Aspirin versus placebo for the treatment of Venous Leg Ulcers – a phase II, pilot, Randomised Trial (AVURT)

TY - JOUR

T1 - Aspirin versus placebo for the treatment of Venous Leg Ulcers – a phase II, pilot, Randomised Trial (AVURT)

AU - Tilbrook, Helen Elizabeth

AU - Cook, Elizabeth

AU - Clark, Laura Kate

AU - Sbizerra, Illary

AU - Bland, John Martin

AU - Hannah, Buckley

AU - Chetter, Ian

AU - Dumville, Jo

AU - Fenner, Chris

AU - Forsythe, Rachael

AU - Gabe, Rhian

AU - Harding, Keith

AU - Lindsay, Ellie

AU - McDaid, Catriona Maria

AU - Moffatt, Christine

AU - Rolfe, Debbie

AU - Stansby, Gerard

AU - Torgerson, David John

AU - Vowden, Peter

AU - Williams, Laurie

AU - Hinchliffe, Robert

N1 - © The Author(s). 2019

PY - 2019/7/26

Y1 - 2019/7/26

N2 - Background: Venous Leg Ulcers can take many months to heal and 25% fail to heal. The main treatment for venous leg ulcers (VLUs) 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 300mg 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: 27 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, related to aspirin, serious adverse event 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; 5/11/2014. URL https://clinicaltrials.gov/ct2/show/NCT02333123 (342 words. Limit 350) Keywords: Trial, pilot, randomised, aspirin, placebo, venous, ulcer, wound, double-blind, phase-II (up to 10 key words permitted)

AB - Background: Venous Leg Ulcers can take many months to heal and 25% fail to heal. The main treatment for venous leg ulcers (VLUs) 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 300mg 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: 27 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, related to aspirin, serious adverse event 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; 5/11/2014. URL https://clinicaltrials.gov/ct2/show/NCT02333123 (342 words. Limit 350) Keywords: Trial, pilot, randomised, aspirin, placebo, venous, ulcer, wound, double-blind, phase-II (up to 10 key words permitted)

UR - https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-019-3480-7

U2 - 10.1186/s13063-019-3480-7

DO - 10.1186/s13063-019-3480-7

M3 - Article

SN - 1745-6215

VL - 80

JO - Trials

JF - Trials

M1 - 459 (2019)

ER -