Abstract
Background
Venous leg ulcers (VLUs) are the most common cause of leg ulceration, affecting 1 in 100 adults. VLUs may take many months to heal (25% fail to heal). Estimated prevalence is between 1% and 3% of the elderly population. Compression is the mainstay of treatment and few additional therapies exist to improve healing. Two previous trials have indicated that low-dose aspirin, as an adjunct to standard care, may improve healing time, but these trials were insufficiently robust. Aspirin is an inexpensive, widely used medication but its safety and efficacy in the treatment of VLUs remains to be established.
Objectives
Primary objective – to assess the effects of 300 mg of aspirin (daily) versus placebo on the time to healing of the reference VLU. Secondary objectives – to assess the feasibility of leading into a larger pragmatic Phase III trial and the safety of aspirin in this population.
Design
A multicentred, pilot, Phase II randomised double-blind, parallel-group, placebo-controlled efficacy trial.
Setting
Community leg ulcer clinics or services, hospital outpatient clinics, leg ulcer clinics, tissue viability clinics and wound clinics in England, Wales and Scotland.
Participants
Patients aged ≥ 18 years with a chronic VLU (i.e. the VLU is > 6 weeks in duration or the patient has a history of VLU) and who are not regularly taking aspirin.
Interventions
300 mg of daily oral aspirin versus placebo. All patients were offered care in accordance with Scottish Intercollegiate Guidelines Network (SIGN) guidance with multicomponent compression therapy aiming to deliver 40 mmHg at the ankle when possible.
Randomisation
Participants were allocated in a 1 : 1 (aspirin : placebo) ratio by the Research Pharmacy, St George’s University Hospitals NHS Foundation Trust, using a randomisation schedule generated in advance by the investigational medicinal product manufacturer. Randomisation was stratified according to ulcer size (≤ 5cm2 or > 5cm2).
Main outcome measure
The primary outcome was time to healing of the largest eligible ulcer (reference ulcer).
Feasibility results – recruitment
27 patients were recruited from eight sites over a period of 8 months. The target of 100 patients was not achieved and two sites did not recruit. Barriers to recruitment included a short recruitment window and a large proportion of participants failing to meet the eligibility criteria.
Results
The average age of the 27 randomised participants (placebo, n = 13; aspirin, n = 14) was 62 years (standard deviation 13 years), and two-thirds were male (n = 18). Participants had their reference ulcer for a median of 15 months, and the median size of ulcer was 17.1 cm2. There was no evidence of a difference in time to healing of the reference ulcer between groups in an adjusted analysis for log-ulcer area and duration (hazard ratio 0.58, 95% confidence interval 0.18 to 1.85; p = 0.357). One expected, related serious adverse event was recorded for a participant in the aspirin group.
Limitations
The trial under-recruited because many patients did not meet the eligibility criteria.
Conclusions
There was no evidence that aspirin was efficacious in hastening the healing of chronic VLUs. It can be concluded that a larger Phase III (effectiveness) trial would not be feasible.
Trial registration
Clinical Trials.gov NCT02333123; European Clinical Trials Database (EudraCT) 2014-003979-39.
Funding
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 55. See the NIHR Journals Library website for further project information.
Original language | English |
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Pages (from-to) | 1-138 |
Number of pages | 138 |
Journal | Health technology assessment |
Volume | 22 |
Issue number | 55 |
DOIs | |
Publication status | Published - 16 Oct 2018 |
Bibliographical note
© Queen’s Printer and Controller of HMSO 2018. This work was produced by Tilbrook et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for detailsKeywords
- Aged
- Aspirin/administration & dosage
- Chronic Disease
- Compression Bandages
- Double-Blind Method
- Female
- Humans
- Male
- Middle Aged
- Patient Compliance
- Pilot Projects
- United Kingdom
- Varicose Ulcer/drug therapy
- Wound Healing/drug effects