Aujesky 2011.

Methods	Design: international, open‐label, randomised, non‐inferiority trial. Multicentre study: 19 EDs in Switzerland, France, Belgium and the US. Period: February 2007 to June 2010. Sample size: justified (160 participants per treatment group would provide 80% power to detect a non‐inferiority margin of 4% using a 1‐sided α of 0.05, assuming a 5% drop‐out rate). Follow‐up: 90 days after randomisation.
Participants	344 eligible participants randomised, but only 339 included in primary analysis; 337 completed follow‐up and 317 were included in per‐protocol analysis. In the outpatient group (171 participants): 84 men, 87 women, mean age 47 years; inpatient group (168 participants): 85 men, 83 women, mean age 49 years. Inclusion criteria: aged ≥ 18 years with acute, symptomatic and objectively verified PE who were at low risk of death based on PESI (risk classes I or II). Exclusion criteria: arterial hypoxaemia, SBP < 100 mmHg, chest pain necessitating parenteral opioids, active bleeding, high risk of bleeding, gastrointestinal bleeding, severe renal failure, extreme obesity, history of HIT or allergy to heparins, therapeutic oral anticoagulation at the time of diagnosis of PE, pregnancy, diagnosis of PE > 23 hours before the time of screening.
Interventions	Outpatient (172 participants): subcutaneous enoxaparin 1 mg/kg twice daily and discharged from the ED within 24 hours of randomisation. If self injection was not possible, a study nurse either taught a caregiver to give the enoxaparin or arranged administration by a visiting nurse. Inpatient (172 participants): subcutaneous enoxaparin 1 mg/kg twice daily and admitted to hospital. All participants also received vitamin K antagonist therapy.
Outcomes	Primary outcome: recurrence of symptomatic confirmed VTE defined as recurrent PE or new or recurrent DVT within 90 days of randomisation. Secondary outcomes: overall satisfaction, major bleeding within 14 and 90 days of randomisation, all‐cause mortality within 90 days.
Notes	Diagnostic criteria for recurrent PE were a new intraluminal filling defect on spiral CT or pulmonary angiography or a new perfusion defect of a lung segment with corresponding normal ventilation by lung scan or confirmation of a new PE on autopsy. Diagnostic criteria for DVT were the non‐compressibility of a new venous segment or a substantial increase (≥ 4 mm) in the diameter of the thrombus during full compression in a previously abnormal segment on ultrasonography, or a new intraluminal filling defect on contrast venography. Overall satisfaction was assessed by a non‐validated 5‐point Likert scale questionnaire. Participants completed this questionnaire by telephone 14 days after randomisation. Major bleeding was defined as fatal bleeding, bleeding at critical sites (i.e. intracranial, intraspinal, intraocular, retroperitoneal, intra‐articular, pericardial or intramuscular with compartment syndrome), or bleeding with a reduction of haemoglobin of ≥ 20 g/L or resulting in transfusion of ≥ 2 units of packed red cells. Authors of the study declared they received grants, honoraria, consultancy fees, and payments from the pharmaceutical industry which sponsored the study. However, both regimens (outpatient or inpatient) patients received the same treatment.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The eligible patients were allocated to outpatient treatment or inpatient treatment groups in a one‐to‐one ratio with a randomised block design generated from a password protected computer web page.
Allocation concealment (selection bias)	Low risk	The patients were stratified by site and using small fixed block sizes (2 or 4). Quote: "To balance recruitment in time and preclude enrolment bias, the blocks varied randomly from two to four patients".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Although the paper says that the analysers were unmasked to treatment group assignment, there was a committee unaware of treatment assignment which confirmed all outcomes. Quote: "A committee of three clinical experts from the University Hospital of Lausanne (Switzerland) who were unaware of treatment assignment confirmed all outcomes and classified the cause of all deaths as definitely due to pulmonary embolism, possibly due to pulmonary embolism (e.g., sudden death without obvious cause), due to major bleeding, or due to another cause."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	< 20% in each group: outpatient group had 2 participants who did not complete follow‐up and inpatient group had 5 participants who did not complete follow‐up. The study authors were unable to confirm how many were alive.
Selective reporting (reporting bias)	Low risk	There is no evidence of selective reporting.
Other bias	Low risk	We did not find aspects of methodology that might be been influenced by vested interests and which may lead directly to a risk of bias.