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Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic, randomised, double blind, placebo controlled trial (Aspirin4VLU)

BMJ 2017; 359 doi: https://doi.org/10.1136/bmj.j5157 (Published 24 November 2017) Cite this as: BMJ 2017;359:j5157
  1. Andrew Jull, associate professor1 2,
  2. Angela Wadham, senior project manager2,
  3. Chris Bullen, professor2,
  4. Varsha Parag, senior biostatistician2,
  5. Ngaire Kerse, professor3,
  6. Jill Waters, geriatrician4
  1. 1School of Nursing, University of Auckland, Auckland, New Zealand
  2. 2National Institute for Health Innovation, University of Auckland, Auckland, New Zealand
  3. 3School of Population Health, University of Auckland, Auckland, New Zealand
  4. 4Adult Long Term Conditions and Community Services, Auckland District Health Board, Auckland, New Zealand
  1. Correspondence to: A Jull a.jull{at}auckland.ac.nz
  • Accepted 23 October 2017

Abstract

Objective To determine the effect of low dose aspirin on ulcer healing in patients with venous leg ulcers.

Design Pragmatic, community based, parallel group, double blind, randomised controlled trial.

Setting Five community nursing centres in New Zealand.

Participants 251 adults with venous leg ulcers who could safely be treated with aspirin or placebo: 125 were randomised to aspirin and 126 to placebo.

Interventions 150 mg oral aspirin daily or matching placebo for up to 24 weeks treatment, with compression therapy as standard background treatment.

Main outcome measures The primary outcome was time to complete healing of the reference ulcer (largest ulcer if more than one ulcer was present). Secondary outcomes included proportion of participants healed, change in ulcer area, change in health related quality of life, and adverse events. Analysis was by intention to treat.

Results The median number of days to healing of the reference ulcer was 77 in the aspirin group and 69 in the placebo group (hazard ratio 0.85, 95% confidence interval 0.64 to 1.13, P=0.25). The number of participants healed at the endpoint was 88 (70%) in the aspirin group and 101 (80%) in the placebo group (risk difference −9.8%, 95% confidence interval −20.4% to 0.9%, P=0.07). Estimated change in ulcer area was 4.1 cm2 in the aspirin group and 4.8 cm2 in the placebo group (mean difference −0.7 cm2, 95% confidence interval −1.9 to 0.5 cm2, P=0.25). 40 adverse events occurred among 29 participants in the aspirin group and 37 adverse events among 27 participants in the placebo group (incidence rate ratio 1.1, 95% confidence interval 0.7 to 1.7, P=0.71).

Conclusion Our findings do not support the use of low dose aspirin as adjuvant treatment for venous leg ulcers.

Trial registration ClinicalTrials.gov NCT02158806.

Footnotes

  • We thank the following for their support our clinical partners, the research nurses, the data safety monitoring board, the general staff of the National Institute for Health Innovation, and Auckland Uniservices; the following clinicians for their knowledge and continued support: Leisa Neumann, Trish Johns, Julie Betts (Maria Schollum), Catherine Hammond, and Emil Schmidt, site investigators (subsite investigators), respectively, at Auckland District Health Board, Counties Manukau Health, Waikato District Health Board, Nurse Maude Association, and Southern District Health Board; the Aspirin4VLU research nurses (Lee McGarvey, Joy Atwood, Desley Rosevear, Bronwen Meredith, and Sue Lee), the district nurses and the general practitioners for their generous support of this trial. We thank the members of the data safety monitoring board, Thomas Lumley (Department of Statistics, University of Auckland), Joanne Barnes (School of Pharmacy, University of Auckland) and Vanessa Selak (School of Population Health, University of Auckland). We thank the following National Institute for Health Innovation for their work operationalising the trial: Yannan Jiang (independent peer review of primary analysis), Michelle Jenkins, John Faatui, and Terry Holloway (data management), Colleen Ng, Clark Mills, Stuart Uren, and Stephen Boswell (information technology), and Kate Hudson and Sarah Douglas (administration). We thank Sheila Fisher (contracts) from Auckland Uniservices. Finally, we thank the participants and their families and whānau for contributing their experience and data for the benefit of others. This trial would not have been possible without their altruism.

  • Contributors: AJ conceived the study and is the guarantor. AJ, CB, VP, NK, and JW designed the trial and obtained funding. AJ (chair), AW, CB, VP, NK, and JW developed the trial protocol, developed or reviewed study materials (Investigator’s Brochure, Manual of Procedures, Case Record Forms, Pharmacovigilance and Safety Reporting Manual), and were members of the trial steering committee. CB reviewed all adverse events. VP drafted the statistical analysis plan, which was signed off by the trial steering committee. VP prepared blinded reports for the data safety monitoring board, conducted all the analyses, and prepared the statistical report. The trial steering committee reviewed the statistical report and agreed to an interpretation of the data when blind. AJ drafted the paper for review by the trial steering committee. All members had access to the statistical analysis, commented on the paper, and signed off on the final draft for submission.

  • Funding: The Health Research Council (HRC) of New Zealand was the sole funder of this trial (project grant 14/269). The HRC is a government funded statutory body responsible for managing the government’s investment in health research through competitive peer reviewed grants. The HRC had no role in the conduct or analysis of the Aspirin4VLU trial.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; the HRC of New Zealand funded this trial; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the Northern A Health and Disability Ethics Committee (14/NTA/136), and institutional approvals were obtained from each participating study centre.

  • Data sharing: Requests for deidentified individual participant data or study documents will be considered where the proposed use aligns with public good purposes, does not conflict with other requests, or planned use by the trial steering committee, and the requestor is willing to sign a data access agreement. Contact is though the corresponding author.

  • Transparency: The guarantor (AJ) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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