Otsuka Study 21‐98‐213.

Methods	Study design: multicentre, randomised, double‐blind, placebo‐controlled, clinical trial Intention to treat: yes Country: USA
Participants	Number randomised: 785 (cilostazol n = 261; pentoxifylline n = 262; placebo n = 262) (several of the tables in the NICE report state 780 as the number of participants, 260 in each group, but the study characteristics on pg 177 of the report has n = 785 as the total number randomised) Age (mean years ± SE): cilostazol = 66.7 ± 9.9; pentoxifylline = 67.4 ± 9.4; placebo = not given Sex %M: cilostazol = 75.4; pentoxifylline = 76.9; placebo = 75.4 Inclusion criteria: $0 [sic] years or older, with PAD and intermittent claudication with stable symptoms for the preceding 3 months; PAD diagnosed as an abnormal resting ABI ≥ 0.4 and ≤ 0.9 in the reference leg with decline in post‐exercise ABI ≥ 10 mmHg as confirmation; symptomatic patients with normal resting ABI but with pressure drop of > 20 mmHg were also eligible; MWD varied by no more than 20% on two to three consecutive treadmill tests Exclusion criteria: limb‐threatening ischaemia; limb revascularisation within 3 months; unstable coronary artery disease; coronary revascularisation within 6 months; thromboangiitis obliterans; DVT within 3 months; symptomatic arrhythmia; conditions other than PAD that might limit exercise ability or preclude completion of the study; congestive heart failure
Interventions	Treatment 1: cilostazol 100 mg, twice daily Treatment 2: pentoxifylline 400 mg, three times daily Control: placebo Duration: 24 weeks
Outcomes	MWD, PFWD, all‐cause mortality, quality of life (SF‐36, WIQ, COM), adverse events, vascular events; measured at baseline an then 4 weeks until 24 weeks
Notes	Constant workload treadmill test: 3.2 km/h at a constant 12.5% grade Study is also known under the trial name PACE
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	No study report was available outside of the data collected from the NICE review
Selective reporting (reporting bias)	Unclear risk	No study protocol or report was available outside of the data collected from the NICE review
Other bias	Unclear risk	Study supported by Otsuka America Pharmaceutical Inc