Creager 2008.

Study characteristics
Methods	Study design: double‐blind, randomised Country: USA Setting: 32 centres Intention‐to‐treat: yes
Participants	Number of participants randomly assigned: 430 Number of participants analysed: 370 Exclusions postrandomisation: 0 Losses to follow‐up: 60 Age (mean): 67 years Sex: male:female: 349:81 Inclusion criteria: aged ≥ 40 years; Fontaine stage II; stable claudication for ≥ 3 months despite standard care; ACD 50–800 m; ABI ≤ 0.90 in symptomatic leg and > 20% fall in ABI within 1 minute following cessation of exercise; in non‐compressible vessels, toe‐brachial index at rest < 0.70; final inclusion criteria after run‐in phase: ACD within 20% of ACD on previous measurements before run‐in phase; compliance with drug of 80–120% Exclusion criteria: ischaemic rest pain, ulcers, gangrene (Fontaine stage III and IV); evidence of non‐atherosclerotic PAD; peripheral neuropathy impairing walking; revascularisation procedures within preceding 3 months; sympathectomy within 6 months; type 1 diabetes mellitus; MI or major cardiac surgery within 3 months; unstable angina; heart failure; people receiving low molecular weight heparin and warfarin in combination with aspirin, or any other drug for IC
Interventions	Treatment: oral pentoxifylline, 400 mg tid Control: placebo Treatment 2: iloprost 50 µg bid Treatment 3: iloprost 100 µg bid Treatment 4: iloprost 150 µg bid Duration: 6 months
Outcomes	Primary: TWD expressed as % change from baseline to follow‐up Secondary: PFWD, QoL (WIQ and SF‐36), side effects
Notes	Treadmill protocol: 3.2 km/h at 0% gradient, increased by 2% every 2 minutes TWD expressed in metres at baseline and % change at follow‐up
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "randomised placebo controlled." Comment: no further information provided.
Allocation concealment (selection bias)	Unclear risk	Not mentioned.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Treatments appropriately blinded for participants and personnel.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not mentioned.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Unclear why participants stopped medication; unclear whether data presented represent intention‐to‐treat or per‐protocol analysis.
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement.
Other bias	Unclear risk	Sponsor: Berlex Pharmaceuticals Inc.