Merli 2001.

Methods	Study design: randomised controlled trial. Method of randomisation: block randomisation without stratification. Concealment of allocation: partly blinded for treatment allocation, blinded for outcome assessment. Exclusions post‐randomisation: not stated. Lost to follow‐up: not stated.
Participants	Country: Australia, Austria, Belgium, Denmark, France, Hungary, Ireland, Israel, Italy, Netherlands, Norway, Poland, Spain, Sweden, United Kingdom and USA. Setting: hospital. No.: 900 participants. Age: mean 61 years. Sex: 492 males. Inclusion criteria: symptomatic lower extremity DVT confirmed by venography or ultrasonography (if venography was inconclusive), symptomatic PE confirmed by high probability ventilation‐perfusion scanning or positive pulmonary angiography with confirmation of lower extremity DVT. All those who were eligible underwent baseline lung scanning or angiography. Exclusion criteria: more than 24 hours of previous treatment with heparin or warfarin; need for thrombolytic therapy; known haemorrhagic risk, including active haemorrhage, active intestinal ulcerative disease, known angiodysplasia or eye, spine or central nervous system surgery within the previous month; renal insufficiency (serum creatinine concentration > 180 µmol/litre (2.03 mg/dL)); severe hepatic insufficiency; allergy to heparin, protamine, porcine products, iodine or contrast media; history of heparin‐associated thrombocytopenia or heparin‐ or warfarin‐associated skin necrosis; treatment with other investigational therapeutic agents within the previous 4 weeks; inferior vena cava interruption; known pregnancy or lactation.
Interventions	Treatment: LMWH: enoxaparin weight‐adjusted s.c. dose (1.0 mg/kg of body weight twice daily or 1.5 mg/kg of body weight o.d.). Control: UFH: initial i.v. bolus injection followed by an infusion based on an approved nomogram. In general: 6 hours after initial bolus an adjusted dose was given to maintain APTT between 55 and 80 seconds. APTT was measured daily. Treatment duration: enoxaparin and heparin treatment were continued for at least 5 days, and warfarin was started within 72 hours of initial study drug administration. 43 participants received phenprocoumon in place of warfarin sodium. INR between 2.0 and 3.0. Oral anticoagulation: oral anticoagulation was continued for at least 3 months.
Outcomes	Primary: worsening or recurrence of DVT or PE within 3 months. Secondary: clinical overt minor or major haemorrhage.
Notes	Participants who received LMWH (2 groups; o.d. and twice daily) were analysed as 1 group.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The authors refer to a random number table.
Allocation concealment (selection bias)	Low risk	The randomisation numbers were affixed to sealed treatment kits.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Partly 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	The Outcome Adjudication Committee provided blinded outcome assessments.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.
Selective reporting (reporting bias)	Low risk	Published report includes all expected outcomes.
Other bias	Low risk	The study appears to be free of other sources of bias.