Otsuka Study 21‐95‐201.

Methods	Study design: randomised, double‐blind, placebo‐controlled, clinical trial Intention to treat: yes; LOCF method Country: USA
Participants	Number randomised: 215 (cilostazol 150 mg n = 73; cilostazol 100 mg n = 72; placebo n = 70) Age (mean years): cilostazol 150 mg = 65; cilostazol 100 mg = 68; placebo = 66 Sex M/F: cilostazol 150 mg = 81%/19%; cilostazol 100 mg = 75%/25%; placebo = 81%/19% Inclusion criteria: > 40 years; atherosclerosis obliterans‐induced intermittent claudication for ≥ 6 months, stable for ≥ 3 months. Exclusion criteria: intermittent claudication associated with lower extremity ischaemic rest pain, ischaemic ulceration, gangrene or Buerger's disease; women of childbearing potential; sympathectomy or lower extremity arterial reparative surgery, including endovascular procedures in previous 3 months; greater than 60% above ideal body weight; current metastatic malignancy; DVT within previous 3 months; other exercise‐limiting disease; risk of or tendency to bleeding; pericarditis or pericardial effusions; platelet count < 130,000/cm3 or haematocrit < 30%; twice the normal values for AST or ALT; serum creatinine > 2.5 mg/dL; current alcohol or other drug abuse, or use of investigational drug within the past 30 days; requirement for uninterrupted use of pentoxifylline, NSAIDs, certain antiplatelet and anticoagulant medications
Interventions	Treatment 1: cilostazol 150 mg, twice daily Treatment 2 : cilostazol 100 mg, twice daily Control: placebo, twice daily Duration: 12 weeks
Outcomes	Trough ACD and ICD, subjective claudication improvement as per patient and physician, doppler‐measured limb pressures, quality of life questionnaires; measured at baseline then weeks 4, 8 and 12
Notes	Treadmill tests done by "immediate‐incline" method: incline load started immediately at 12.5% (and remained constant) with speed constant at 3.2km/h. Tests were only to be stopped for claudication Two‐week 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	Accounted for all dropouts
Selective reporting (reporting bias)	High risk	Report did not include ICD data at 4, 8 and 12 weeks, subjective claudication improvement or doppler limb pressures. Did not report quality of life results, but noted no significant differences between the groups
Other bias	Unclear risk	Study supported by Otsuka America Pharmaceutical Inc