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

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 cm 2 or > 5 cm 2 ). 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.

Medikamentöse Therapien des Ulcus cruris

“…In nachfolgenden größeren Studien mit bis zu 251 Patienten konnte der Vorteil jedoch nicht bestätigt werden. Im Gegenteil zeigte sich eher eine schlechtere Abheilung unter der Einnahme von ASS [6][7][8].…”

Bacteriophages for Chronic Wound Treatment: From Traditional to Novel Delivery Systems

“…Also, adding systemic granulocyte-colony stimulating factors, which help in the release and function improvement of neutrophil endothelial progenitor cells (usually lacking in diabetic patients), or hyperbaric oxygen, which improves the oxygen supply to wounds, showed a reduction in the need for more extended hospitalization stays and the need for amputations in people with chronic wounds [92,93]. Many other systemic drugs (e.g., aspirin, flavonoids, thromboxane alpha-2 agonists, sulodexide) improve the wound environment [94][95][96][97]. However, caution in the use of this latter treatment is needed to evaluate if the benefits overcome their associated risks: antimicrobial resistance, allergic reactions, drug toxicities (cardiac, hepatic, renal, and hematopoietic), and drug interactions [98].…”