RE‐COVER II.
| Methods |
Study design: randomised, double‐blind, double‐dummy trial Duration of study: 6 months |
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| Participants |
Setting: 208 study sites Country: 31 countries worldwide No: 2568: dabigatran 1280, warfarin 1288 Age, mean (SD) years: dabigatran 54.7 (16.2) years, warfarin 55.1 (16.3) years Sex: dabigatran 781 M/499 F, warfarin 776 M/512 F Inclusion criteria: patients aged 18 or older who had acute, symptomatic, objectively verified proximal deep vein thrombosis of the legs or pulmonary embolism and for whom 6 months of anticoagulant therapy was considered to be an appropriate treatment Exclusion criteria: duration of symptoms longer than 14 days; pulmonary embolism with haemodynamic instability or requiring thrombolytic therapy; another indication for warfarin therapy; recent unstable cardiovascular disease; a high risk of bleeding; liver disease with an aminotransferase level that was 3 times the upper limit of the normal range; an estimated creatinine clearance of less than 20 mL per minute; a life expectancy of less than 6 months; a contraindication to heparin or to radiographic contrast material; pregnancy or risk of becoming pregnant; requirement for long‐term anticoagulant therapy |
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| Interventions |
Intervention 1: oral dabigatran 150 mg twice daily and warfarin‐like placebo for 6 months Intervention 2: active warfarin adjusted to achieve an INR of 2.0 to 3.0 and dabigatran‐like placebo for 6 months |
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| Outcomes |
Primary: recurrent VTE objectively verified, preferably with the same method as for the index event Secondary: major bleeding defined according to the International Society on Thrombosis and Haemostasis criteria |
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| Notes | — | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "Patients were randomised by use of an interactive voice response system and a computer‐generated randomisation scheme in blocks of 4" Comment: insufficient information to permit judgement of high or low risk |
| Allocation concealment (selection bias) | Low risk | Comment: no information given about how treatment allocation was concealed but study authors state that "the design of the trial was essentially identical to that of the first study with dabigatran for the treatment of acute VTE" (RE‐COVER), which we judged to be at low risk of selection bias |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "Double‐blind" Comment: stated as double‐blind. No other information given about how blinding was maintained but study authors state that "the design of the trial was essentially identical to that of the first study with dabigatran for the treatment of acute VTE", which we judged to be at low risk of performance bias |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "A central adjudication committee, the members of which were unaware of the treatment assignments, classified all suspected outcome events, bleeding events, and deaths" Comment: study judged to be at low risk of detection bias |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No missing outcome data |
| Selective reporting (reporting bias) | Low risk | All of the study's pre‐specified outcomes have been reported in the pre‐specified way |
| Other bias | Unclear risk | The study was funded by Boehringer‐Ingelheim, the pharmaceutical company that developed dabigatran. It is possible that this may have influenced the timeframe of reported safety outcomes. |
DVT: deep vein thrombosis F: female INR: international normalised ratio ITT: intention‐to‐treat LMWH: low molecular weight heparin M: male PE: pulmonary embolism SD: standard deviation ULN: upper limit of normal VKA: vitamin K antagonist VTE: venous thromboembolism