Otsuka Study 21‐86‐101.

Methods	Study design: single‐centre, randomised, double‐blind, placebo‐controlled Intention to treat: yes Country: USA
Participants	Number randomised: 53 (cilostazol n = 28; placebo n = 25) Age (mean years): cilostazol = 62; placebo = 58 Sex %M: cilostazol = 89%; placebo = 84% Inclusion criteria: Aged 21 to 70 (both sexes), had atherosclerosis obliterans‐induced intermittent claudication which was chronic (at least 6 months), stable (6 months); Evidence of PAOD; 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: limb‐threatening PAOD including gangrene or ischaemic rest pain; surgical or endovascular procedures during previous 3 months; gross obesity; hypertension; current malignancy; Buerger's disease or DVT in previous 3 months; inability to complete treadmill testing for reasons unrelated to intermittent claudication; bleeding problems
Interventions	Treatment: cilostazol 100 mg, twice daily, oral administration Control: placebo Duration: 6 weeks
Outcomes	ICD, ACD, subjective claudication improvement by patient, doppler‐measured limb pressures; measured at baseline and weeks 3 and 6
Notes	Immediate‐incline treadmill method: incline load started immediately at 10% and remained constant with speed constant at 3.2km/h. Only to be stopped for claudication of sufficient severity to cause the subject to be unable to continue 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	Low risk	Dropouts were similar between the two treatment groups, as shown in Table 31
Selective reporting (reporting bias)	High risk	Subjective claudication improvement or doppler‐measured limb pressures were not reported
Other bias	Unclear risk	Study supported by Otsuka America Pharmaceutical Inc