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


Journal

Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253

Informations de publication

Date de publication:
26 Jul 2019
Historique:
received: 19 12 2017
accepted: 29 05 2019
entrez: 28 7 2019
pubmed: 28 7 2019
medline: 6 2 2020
Statut: epublish

Résumé

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. 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 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. 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. Clinicaltrials.gov, NCT02333123. Registered on 5 November 2014.

Sections du résumé

BACKGROUND 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 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
RESULTS 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 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 BACKGROUND
Clinicaltrials.gov, NCT02333123. Registered on 5 November 2014.

Identifiants

pubmed: 31349862
doi: 10.1186/s13063-019-3480-7
pii: 10.1186/s13063-019-3480-7
pmc: PMC6660698
doi:

Substances chimiques

Cardiovascular Agents 0
Aspirin R16CO5Y76E

Banques de données

ClinicalTrials.gov
['NCT02333123']

Types de publication

Clinical Trial, Phase II Journal Article Multicenter Study Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

459

Subventions

Organisme : Department of Health
ID : 13/87/08
Pays : United Kingdom
Organisme : Health Technology Assessment Programme
ID : 13/87/08

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Auteurs

Tilbrook Helen (T)

York Trials Unit, Department of Health Sciences, University of York, Heslington, York, YO10 5DD, UK.

Cook Liz (C)

York Trials Unit, Department of Health Sciences, University of York, Heslington, York, YO10 5DD, UK.

Clark Laura (C)

York Trials Unit, Department of Health Sciences, University of York, Heslington, York, YO10 5DD, UK.

Sbizzera Illary (S)

York Trials Unit, Department of Health Sciences, University of York, Heslington, York, YO10 5DD, UK.

Bland Martin (B)

Department of Health Sciences, University of York, Heslington, York, YO10 5DD, UK.

Buckley Hannah (B)

Cancer Division, Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, LS2 9JT, UK.

Chetter Ian (C)

Academic Vascular Surgical Unit, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ, UK.

Dumville Jo (D)

Division of Nursing, Midwifery and Social Work, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Oxford Road, Manchester, M13 9PL, UK.

Fenner Chris (F)

Orthopaedic Department, West Middlesex Hospital, Twickenham Road, Isleworth, Middlesex, TW9 1UR, UK.

Forsythe Rachael (F)

Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.

Gabe Rhian (G)

Hull York Medical School & York Trials Unit, Department of Health Sciences, University of York, Heslington, York, YO10 5DD, UK.

Harding Keith (H)

Wound Healing, Cardiff University, School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.

Layton Alison (L)

Harrogate and District NHS Foundation Trust, Lancaster Park Road, Harrogate, HG2 7SX, UK.

Lindsay Ellie (L)

(Lay representative). The Lindsay Leg Club Foundation, PO Box 689, Ipswich, IP1 9BN, UK.

Mc Daid Catriona (MD)

York Trials Unit, Department of Health Sciences, University of York, Heslington, York, YO10 5DD, UK.

Moffatt Christine (M)

The University of Nottingham, School of Health Sciences, Derby Education Centre, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT, UK.

Rolfe Debbie (R)

Joint Research and Enterprise Office, St Georges University of London, Cranmer Terrace, London, SW17 0RE, UK.

Stansby Gerard (S)

Freeman Hospital, Freeman Road, Newcastle upon Tyne, NE7 7DN, UK.

Torgerson David (T)

York Trials Unit, Department of Health Sciences, University of York, Heslington, York, YO10 5DD, UK.

Vowden Peter (V)

Bradford Teaching Hospitals NHS Foundation Trust, Bradford Royal Infirmary, Duckworth Lane, Bradford, West Yorkshire, BD9 6RJ, UK.

Williams Laurie (W)

(Lay representative). The Lindsay Leg Club Foundation, PO Box 689, Ipswich, IP1 9BN, UK.

Hinchliffe Robert (H)

Bristol Centre for Surgical Research, Bristol NIHR Biomedical Research Centre, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK. robert.hinchliffe@bristol.ac.uk.

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Classifications MeSH