Phase III Study Testing Efficacy & Safety of Oral Dabigatran Etexilate vs Warfarin for 6 m Treatment for Acute Symp Venous Thromboembolism (VTE) - Full Text View

Purpose

The general aim of this study is to determine the comparative safety and efficacy of dabigatran etexilate 150 mg bid administered orally and warfarin Pro re nata (As needed/PRN) to maintain an International Normalised Ratio (INR) of 2.0-3.0 for 6 month treatment of acute symptomatic VTE.

The primary objective is to investigate the efficacy of dabigatran compared to warfarin during the 6 month treatment period. The investigation of other selected efficacy aspects and safety are regarded as secondary objective of this trial.

Condition	Intervention	Phase
Thromboembolism	Drug: Warfarin 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: Treatment
Official Title:	A Phase III, Randomised, Double Blind, Parallel-group Study of the Efficacy and Safety of Oral Dabigatran Etexilate (150 mg Bid) Compared to Warfarin (INR 2.0-3.0) for 6 Month Treatment of Acute Symptomatic Venous Thromboembolism, Following Initial Treatment (5-10 Days) With a Parenteral Anticoagulant Approved for This Indication

Resource links provided by NLM:

MedlinePlus related topics: Blood Thinners Deep Vein Thrombosis

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

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:

Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE [ Time Frame: For statistical analysis 1: from randomisation to end of post treatment period (ptp), planned to be up to day 224. For statistical analysis 2: from randomisation to 6 months (up to day 180) ] [ Designated as safety issue: No ]
All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.

Secondary Outcome Measures:

Number of Participants With Recurrent Symptomatic VTE and All Deaths [ Time Frame: For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. ] [ Designated as safety issue: No ]
VTE or any death which occured from randomisation to end of ptp. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
Number of Participants With Recurrent Symptomatic DVT [ Time Frame: For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. ] [ Designated as safety issue: No ]
Symptomatic DVT which occured from randomisation to end of ptp. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
Number of Participants With Recurrent Symptomatic Non-fatal PE [ Time Frame: For statistical analysis 1: from randomisation to 6 months (up to day 180). For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. ] [ Designated as safety issue: No ]
Symptomatic non-fatal PE which occured from randomisation to end of ptp. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
Number of Participants Who Died Due to VTE [ Time Frame: From randomisation to 6 months (up to day 180) and to end of ptp (planned to be up to day 224) ] [ Designated as safety issue: No ]
VTE - related deaths which occured from randomisation to end of ptp. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
Number of Participants Who Died (Any Cause) [ Time Frame: For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. ] [ Designated as safety issue: No ]
Any deaths which occured from randomisation to end of ptp. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
Number of Participants With Major Bleeding Events (MBE) [ Time Frame: From first intake of study drug to last intake of study drug + 6 days ] [ Designated as safety issue: Yes ]
MBEs defined as per the recommendations of the International Society on Thrombosis and Haemostasis. A bleeding event was categorised as an MBE (adjudicated by the independent central assessment committee) if it fulfilled at least one of the following criteria:

Ã¢â "Â Fatal bleeding, Ã¢â "Â Symptomatic bleeding in a critical area or organ, Ã¢â "Â Bleeding causing a fall in haemoglobin level of 20 g/L (1.24 mmol/L) or more, or leading to transfusion of 2 or more units of whole blood or red cells.

Other Outcome Measures:

Number of Participants With Acute Coronary Syndrome (ACS) [ Time Frame: From first intake of study drug to last contact date ] [ Designated as safety issue: Yes ]
Any ACS occurring during the conduct of the study (centrally adjudicated as definite). Patients having a centrally adjudicated definite ACS during intake of study drug and after stopping study drug, according to treatment group. ACS assessments pre-specified in the protocol without adjudication. Prior to database lock, the steering committee asked to have ACS events adjudicated by an independent committee. After database lock, the committee was provided with source documentation that was blinded to the patient's treatment assignment. ACS results presented are based on adjudication findings.

Enrollment:	2589
Study Start Date:	April 2008
Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Dabigatran etexilate (150mg bid) Patients will receive 1 capsule containing 150 mg dabigatran etexilate/matching placebo twice daily	Drug: Dabigatran etexilate 150mg bid
Active Comparator: Warfarin (INR 2.0-3.0) Patients will receive tablets PRN warfarin/matching placebo to maintain a target INR of 2.0-3.0	Drug: Warfarin PRN (to maintain a target INR of 2.0-3.0)

Eligibility

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

Criteria

Inclusion criteria:

Acute symptomatic uni- or bilateral Deep Vein Thrombosis (DVT) of the leg involving proximal veins, and/or Pulmonary Embolism (PE)
Male or female, being 18 years of age or older
Written informed consent for study participation

Exclusion criteria:

Persistent symptoms of VTE
PE requiring urgent intervention
Use of vena cava filter
Contraindications to anticoagulant therapy
Allergy to study medications
Elevated Aspartate-aminotransferase (AST) or Alanine-aminotransferase (ALT) > 3x Upper Limit of Normal (ULN) or known liver disease expected to have an impact on survival
Severe renal impairment
Patients considered unsuitable for inclusion

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00680186

Show 220 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 Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00680186 History of Changes
Other Study ID Numbers:	1160.46, 2007-002631-86
Study First Received:	May 16, 2008
Results First Received:	May 4, 2012
Last Updated:	September 12, 2012
Health Authority:	Australia: Dept of Health and Ageing Therapeutic Goods Admin Brazil: National Health Surveillance Agency Bulgaria: Bulgarian Drug Agency, BG-1504 Sofia Canada: Health Canada, Therapeutic Products Directorate China: Food and Drug Administration Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10 Denmark: Danish Medicines Agency France: AFSSAPS Great Britain: MHRA Hungary: National Institute of Pharmacy, H-1051 Budapest India: Drugs Controller General of India Israel: Israeli Health Ministry Pharmaceutical Administration Italy: Ethics Committee Korea, Republic of: Korea Drug and Food Administration Malaysia: National Pharmaceutical Control Bureau Netherlands: Central Committee Research Involving Human Subjects New Zealand: Multicentre Ethics Committee/Medsafe Norway: Norwegian Medicines Agency (Statens Legemiddelverk) Philippines: Department of Health Poland: Registration Medicinal Product Medical Device Biocidal Product Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow Singapore: Health Sciences Authority,Ministry of Health Slovakia: SUKL (state institute for drug control), SK-825 08 Bratislava 26 South Africa: MCC (Medicines Control Council) Spain: Agencia Española de Medicamentos y Productos Sanitarios Sweden: Medical Products Agency Taiwan: Department of Health Thailand: Ministry of Public Health Turkey: Ministry of Health Central Ethics Committee Ukraine: Ministry of Health Care of Ukraine (MoH of Ukraine) United States: Food and Drug Administration

Additional relevant MeSH terms:

Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases

Thrombosis
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013