SACRE Study.

Methods	Study design: Randomised trial Country: France Setting: Multicentre (65 centres); hospital and home; September 1997 to October 1999 Intention‐to‐treat: Yes, and per‐protocol For the purposes of our meta‐analyses we used the reported ITT population
Participants	Number randomised: Total n = 1289 (LMWH n = 644; anticoagulant n = 645) Exclusions post randomisation: Total n = 10 (LMWH n = 1; anticoagulant n = 9); no treatment 7 (1 reviparin, 6 acenocoumarol); event at randomisation: 3 acenocoumarol Losses to follow up: Not reported Age mean years (SD): LMWH 66 (11); anticoagulant 65 (12) Sex %F: LMWH 51%; anticoagulant 50% Inclusion criteria: 18 years or older; scheduled to undergo elective unilateral primary total hip replacement Exclusion criteria: Femoral neck fracture; current active bleeding or disorders contraindicating anticoagulant therapy; a history of DVT or PE; heparin‐induced thrombocytopaenia, peptic ulcer, allergy to radiopaque contrast medium; use of aspirin or ticlopidine hydrochloride; renal insufficiency; liver failure; acute endocarditis; recent stroke; uncontrolled hypertension; pregnancy; alcoholism; inability to follow instructions
Interventions	Treatment: Fixed‐dose subcutaneous LMWH reviparin sodium, 4200 anti‐Xa IU, beginning 12 hours preoperatively Treatment 2: After initial LMWH treatment as described above, crossed over to adjusted‐dose oral anticoagulant acenocoumarol, international normalised ratio, 2 ‐ 3 Duration: 6 weeks after surgery
Outcomes	Primary: Combined clinical events of symptomatic thromboembolic event, major haemorrhage or death Secondary: Minor bleeding Bleeding definitions: Major bleeding ‐ clinically overt and was associated with a decrease in haemoglobin level of more than 20 g/L or required a transfusion of 2 U or more of packed red blood cells after randomisation or was digestive, intracranial, retroperitoneal or intraocular or was located at the surgical site and required reoperation or, according to the investigator's opinion, led to discontinuation of the treatment. Minor bleeding ‐ clinically overt but not major
Notes	Funding: Supported by Knoll France, Investigators received USD 400 per patient included in the study and PI received final grant of USD 4000 Method of VTE evaluation/confirmation: Suspected DVT confirmed by venography or duplex scanning; suspected PE confirmed by ventilation‐perfusion or angiography
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"...randomized computer‐derived treatment schedule" performed at a central location, stratified by each centre, balanced in blocks of four
Allocation concealment (selection bias)	Low risk	Utilised a centralised computer‐derived randomisation schedule
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	No mention of blinding of participants or personnel; most likely unblinded as one treatment given subcutaneously and the other orally
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcomes interpreted by a blinded adjudication committee
Incomplete outcome data (attrition bias) All outcomes	Low risk	Table 1. clearly demonstrates missing participants and reasons, although it should be noted the anticoagulant treatment group had a higher rate of protocol violations (statistical tests not performed)
Selective reporting (reporting bias)	Low risk	All outcomes reported on
Other bias	Low risk	No indication of other bias