Columbus 1997.

Methods	Study design: randomised controlled trial. Method of randomisation: stratified according to whether the participant presented with DVT only or with PE, according to clinical centre. Concealment of allocation: not blinded for treatment allocation, blinded for outcome assessment. Exclusions post‐randomisation: none. Lost to follow‐up: none.
Participants	Country: Netherlands, France, Italy, Germany, Spain, Australia, New Zealand, Canada. Setting: hospital. No.: 1021 participants. Age: mean 60. Sex: 525 males. Inclusion criteria: acute symptomatic DVT and/or PE requiring antithrombotic therapy. DVT documented by ultrasonography or venography and PE by ventilation‐perfusion lung scanning (high probability of PE), pulmonary angiography or, if lung scanning was non‐diagnostic, by demonstrating DVT by compression ultrasonography or venography. Exclusion criteria: therapeutic doses of LMWH, UFH or oral anticoagulant therapy for more than 24 hours; contraindications for anticoagulant therapy; planned thrombolytic therapy; gastrointestinal bleeding in the preceding 14 days; surgery requiring anaesthesia within the previous 3 days; a stroke in the preceding 10 days; platelet count < 100,000/mm³ ; weight < 35 kg; pregnant or of childbearing potential and not using adequate contraception; in a location that made follow‐up difficult.
Interventions	Treatment: LMWH: Reviparin sodium (Clivarin, Knoll, Luwigshafen, Germany) in body weight adjusted fixed‐dose, s.c., twice daily. Decision to treat participants at home left to treating physician. Control: UFH: APTT‐adjusted dose, continuous i.v. infusion in hospital after initial intravenous bolus of 5000 IU. Treatment duration: at least 5 days; treatment cessation if INR was 2.0 or above for 2 consecutive days. Oral anticoagulation: started on first or second day and continued for a total of 12 weeks; INR 2.0 to 3.0.
Outcomes	Primary: symptomatic DVT or PE during initial treatment and within 12 weeks of randomisation. Secondary: major haemorrhage during initial treatment and within 12 weeks of randomisation; death within 12 weeks of randomisation.
Notes	Follow‐up: 12 weeks. DVT only: LMWH 372 (73%) and UFH 378 (74%). PE: 138 (27%) versus 133 (26%). In retrospect, 3 participants with DVT only and 2 with PE should have been excluded at entry as they did not have abnormal test results.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was performed with a computer algorithm.
Allocation concealment (selection bias)	Low risk	Central allocation by a 24‐hour telephone service.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Not blinded for treatment allocation. Comment: given the clinical outcomes of the study, review authors judged that the non‐blinding of the participants and staff was unlikely to have affected the outcomes.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Information on all suspected outcome events and deaths was reviewed and classified by a central adjudication committee whose members were unaware of the treatment assignments.
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcome data.
Selective reporting (reporting bias)	Low risk	The published report includes all expected outcomes.
Other bias	Low risk	The study appears to be free of other sources of bias.