end of study ] [ Designated as safety issue: No ]
    Frequency of patients with possible clinically significant abnormalities.


Enrollment: 3494
Study Start Date: November 2004
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Active Comparator: enoxaparin
40 mg once daily
Drug: enoxaparin
40 mg once daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00168818

  Show 116 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00168818     History of Changes
Other Study ID Numbers: 1160.48, 2004-001988-21
Study First Received: September 12, 2005
Results First Received: November 18, 2010
Last Updated: May 8, 2014
Health Authority: Australia: Therapeutic Goods Administration
Austria:
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Czech Republic: SUKL
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
France: Agence Francaise de Securite Sanitaire des Produits de Sante
Germany: Bundesamt fuer Strahlenschutz
Hungary:
Italy: Comitato di Bioetica IRCCS Policlinico San Matteo Viale Golgi, 19 - 27100 PAVIA
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Norway: Norwegian Medicines Agency
Poland: CEBK
South Africa: Medicines Control Council
Spain: Agencia Española de Medicamentos y Productos Santarios
Sweden: MPA

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Dabigatran
Enoxaparin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 27, 2014