Aspirin versus placebo for the treatment of venous leg ulcers-a phase II, pilot, randomised trial (AVURT)

Tilbrook Helen, Cook Liz, Clark Laura, Sbizzera Illary, Bland Martin, Buckley Hannah, Chetter Ian, Dumville Jo, Fenner Chris, Forsythe Rachael, Gabe Rhian, Harding Keith, Layton Alison, Lindsay Ellie, Mc Daid Catriona, Moffatt Christine, Rolfe Debbie, Stansby Gerard, Torgerson David, Vowden Peter, Williams Laurie, Hinchliffe Robert, Tilbrook Helen, Cook Liz, Clark Laura, Sbizzera Illary, Bland Martin, Buckley Hannah, Chetter Ian, Dumville Jo, Fenner Chris, Forsythe Rachael, Gabe Rhian, Harding Keith, Layton Alison, Lindsay Ellie, Mc Daid Catriona, Moffatt Christine, Rolfe Debbie, Stansby Gerard, Torgerson David, Vowden Peter, Williams Laurie, Hinchliffe Robert

Abstract

Background: Venous leg ulcers (VLUs) can take many months to heal and 25% fail to heal. The main treatment for venous leg ulcers is compression therapy and few additional therapies exist. Two previous trials indicated that low-dose aspirin may improve healing time, but these trials were insufficiently robust.

Methods: A multi-centred, pilot, phase II, randomised, double blind, parallel-group, placebo-controlled, efficacy trial (RCT) was conducted to determine: if aspirin improves VLU healing time; the safety of aspirin in this population; treatment compliance; and the feasibility of recruitment to a phase III trial. We recruited patients from secondary care who were aged ≥ 18 years, had a chronic VLU and not regularly taking aspirin. Participants were randomly assigned (1:1) to receive 300 mg of daily aspirin or placebo in addition to standard care, which consisted of multi component compression therapy aiming to deliver 40 mmHg at the ankle where possible. The randomisation list was stratified by ulcer size (≤ 5 cm2 or > 5 cm2). The primary endpoint was time to ulcer healing, which was defined as 'complete epithelial healing in the absence of scab (eschar) with no dressing required'. Safety outcomes were assessed in all participants who received at least one dose of the study drug.

Results: Twenty-seven patients were recruited from eight sites (target 100 patients). A short time-frame to recruit and a large number of patients failing to meet the eligibility criteria were the main barriers to recruitment. There was no evidence of a difference in time to healing of the reference ulcer following adjustment for log ulcer area and duration (hazard ratio 0.58, 95% confidence interval 0.18 to 1.85; p = 0.357). One expected serious adverse event related to aspirin was recorded. A number of options to improve recruitment were explored.

Conclusions: There was no evidence that aspirin was effective in expediting the healing of chronic VLUs. However, the analysis was underpowered due to the low number of participants recruited. The trial design would require substantial amendment in order to progress to a phase III (effectiveness) trial.

Trial registration: Clinicaltrials.gov, NCT02333123. Registered on 5 November 2014.

Keywords: Aspirin; Double-blind; Phase II; Pilot; Placebo; Randomised; Trial; Ulcer; Venous; Wound.

Conflict of interest statement

C. Moffatt has received grant funding from three health science-based technology companies.

All others authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
AVURT pre-screening study flow
Fig. 2
Fig. 2
AVURT CONSORT diagram
Fig. 3
Fig. 3
Kaplan-Meier plot of time to ulcer healing by trial arm (unadjusted)

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Source: PubMed

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