RE-MODEL Dabigatran Etexilate 150mg or 220mg Once Daily (o.d.) Versus (v.s.) Enoxaparin 40mg o.d. for Prevention of Thrombosis After Knee Surgery

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00168805
First received: September 12, 2005
Last updated: May 8, 2014
Last verified: February 2014
  Purpose

A phase III, randomised, parallel-group, double-blind, active controlled study to investigate the ef ficacy and safety of two different dose regimens of orally administered dabigatran etexilate capsule s [150 or 220 mg once daily starting with a half dose (i.e.75 or 110 mg) on the day of surgery] comp ared to subcutaneous enoxaparin 40 mg once daily for 6 to 10 days, in prevention of venous thromboem bolism in patients with primary elective total knee replacement surgery. RE-MODEL (Thromboembolism prevention after knee surgery)


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: RE-MODEL (Thromboembolism Prevention After Knee Surgery). Two Different Dose Regimens of Orally Administered Dabigatran Etexilate Capsules [150 or 220 mg Once Daily Starting With a Half Dose (i.e.75 or 110 mg) on the Day of Surgery] Compared to Subcutaneous Enoxaparin 40 mg Once Daily for 6-10 Days

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: First administration until 6-10 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:
  • Number of Participants With Major Venous Thromboembolic Event and Venous Thromboembolic Event-related Mortality During Treatment Period [ Time Frame: First administration until 6-10 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

  • Number of Participants With Proximal Deep Vein Thrombosis During Treatment Period [ Time Frame: First administration until 6-10 days ] [ Designated as safety issue: No ]
    Proximal Deep Vein Thrombosis as adjudicated by the VTE events committee

  • Number of Participants With Total Deep Vein Thrombosis During Treatment Period [ Time Frame: First administration until 6-10 days ] [ Designated as safety issue: No ]
    Total Deep Vein Thrombosis as adjudicated by the VTE events committee

  • Number of Participants With Symptomatic Deep Vein Thrombosis During Treatment Period [ Time Frame: First administration until 6-10 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

  • Number of Participants With Pulmonary Embolism During Treatment Period [ Time Frame: First administration until 6-10 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

  • Number of Participants Who Died During Treatment Period [ Time Frame: First administration until 6-10 days ] [ Designated as safety issue: No ]
    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 ] [ 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 6-10 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: 2101
Study Start Date: November 2004
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: dabigatran etexilate 220 mg
220 mg once daily
Drug: dabigatran etexilate
220 mg once daily
Experimental: dabigatran etexilate 150 mg
150 mg once daily
Drug: dabigatran etexilate
150 mg once daily
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, elect ive total knee 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, arteriovenous (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 aspartate aminotransferase (AST) or alanine transaminase (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 pote ntial and are not practising or do not plan to continue practising acceptable me thods of birth control
  • Allergy to radio opaque contrast media or iodine, heparins (incl. heparin indu ced 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: NCT00168805

  Show 105 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: NCT00168805     History of Changes
Other Study ID Numbers: 1160.25, 2004-001317-34
Study First Received: September 12, 2005
Results First Received: November 18, 2010
Last Updated: May 8, 2014
Health Authority: Australia:
Austria:
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Czech Republic:
Denmark:
Finland:
France: Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS)
Germany:
Hungary:
Italy: Comitato di Bioetica IRCCS Policlinico San Matteo Viale Golgi, 19 - 27100 PAVIA
Netherlands:
Poland:
South Africa:
Spain:
Sweden:

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

ClinicalTrials.gov processed this record on September 16, 2014