Dawson DL, De Maioribus CA, Hagino RT, et al. The effect of withdrawal of drugs treating intermittent claudication. American Journal of Surgery 1999;178:141-46
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/10487267
| Methods | Study design: Single-blind placebo-controlled continuation study from a randomized double-blind trial with a parallel-design
Number of groups: Three groups |
| Participants | Number of participants: 60 randomized, 45 completed drug treatment
· Cilostazol deprescribing group: 16 randomized · Pentoxifyline deprescribing group: 13 randomized · Placebo: 16 randomized Age: · Cilostazol deprescribing group: 60.9 ± 7.5 years · Pentoxiflyinedeprescribing group: 67.9 ± 10.3 years · Placebo: 66.4 ± 7.3 years Sex: 6 female, 39 male Participants with dementia: No Inclusion criteria: · 40 years of age or older · Peripheral artery disease · Chronic stable claudication symptoms · Claudication symptoms must have been present for at least 6 months and unchanged during the previous 3 months Exclusion criteria: · Uncontrolled hypertension · Malignancy · Limb threatening ischemia · Recent lower extremity arterial revascularization (either surgical or endovascular) · Sympathectomy (within the prior 3 months) · Recent deep vein thrombosis (within the past 3 months) · Severe systemic illness · Any condition that interfered with their ability to perform a valid treadmill test (e.g., angina, dyspnea, orthopedic condition) Country: United States of America Setting: Community |
| Interventions | Medicine:
· Cilostazol 100mg twice-daily · Pentoxifylline 400mg three times daily Withdrawal Schedule: Not described |
| Outcomes | Maximal walking distance
Pain-free walking distance Resting Doppler limb pressures Safety and tolerability of the study medications were assessed for all subjects with clinical laboratory monitoring, electrocardiography, physical examination, vital signs, and adverse event reporting |
| Dates | Dates: Not described
Follow-up duration: 30 weeks |
| Funding sources | Otsuka America Pharmaceuticals, Inc., the US subsidiary of the manufacturer of cilostazol |
| Notes | Investigators remained blinded for the current deprescribing studythough participants were un-blinded at the end of the main study.
Additional information sought, but not received. |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | Unclear risk | Randomization method not described. |
| Allocation concealment (selection bias) | Unclear risk | Not described. |
| Blinding of participants and personnel (performance bias) | Low risk | Medication was over-encapsulated making the drugs look identical. This would have blinded participants. Would lack of blinding have made any difference to the outcome? I suspect it would not because the primary end-point was self determined by the patient who was blinded, and the secondary end-points were firstly patient determined pain-free walking distance and secondly objective (Doppler pressures). |
| Blinding of outcome assessment (detection bias) | Low risk | It is unclear whether the personnel and assessors would have been adequately blinded as littledescription is given. The only statement was “The investigators knew placebo was administeredduring the final 6 weeks of the study, but they remained blinded to the therapy of the initial 24 weeks.” |
| Incomplete outcome data (attrition bias) | High risk | 15 patients withdrew, but insufficient data were given to be able to assess reasons. It is likely that at least some of these could have been due to reasons related to the intervention. |
| Selective reporting (reporting bias) | Low risk | Maximum walking distance and pain-free walking distance were described fully. Resting Doppler limb pressures was not reported in the results. The authors included this in secondary end-points but as far as I can see, it was only used in initial screening as one method to define significant peripheral artery disease. The article specifies Doppler limb pressures as an end-point when the protocol does not mention the use of Dopplers as an end-point nor are results collected. |
| Other bias | High risk | This work was supported by Otsuka America Pharmaceuticals, Inc., the US subsidiary of the manufacturer of cilostazol. It appears that this subset was chosen for convenience i.e. they were all at one site. |