Esato 1995.

Study characteristics
Methods	Study design: RCT parallel group
Participants	Country: Japan Nº patients: 135, 46 with Buerger's disease (21 in clinprost group and 25 in alprostadil group) Setting: not stated Mean age: 61.5 years Gender: not described Inclusion criteria: patients with Buerger's disease and ischaemic ulcer < 1 year or rest pain Exclusion criteria: patients with previous lower limb revascularisation surgery or sympathectomy; contra‐indications for prostaglandin use
Interventions	Treatment: Clinprost group: Lipidious emulsion of TTC‐909 (clinprost, a prostacyclin analogue): 2 ampoules (1 ampoule with TTC‐909 with 1 mL plus 1 ampoule of Lipo PGE1 placebo with 2 mL) completed with saline solution, resulting in 10 mL of solution applied daily, a total dose of 2 mcg, intravenously Alprostadil group: Lipidious emulsion with PGE 1 (alprostadil), 2 ampoules (1 ampoule with Lipo PGE1 with 2 mL plus 1 ampoule of TTC‐909 placebo with 1 mL) completed with saline solution, resulting in 10 mL of solution applied daily, a total dose of 10 mcg, intravenously Duration of treatment: 4 weeks No follow‐up
Outcomes	Primary: improvement of rest pain and ischaemic ulcer Secondary: safety
Notes	Conflict of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Stated, but did not describe methods
Allocation concealment (selection bias)	Unclear risk	Information not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Doctor responsible for outcome assessment assessed the patients at the start and at the end of treatment, but was not responsible for drug administration
Incomplete outcome data (attrition bias) All outcomes	High risk	Adoption of "as‐treated" (per protocol) analyses
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	High risk	Absence of patient's smoking history