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Efficacy and Safety of Dabigatran Compared to Warfarin for 6 Month Treatment of Acute Symptomatic Venous Thromboembolism (RE-COVER I)

Primary Purpose

Thromboembolism

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

dabigatran etexilate 150 mg

warfarin (INR 2-3)

About this trial

This is an interventional treatment trial for Thromboembolism

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria Acute deep vein thrombosis (DVT) of the leg involving proximal veins, and/or pulmonary embolism (PE) iin patients for whom at least 6 months of anticoagulant therapy is considered appropriate Male or female, being 18 years of age or older Written informed consent for study participation Exclusion criteria Overt symptoms of VTE for longer than 2 weeks prior to enrolment PE satisfying at least one of the following criteria: Haemodynamic instability, embolectomy is indicated or performed, thrombolytic therapy is indicated or performed, or suspected source of PE is other than the legs Actual or anticipated use of vena cava filter Contraindications to anticoagulant therapy Patients who in the investigators opinion should not be treated with warfarin Allergy to heparins or other alternate approved therapy used for initial treatment, warfarin or dabigatran, or to one of the excipients included in these medications Patients who in the investigators judgement are perceived as having an excessive risk of bleeding Known anaemia Need of anticoagulant treatment for disorders other than VTE Recent unstable cardiovascular disease Elevated AST or ALT > 2x ULN Liver disease expected to have any potential impact on survival Patients who have developed transaminase elevations upon exposure to ximelagatran Severe renal impairment Women who are pregnant, nursing, or of childbearing potential who refuse to use a medically acceptable form of contraception Participation in another clinical trial with an investigational drug during the last 30 days or previous participation in this study Patients considered unsuitable for inclusion by the investigator

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

dabigatran etexilate 150 mg

warfarin (INR 2-3)

Arm Description

twice daily

prn to maintain INR (2-3)

Outcomes

Primary Outcome Measures

Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE

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

VTE or any death which occured from randomisation to end of post treatment period. 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

Symptomatic DVT which occured from randomisation to end of post treatment period. 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

Symptomatic non-fatal PE which occured from randomisation to end of post treatment period. 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

VTE - related deaths which occured from randomisation to end of post treatment period. 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)

Any deaths which occured from randomisation to end of post treatment period. 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 Bleeding Events

Major bleeding events (MBE) were defined as Fatal bleeding Symptomatic bleeding in a critical area or organ 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 Clinically-relevant bleeding events (CRBE) was defined as spontaneous skin hematoma >=25 cm² spontaneous nose bleed >5 min macroscopic hematuria spontaneous or >24 hours if associated with an intervention spontaneous rectal bleeding (more than spotting on toilet paper) gingival bleeding >5 min leading to hospitalisation and / or requiring surgical treatment leading to a transfusion of <2 units of whole blood or red cells any other bleeding event considered clinically relevant by the investigator Any bleeding events were defined as major, clinically-relevant and nuisance bleeding events. Nuisance bleeding events were defined as all other bleeding events that did not fulfil the criteria from above.

Number of Participants With Acute Coronary Syndrome (ACS)

Any ACS occurring during the conduct of the study (centrally adjudicated as definite). Counts of patients having a centrally adjudicated definite ACS during intake of active study drug, after stopping active study drug and before or without intake of active study drug, according to treatment group. 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.

Laboratory Analyses

Frequency of patients with possible clinically significant abnormalities.

Full Information

NCT ID

NCT00291330

First Posted

February 13, 2006

Last Updated

June 3, 2014

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT00291330

Brief Title

Efficacy and Safety of Dabigatran Compared to Warfarin for 6 Month Treatment of Acute Symptomatic Venous Thromboembolism

Acronym

RE-COVER I

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2014

Overall Recruitment Status

Completed

Study Start Date

February 2006 (undefined)

Primary Completion Date

May 2009 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. Study Description

Brief Summary

The purpose of this trial is to determine the comparative safety and efficacy of dabigatran etexilate 150 mg bid administered orally and warfarin as needed (pro re nata - prn) to maintain an International Normalised Ratio (INR) of 2.0-3.0 for 6 month treatment of acute symptomatic venous thromboembolism (VTE), following initial treatment (5-10 days) with a parenteral anticoagulant approved for this indication. This trial aims to demonstrate non-inferiority of dabigatran compared with warfarin in patients with acute symptomatic VTE. After achieving non-inferiority, this trial also aims to establish superiority (by means of hierarchical tests) of dabigatran over warfarin.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thromboembolism

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

Double

Allocation

Randomized

Enrollment

2564 (Actual)

8. Arms, Groups, and Interventions

Arm Title

dabigatran etexilate 150 mg

Arm Type

Experimental

Arm Description

twice daily

Arm Title

warfarin (INR 2-3)

Arm Type

Active Comparator

Arm Description

prn to maintain INR (2-3)

Intervention Type

Drug

Intervention Name(s)

dabigatran etexilate 150 mg

Intervention Description

twice daily

Intervention Type

Drug

Intervention Name(s)

warfarin (INR 2-3)

Intervention Description

prn to maintain INR (2-3)

Primary Outcome Measure Information:

Title

Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE

Description

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)

Secondary Outcome Measure Information:

Title

Number of Participants With Recurrent Symptomatic VTE and All Deaths

Description

Time Frame