Otsuka Study 21‐86‐103.

Methods	Study design: single‐centre, randomised, double‐blind, placebo‐controlled Intention to treat: yes Country: USA
Participants	Number randomised: 33 (cilostazol n = 17; placebo n = 16) Age (mean years): cilostazol = 56; placebo = 59 Sex %M: cilostazol = 82%; placebo = 88% Inclusion criteria: Aged ≥ 21 years (both sexes); had atherosclerosis obliterans‐induced intermittent claudication which was chronic (at least 6 months), stable (6 months); evidence of peripheral occlusive arterial disease; ICD ≤ 100 m on a constant load treadmill (10% incline, 3.5km/h); less than 30% variation in ICD during lead‐in period Exclusion criteria: lower extremity ischaemic rest pain, severe ulceration or gangrene; female of childbearing potential; malignancy; cardiac valve disorder or replacement; clinically significant abnormal lab value pre‐treatment; renal insufficiency; a requirement for the uninterrupted use of platelet‐active or vasoactive drugs; use of an investigational drug within the past 30 days; diabetes mellitus: either insulin‐dependent or with duration > 5 years; status post vascular surgery, splenectomy, or gastrointestinal surgery within past 12 months
Interventions	Treatment: cilostazol 150 mg, twice daily, oral administration Control: placebo Duration: 21 weeks (from the text, change in ACD and ICD were measured and reported after 6 weeks)
Outcomes	Change in ACD and ICD (after 6 weeks of therapy), subjective claudication improvement as per patient, palpation of arterial pulses, doppler‐measured limb pressure, sitting arm blood pressure; measured at baseline and then weeks 6, 9, 13, 17 and 21
Notes	Immediate‐incline treadmill method: incline load started immediately at 10% and remained constant with speed constant at 3.2km/h Dosage of cilostazol described as "fixed 150 mg bid oral dose... formulated as 50 mg cilostazol tablets". Assumption is that authors meant tablets were taken three times daily Three‐week placebo lead‐in period
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient description of sequence generation methods
Allocation concealment (selection bias)	Unclear risk	Insufficient description of allocation concealment methods
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Although study used a placebo, there is insufficient description to determine if blinding is adequate
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Blinding of assessors is not adequately discussed
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Dropouts overlap without discussion
Selective reporting (reporting bias)	High risk	Subjective claudication improvement, palpitation of arterial pulses, doppler‐measured limb pressures and sitting arm blood pressure were not reported
Other bias	Unclear risk	Study supported by Otsuka America Pharmaceutical Inc