{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T08:54:20Z","timestamp":1770454460859,"version":"3.49.0"},"reference-count":44,"publisher":"National Institute for Health and Care Research","issue":"55","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["13\/87\/08"],"award-info":[{"award-number":["13\/87\/08"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\">\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-2\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Primary objective \u2013 to assess the effects of 300\u2009mg of aspirin (daily) versus placebo on the time to healing of the reference VLU. Secondary objectives \u2013 to assess the feasibility of leading into a larger pragmatic Phase III trial and the safety of aspirin in this population.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-3\">\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>A multicentred, pilot, Phase II randomised double-blind, parallel-group, placebo-controlled efficacy trial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-4\">\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Community leg ulcer clinics or services, hospital outpatient clinics, leg ulcer clinics, tissue viability clinics and wound clinics in England, Wales and Scotland.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-5\">\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Patients aged \u2265\u200918 years with a chronic VLU (i.e. the VLU is &gt;\u20096 weeks in duration or the patient has a history of VLU) and who are not regularly taking aspirin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-6\">\n                  <jats:title>Interventions<\/jats:title>\n                  <jats:p>300\u2009mg 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\u2009mmHg at the ankle when possible.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-7\">\n                  <jats:title>Randomisation<\/jats:title>\n                  <jats:p>Participants were allocated in a 1\u2009:\u20091 (aspirin\u2009:\u2009placebo) ratio by the Research Pharmacy, St George\u2019s 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 (\u2264\u20095cm<jats:sup>2<\/jats:sup> or &gt;\u20095cm<jats:sup>2<\/jats:sup>).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-8\">\n                  <jats:title>Main outcome measure<\/jats:title>\n                  <jats:p>The primary outcome was time to healing of the largest eligible ulcer (reference ulcer).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-9\">\n                  <jats:title>Feasibility results \u2013 recruitment<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-10\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The average age of the 27 randomised participants (placebo, <jats:italic>n<\/jats:italic>\u2009=\u200913; aspirin, <jats:italic>n<\/jats:italic>\u2009=\u200914) was 62 years (standard deviation 13 years), and two-thirds were male (<jats:italic>n<\/jats:italic>\u2009=\u200918). Participants had their reference ulcer for a median of 15 months, and the median size of ulcer was 17.1\u2009cm<jats:sup>2<\/jats:sup>. 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; <jats:italic>p<\/jats:italic>\u2009=\u20090.357). One expected, related serious adverse event was recorded for a participant in the aspirin group.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-11\">\n                  <jats:title>Limitations<\/jats:title>\n                  <jats:p>The trial under-recruited because many patients did not meet the eligibility criteria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-12\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-13\">\n                  <jats:title>Trial registration<\/jats:title>\n                  <jats:p>Clinical Trials.gov NCT02333123; European Clinical Trials Database (EudraCT) 2014-003979-39.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-14\">\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in <jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 22, No. 55. See the NIHR Journals Library website for further project information.<\/jats:p>\n               <\/jats:sec>","DOI":"10.3310\/hta22550","type":"journal-article","created":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T12:58:52Z","timestamp":1539694732000},"page":"1-138","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["AVURT: aspirin versus placebo for the treatment of venous leg ulcers \u2013 a Phase II pilot randomised controlled trial"],"prefix":"10.3310","volume":"22","clinical-trial-number":[{"clinical-trial-number":"nct02333123","registry":"10.18810\/clinical-trials-gov","type":"results"},{"clinical-trial-number":"2014-003979-39","registry":"10.18810\/euctr","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1312-5780","authenticated-orcid":true,"given":"Helen","family":"Tilbrook","sequence":"first","affiliation":[{"name":"York Trials Unit, Department of Health Sciences, University of 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