Strandness 2002.

Methods	Study design: multicentre, randomised, double‐blind, placebo‐controlled, phase III trial Intention to treat: yes; LOCF method Country: USA
Participants	Number randomised: 394 (cilostazol 100 mg n = 133; cilostazol 50 mg n = 132; placebo n = 129) Age (mean years ± SE): cilostazol 100 mg = 63.1 ± 10.2; cilostazol 50 mg = 63.9 ± 8.7; placebo = 64.4 ± 10.2 Sex M/F: cilostazol 100 mg = 102/31; cilostazol 50 mg = 98/34; placebo = 100/29 Inclusion criteria: ≥ 40 years; at least 6 month history of stable symptomatic intermittent claudication secondary to PAD; and reproducible walking distances on screening treadmill (20% or less variation in MWD on two consecutive tests); termination of all screening treadmill tests solely for reasons of claudication pain; ability to walk between 30 and 200 m; resting ABI less than 0.90 and at least a 10 mmHg decrease in ankle systolic blood pressure in the reference leg at completion of test Exclusion criteria: ischaemic pain at rest; gross obesity; childbearing potential; hypertension; malignancy; exercise limiting cardiac disease; history of bleeding tendencies; concomitant use of antiplatelet, anticoagulant, haemorheologic or NSAIDs
Interventions	Treatment 1: cilostazol 100 mg, twice daily Treatment 2: cilostazol 50 mg, twice daily Control: placebo, twice daily Duration: 24 weeks
Outcomes	MWD, PFWD, doppler‐measured bilateral peripheral limb pressures, quality of life and functional status, end‐of‐treatment global therapeutic benefit (physician and participant), cardiovascular morbidity, all‐cause mortality; Outcomes measured at baseline, weeks 2 and 4, then every 4 weeks until 24 weeks
Notes	Treadmill test consisted of standardised 2 mph at 12.5% incline 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	Low risk	"Cilostazol was packaged as a 50mg tablet and a placebo dummy was given to maintain double blind conditions". "The blind was reportedly not broken during the course of the study"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"An independent committee, blinded to treatment assignment, adjudicated all patient death and any possible cardiovascular morbid events according to the predefined morbidity criteria". Although it was not directly addressed for other outcomes, it is assumed blinding was adequate
Incomplete outcome data (attrition bias) All outcomes	Low risk	"There were no clinically or statistically significant differences events, serious or adverse events, discontinuation of therapy due to adverse events and death"
Selective reporting (reporting bias)	High risk	ABI data was listed as a secondary outcome but not reported on, aside from a comment in the discussion for which no data was given to support it
Other bias	Unclear risk	Study supported by Otsuka America Pharmaceutical Inc

ABI: ankle brachial index
 ACD: absolute claudication distance
 ALT: alanine transaminase
 AST: aspartate aminotransferase
 bid: twice daily
 CLZ: cilostazol
 cm: centimetre
 COM: Claudication Outcome Measures
 CRP: C‐reactive protein
 DVT: deep vein thrombosis
 HDL: high‐density lipoprotein
 ICD: initial claudication distance
 km/h: kilometres per hour
 LDL: low‐density lipoprotein
 LOCF: last observation carried forward
 m: metres
 mg: milligrams
 MI: myocardial infarction
 mph: miles per hour
 MWD: maximum walking distance (equivalent to ACD)
 NSAIDs: non‐steroidal anti‐inflammatory agents
 PAD: peripheral arterial disease
 PAOD: peripheral arterial occlusive disease
 PAR: Physical Activity Recall
 PFWD: pain‐free walking distance (equivalent to ICD)
 SE: standard error
 SF‐36: Medical Outcomes Scale Short Form‐36
 WIQ: Walking Impairment Questionnaire