RECORD 1 Trial.

Methods	Study design: Randomised, double‐blind trial Country: Multi‐country (27 countries) Setting: Multi‐centre; hospital and home; February 2006 to March 2007 Intention‐to‐treat: Yes, modified ITT and per‐protocol analysis For the purposes of our meta‐analyses we used the reported modified ITT population of participants that underwent surgery
Participants	Number randomised: Total n = 4541 (rivaroxaban n = 2266; enoxaparin n = 2275) Exclusions post randomisation: Total n = 1177 (rivaroxaban n = 580; enoxaparin n = 597); 57 rivaroxaban and 51 enoxaparin randomised but not included in safety analysis ‐ did not receive study drug but no further description; excluded from ITT if not treated and did not undergo surgery and had no suitable venograms (additional 523 rivaroxaban, 546 enoxaparin) Losses to follow up: No reports of loss‐to‐follow‐up Age mean years (range): Rivaroxaban 63.1 (18 ‐ 91); enoxaparin 63.3 (18 ‐ 93) Sex F %: Rivaroxaban 55.2%; enoxaparin 55.8% Inclusion criteria: Men and women 18 years or older; scheduled to undergo elective total hip replacement Exclusion criteria: Scheduled to undergo staged, bilateral hip arthroplasty; pregnant or breastfeeding; active bleeding or a high risk of bleeding; contraindication for prophylaxis with enoxaparin; conditions preventing bilateral venography; substantial liver disease; severe renal impairment; concomitant use of protease inhibitors for the treatment of HIV; planned intermittent pneumatic compression; requirement for anticoagulant therapy that could not be stopped
Interventions	Treatment 1: 10 mg rivaroxaban, orally, once daily beginning after surgery Control: 40 mg enoxaparin, subcutaneously, once daily beginning the evening before surgery Duration: 35 days (range 31 ‐ 39); mean duration 33.4 days in rivaroxaban and 33.7 in enoxaparin group ‐ venography took place
Outcomes	Primary: Composite DVT (symptomatic or detected by venography), non‐fatal PE or death from any cause at day 36 Secondary: Major VTE (proximal DVT, non‐fatal PE or death from VTE), major bleeding, DVT, symptomatic VTE, death, lab values and cardiovascular events Bleeding definitions: Major bleeding ‐ fatal, occurred in a critical organ (e.g., retroperitoneal, intracranial, intraocular, and intraspinal bleeding), or required reoperation or extrasurgical‐site bleeding that was clinically overt and was associated with a fall in the haemoglobin level of at least 2 g per decilitre or that required transfusion of 2 or more units of whole blood or packed cells
Notes	Funding: Bayer Healthcare and Johnson & Johnson: data collected and analysed by sponsors, steering committee designed and supervised, all authors contributing had access to all data and analysis and vouch for accuracy and completeness of data reported Method of VTE evaluation/confirmation: Mandatory bilateral venography the day after the last dose of the study drug
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation generated in permuted blocks and stratification according to centre by a central telephone system with a computer‐generated randomised list
Allocation concealment (selection bias)	Low risk	Use of telephone system and computer‐generated randomisation list
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Patients received study medication plus placebo tablets or injection
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcomes assessed by a central, blinded adjudication committee
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	57 rivaroxaban and 51 enoxaparin randomised but not included in safety analysis ‐ did not receive study drug but no reasons given why
Selective reporting (reporting bias)	Low risk	No protocol provided but all outcomes reported on
Other bias	Unclear risk	Data was collected and analysed by the sponsors: Bayer HealthCare and Johnson & Johnson