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 - Full Text View

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:

MedlinePlus related topics: Knee Replacement

Drug Information available for: Dabigatran Dabigatran etexilate Enoxaparin sodium Dabigatran etexilate mesylate

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:

Number of Participants With Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period [ Time Frame: 6 - 10 days ] [ Designated as safety issue: Yes ]
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 scintagraphy, 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: 6 - 10 days ] [ Designated as safety issue: Yes ]
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: 6 - 10 days ] [ Designated as safety issue: Yes ]
Proximal Deep Vein Thrombosis as adjudicated by the VTE events committee
Number of Participants With Total Deep Vein Thrombosis During Treatment Period [ Time Frame: 6 - 10 days ] [ Designated as safety issue: Yes ]
Total Deep Vein Thrombosis as adjudicated by the VTE events committee
Number of Participants With Symptomatic Deep Vein Thrombosis During Treatment Period [ Time Frame: 6 - 10 days ] [ Designated as safety issue: Yes ]
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: 6 - 10 days ] [ Designated as safety issue: Yes ]
Pulmonary embolism confirmed by pulmonary V-Q scintagraphy, 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: 6 - 10 days ] [ Designated as safety issue: Yes ]
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: Yes ]
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 scintagraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy).
Number of Participants With Major Bleeding Events During Treatment Period [ Time Frame: 6 - 10 days ] [ Designated as safety issue: Yes ]
Major bleeding events were defined according to the modified McMaster criteria, and were adjudicated by a bleed adjudication committee. The bleeding event had to fulfil at least one of the following criteria in order to be classified as major:-
- 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

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00168805

Show 105 Study Locations

Sponsors and Collaborators

Boehringer Ingelheim Pharmaceuticals

Investigators

Study Chair:

Boehringer Ingelheim

Boehringer Ingelheim Pharmaceuticals

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided

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:	July 10, 2012
Health Authority:	Australia: Austria: Belgium: Federal Agency for Medicines and Health Products 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
Enoxaparin
Anticoagulants

Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on May 19, 2013