RECORD 2 Trial.

Methods	Study design: Randomised, double‐blind, controlled trial Country: Multinational (21 countries) Setting: Multicentre (123 centres); hospital and home; February 2006 to April 2007 Intention‐to‐treat: Modified ITT: not‐treated, did not receive surgery, no readable venogram For the purposes of our meta‐analyses we used the reported modified ITT population of participants that underwent surgery
Participants	Number randomised: Total n = 2509 (rivaroxaban n = 1252; enoxaparin n = 1257) Exclusions post randomisation: Total n = 90 (rivaroxaban n = 40; enoxaparin n = 50). Rivaroxaban: 24, enoxaparin: 28 ‐ not taken study medication (no reason why); rivaroxaban 16 and enoxaparin 22 did not receive surgery Losses to follow up: Not reported Age mean years (SD): Rivaroxaban 61.4 (13.2); enoxaparin 61.6 (13.7) Sex %F: Rivaroxaban 54.3% enoxaparin 53.0% Inclusion criteria: Aged 18 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; use of fibrinolytic therapy; planned intermittent pneumatic compression; requirement for anticoagulant therapy that could not be stopped
Interventions	Treatment: 10 mg rivaroxaban, orally, once daily beginning after surgery plus placebo injections for 10 ‐ 14 days Control: 40 mg enoxaparin, subcutaneously, once daily beginning the evening before surgery and continued for 10 ‐ 14 days and received placebo tablets for the entire study period Duration: 31 ‐ 39 days
Outcomes	Primary: Composite of any DVT, nonfatal PE and all‐cause mortality; incidence of major bleeding events Secondary: Major VTE (composite of proximal DVT, non‐fatal PE and VTE‐related death); DVT (proximal and distal), symptomatic VTE, on‐treatment bleeding, death 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 AG, Johnson & Johnson Pharmaceutical Research and Development LLC; sponsors involved in design and conduct of trial, data collection and analysis; all authors had full access to data and analyses and vouch for accuracy and completeness of data and were involved in decision to submit the manuscript Method of VTE evaluation/confirmation: DVT confirmed by bilateral venography; PE confirmed by perfusion/ventilation lung scintigraphy, angiography, chest X‐ray or spiral CT or autopsy
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	All participants were accounted for, with similar numbers in each treatment group, but no description was given for excluded participants that did not take study medication
Selective reporting (reporting bias)	Low risk	No protocol provided but all outcomes reported on
Other bias	Unclear risk	Funded by Bayer HealthCare and Johnson & Johnson ‐ study sponsors were involved in the design and conduct of the trial. The data were collected and analysed by the sponsors of the study