Breddin 2001.

Methods	Study design: randomised controlled trial. Method of randomisation: stratified according to site. Concealment of allocation: not blinded for treatment allocation, blinded for outcome assessment. Exclusions post‐randomisation: none. Lost to follow‐up: none.
Participants	Country: Argentina, Austria, Czech Republic, Denmark, Germany, Hungary, Israel, Poland, Norway, United Kingdom. Setting: hospital. No.: 1137 participants. Age: mean 58 years. Sex: 621 males. Inclusion criteria: acute DVT confirmed by venography without symptoms lasting longer than 14 days. Exclusion criteria: presence of thrombi only in isolated calf veins or isolated muscle veins; clinically symptomatic PE; treatment with UFH, LMWH, or VKA for 24 hours or more before enrolment; uncontrolled hypertension; stroke within 3 weeks of enrolment; cerebral vascular aneurysm or active gastroduodenal ulcer; bacterial endocarditis; thrombocytopenia (< 100,000 platelets/mm³; severe liver or renal insufficiency; receipt of spinal or epidural anaesthesia or lumbar puncture in the 5 days before enrolment; surgery in the 5 days before enrolment; concomitant treatment with fibrinolytic agents or platelet function inhibitors; a body weight of less than 35 kg; pregnancy and known drug abuse.
Interventions	Treatment: LMWH: Reviparin (Clivarin, Knoll, Ludwigshafen, Germany) twice daily, body weight adjusted (7000 anti‐factor Xa IU for a weight of 35 to 45 kg, 8400 IU for 46 to 60 kg and 12,600 IU for more than 60 kg). Control: 5000 IU i.v. UFH plus continuous i.v. infusion of 1250 IU/hour (dose‐adjusted APTT × 1.5 to 2.5. Treatment duration: LMWH 5 to 7 days, UFH until INR > 2.0 (and maintained). Oral anticoagulation: in both groups (started day 1) for 90 days.
Outcomes	Primary: change in venographically determined thrombus size (Marder's score) between base line and day 21 (± 2 days). Secondary: Clinical outcomes: recurrent DVT or PE during initial treatment and 3 months' follow‐up; major haemorrhagic events between day 0 and 21.
Notes	Follow‐up: 90 days. LMWH once daily group (374 participants) not included in analysis because LMWH was given for 28 days.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information.
Allocation concealment (selection bias)	Unclear risk	Insufficient information.
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	Blinded assessment of outcomes.
Incomplete outcome data (attrition bias) All outcomes	High risk	Reasons for missing second venogram and therefore exclusion for efficacy analysis are not provided and missing outcome data imbalanced in numbers across intervention groups.
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.