| Study characteristics |
| 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 stated 780 as the number of participants, 260 in each group, but the study characteristics on pg 177 of the report had 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: 40 years or older, with PAD and IC 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, QoL (SF‐36, WIQ, COM), adverse events, vascular events; measured at baseline and then 4 weeks until 24 weeks |
| Funding |
Otsuka America Pharmaceutical Inc. |
| Declaration of interests |
Not reported ‐ source of the study data was a pharmaceutical submission to National Institute for Care and Excellence. |
| Notes |
Constant workload treadmill test: 3.2 km/h at a constant 12.5% grade
Study was 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 was insufficient description to determine if blinding was adequate. |
| Blinding of outcome assessment (detection bias)
All outcomes |
Unclear risk |
Blinding of assessors was 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 |
Low risk |
No evidence of other bias |
