Yokote 2011.

Methods	Randomised controlled trial
Participants	Total number of participants: 250 Number of participants allocated to each group: fondaparinux (FX) group: 85, enoxaparin (EN): 86, placebo group: 85 Number of participants excluded and/or lost to follow‐up: FX group: 1, EN group: 2, placebo group: 2 Inclusion: patients older than 20 years of age undergoing elective primary unilateral THR Exclusion: patients who had undergone bilateral and revision THR. Other exclusion criteria included long‐term anticoagulation treatment such as unfractionated heparin, LMWH, vitamin K antagonists and antiplatelet agents for pre‐existing cardiac or cerebrovascular disease; history of VTE; coagulation disorder including antiphospholipid syndrome; presence of a solid malignant tumour or a peptic ulcer; and major surgery in the preceding 3 months. The study also excluded Caucasian patients.
Interventions	FX: postoperative sc injections of fondaparinux (2.5 mg once daily) for 10 consecutive days EN: postoperative sc injections of enoxaparin (40 mg or 20 mg twice daily) for 10 consecutive days Placebo: placebo (0.5 mL of isotonic saline) for 10 consecutive days The first postoperative injections of fondaparinux, enoxaparin and saline took place at an average of 18 hours (SD 2), 17 hours (SD 2) and 18 hours (SD 2), respectively, after the operation.
Outcomes	Primary efficacy outcome: incidence of DVT or VTE assessed by bilateral ultrasonographic studies from the external iliac vein to proximal portions of the calf veins at postoperative day 11. All scans were performed by experienced vascular technicians and were read by experienced radiologists who were blinded to participants' randomisation. Those with a negative scan were followed clinically for 12 weeks (until postoperative day 84) for signs or symptoms of DVT, pulmonary emboli or readmission to hospital because of a complication related to the chemical prophylaxis, a bleeding complication, a wound problem or any other clinical event. Participants who were found to have a distal (calf) DVT did not receive any chemical treatment. Those with proximal DVT received anticoagulant therapy, with initial administration of unfractionated heparin along with initiation of warfarin therapy. Primary safety outcome: incidence of any bleeding, major or minor. This was assessed daily during the treatment period of 10 days and within 24 hours after completion or discontinuation of treatment. An episode of bleeding was classified as major if it was retroperitoneal, intracranial or intraocular, or if it was associated with death, transfusion of more than 2 units of packed red blood cells or whole blood (except autologous), a reduction in level of Hb > 2 g/dL or a serious or life‐threatening clinical event requiring medical intervention. Suspected intra‐abdominal or intracranial bleeding was confirmed by ultrasonography, CT or MRI. Minor episodes of bleeding were defined as those with at least 1 of the following features: epistaxis lasting longer than 5 minutes or requiring intervention, ecchymosis or haematoma with maximum size of > 5 cm, haematuria not associated with trauma from the urinary catheter, gastrointestinal haemorrhage not related to intubation or to passage of a nasogastric tube, wound haematoma or haemorrhagic wound complications not associated with major haemorrhage or subconjunctival haemorrhage, requiring cessation of medication.
Notes	Use of adjunctive anticoagulative methods: All participants received the same routine mechanical prophylaxis (intermittent pneumatic compression device and a thigh‐high elastic compression bandage) during and after operation. Used for sensitivity analysis
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	The study did not clearly describe what randomisation method was used. Comment: unclear
Allocation concealment (selection bias)	Unclear risk	The study did not clearly describe what randomisation method was used and whether a strategy was used to confirm allocation concealment. Comment: unclear
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	The study did not clearly describe blinding Comment: unclear
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "All the scans were performed by experienced vascular technicians and were read by experienced radiologists who were blinded to the patient’s randomisation" Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	Low risk	250 of 267 participants finished the study. Comment: low risk of bias
Selective reporting (reporting bias)	Low risk	All primary efficacy and safety outcomes listed in the Methods section were reported. Comment: low risk of bias
Other bias	Low risk	No risk of other bias was identified.

AE: adverse event.
 APTT: activated partial thromboplastin time.
 BI: bleeding index.
 BMI: body mass index.
 CG: control group.
 CUS: compression ultrasonography.
 DVT: deep vein thrombosis.
 EBL: estimated blood loss.
 IPC: intermittent pneumatic compression.
 EN: enoxaparin.
 FX: fondaparinux.
 HES: hydroxy ethyl starch.
 INR: international normalised ratio.
 LMWH: low molecular weight heparin.
 MRV: magnetic resonance venography.
 NYHA: New York Heart Association.
 PE: pulmonary embolism.
 PT: prothrombin time.
 PTT: partial thromboplastin time.
 SAE: serious adverse event.
 sc: subcutaneous.
 SFJ: sapheno‐femoral junction.
 SVT: superficial venous thrombosis.
 THR: total hip replacement.
 TKA: total knee arthroplasty.
 TKR: total knee replacement.
 VTE: venous thromboembolism.