Dabigatran Etexilate in Extended Venous Thromboembolism (VTE) Prevention After Hip Replacement Surgery - Full Text View

Sponsor:	Boehringer Ingelheim Pharmaceuticals
Information provided by:	Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00168818

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 III

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:

MedlinePlus related topics: Hip Replacement

Drug Information available for: Dabigatran Dabigatran etexilate Enoxaparin Sodium

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:

Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period [ Time Frame: 28 - 35 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:

Major Venous Thromboembolic Event and Venous Thromboembolic Event-related Mortality During Treatment Period [ Time Frame: 28 - 35 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
Proximal Deep Vein Thrombosis During Treatment Period [ Time Frame: 28 - 35 days ] [ Designated as safety issue: Yes ]
Proximal Deep Vein Thrombosis as adjudicated by the VTE events committee
Total Deep Vein Thrombosis During Treatment Period [ Time Frame: 28 - 35 days ] [ Designated as safety issue: Yes ]
Total Deep Vein Thrombosis as adjudicated by the VTE events committee
Symptomatic Deep Vein Thrombosis During Treatment Period [ Time Frame: 28 - 35 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
Pulmonary Embolism During Treatment Period [ Time Frame: 28 - 35 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
Death During Treatment Period [ Time Frame: 28 - 35 days ] [ Designated as safety issue: Yes ]
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: 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).
Major Bleeding Events During Treatment Period [ Time Frame: 28 - 35 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:	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

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

Show 116 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 by Boehringer Ingelheim Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Prins MH, Hettiarachchi R, Hantel S, Schnee J, Buller HR; RE-NOVATE Study Group. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet. 2007 Sep 15;370(9591):949-56.

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:	January 17, 2011
Health Authority:	Australia: Therapeutic Goods Administration; Austria:; Belgium: Federal Agency for Medicines and Health Products; 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
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 February 12, 2012