As effective as warfarin for the treatment of DVT and PE1
Composite of fatal PE, symptomatic non-fatal PE, and/or DVT
(Primary efficacy endpoint: 34 vs. 32 events, HR: 1.05, 95% CI [0.65, 1.70])2
The protocol specified non-inferiority margin (2.75) for the HR was derived based on the upper limit
of the 95% CI of the historical warfarin effect.
PRADAXA retains at least 66.9% of the historical warfarin
effect, based on the primary composite endpoint.
Composite of fatal PE, symptomatic non-fatal PE, and/or DVT
(Primary efficacy endpoint: 34 vs. 30 events, HR: 1.13, 95% CI [0.69, 1.85])3
The protocol specified non-inferiority margin (2.75) for the HR was derived based on the upper limit
of the 95% CI of the historical warfarin effect.
PRADAXA retains at least 63.9% of the historical warfarin
effect, based on the primary composite endpoint.

RE-COVER® & RE‑COVER II™ CLINICAL TRIALS FOR THE TREATMENT OF DVT AND PE
RE-COVER® & RE-COVER II™
Pivotal, parallel, randomized, double-blind, active-controlled trials for treatment of DVT and PE

Trial objective1
To demonstrate non-inferiority of PRADAXA to warfarin based on the primary composite endpoint of fatal PE or symptomatic non-fatal PE and/or DVT. The protocol specified non-inferiority margin (2.75) for the HR was derived based on the upper limit of the 95% CI of the historical warfarin effect.
Methodology
Patients received 5-10 days of an approved parenteral anticoagulant therapy followed by 6 months of oral-only treatment. Warfarin was overlapped with parenteral therapy.1,2
RE-COVER® enrolled 2539 patients (30.9% of patients with symptomatic PE with or without DVT; 68.9% with symptomatic DVT only):2
- 2286 patients (90%) received LMWH for parenteral anticoagulation1
- 1274 received PRADAXA 150 mg BID and 1265 received warfarin (INR target range 2.0-3.0)1,2
- Patients randomized to warfarin had a mean percentage of time in the INR target range of 60%2
- Mean age was 54.7 years2
RE-COVER IITM enrolled 2568 patients (31.8% with symptomatic PE with or without DVT; 68.1% with symptomatic DVT only):3
- 2280 patients (89%) received LMWH for parenteral anticoagulation3
- 1279 received PRADAXA 150 mg BID and 1289 received warfarin (INR target range 2.0-3.0)2
- Patients randomized to warfarin had a mean percentage of time in the INR target range of 57%3
- Mean age was 54.9 years2
Median duration of treatment: 174 days.*2
*Oral-only treatment period; does not include treatment period with parenteral anticoagulant.2
References: 1. Schulman S, Kearon C, Kakkar AK; for the RE‑COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342-2352. 2. Pradaxa [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. 3. Schulman S, Kakkar AK, Goldhaber SZ; for the RE‑COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014;129(7):764-772.

Bleeding definitions in PRADAXA clinical trials
Major bleeds in the NVAF, DVT, and PE trials fulfilled 1 or more of the following criteria: fatal bleeding, bleeding associated with a reduction in hemoglobin of at least 2.0 g/dL or leading to a transfusion of at least 2 units of blood, or symptomatic bleeding in a critical area or organ (intraocular, intracranial, intraspinal or intramuscular with compartment syndrome, retroperitoneal bleeding, intra-articular bleeding, or pericardial bleeding).1-3
Major bleeds in the hip replacement surgery trials fulfilled 1 or more of the following criteria: fatal bleeding, bleeding associated with a reduction in hemoglobin of at least 2.0 g/dL or leading to a transfusion of 2 or more units of blood, requiring treatment cessation, or leading to re-operation, or symptomatic bleeding in a critical area or organ (intraocular, intracranial, intraspinal, or retroperitoneal).3
Intracranial bleeds in the RE‑LY® trial included intracerebral (hemorrhagic stroke), subarachnoid, and subdural bleeds.3
Fatal bleeds in the RE‑LY® trial were defined as major bleeds with investigator-reported fatal outcomes and deaths with primary cause from bleeding.3
Non-intracranial fatal bleeds in the RE‑LY® trial were defined as major bleeds and deaths with primary cause from bleeding but without symptomatic intracranial bleeds based on investigator's clinical assessment.3
Clinically relevant nonmajor bleeds in the DVT and PE trials fulfilled at least one of the following criteria: spontaneous skin hematoma of at least 25 cm2; spontaneous nose bleed of more than 5 minutes duration; macroscopic hematuria, either spontaneous or, if associated with an intervention, lasting more than 24 hours; spontaneous rectal bleeding (more than spotting on toilet paper); gingival bleeding for more than 5 minutes; bleeding leading to hospitalization and/or requiring surgical treatment; bleeding leading to a transfusion of less than 2 units of whole blood or red cells; or any other bleeding event considered clinically relevant by the investigator.4-6
Clinically relevant nonmajor bleeds in the hip replacement surgery trials were defined as: spontaneous skin hematoma of at least 25 cm2; wound hematoma of at least 100 cm2; epistaxis of more than 5 min; macroscopic hematuria, either spontaneous or, if associated with an intervention, lasting more than 24 hours; spontaneous rectal bleeding; gingival bleeding for more than 5 minutes; and any other bleeding event judged as clinically significant by the investigator.7-9
References: 1. Data on File. Boehringer Ingelheim Pharmaceuticals, Inc. 2. Connolly SJ, Wallentin L, Ezekowitz MD, et al. The long-term multicenter observational study of dabigatran treatment in patients with atrial fibrillation (RELY-ABLE) study. Circulation. 2013;128(3):237-243. 3. Pradaxa [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. 4. Schulman S, Kearon C, Kakkar AK, et al; for the RE‑COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24)(suppl):2342-2352. 5. Schulman S, Kearon C, Kakkar AK, et al; for the RE‑MEDY and the RE‑SONATE Trials Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013;368(8)(suppl):709-718. 6. Schulman S, Kakkar AK, Goldhaber SZ, et al; for the RE‑COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014;129(7)(suppl):764-772. 7. Eriksson BI, Dahl OE, Rosencher N, et al. Oral dabigatran etexilate versus enoxaparin for venous thromboembolism prevention after total hip arthroplasty: pooled analysis of two phase 3 randomized trials. Thromb J. 2015;13:36. 8. Erikkson BI, Dahl OE, Büller HR, et al; for the BISTRO II study group. A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial. Thromb Haemost. 2005;3:103-111. 9. The European Agency for the Evaluation of Medicinal Products. Guideline on clinical investigation of medicinal products for prevention of venous thromboembolism (VTE) in patients undergoing high VTE-risk surgery. CPMP/EWP/707/98 Rev. 1. 2007. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/05/WC500143764.pdf. Accessed 15 July 2016.