Search

Background: Venous Leg Ulcers can take many months to heal and 25% fail to heal. The main treatment for venous leg ulcers (VLUs) 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 300mg 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 cm2 or >5 cm2). 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: 27 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, related to aspirin, serious adverse event 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; 5/11/2014. URL https://clinicaltrials.gov/ct2/show/NCT02333123 (342 words. Limit 350) Keywords: Trial, pilot, randomised, aspirin, placebo, venous, ulcer, wound, double-blind, phase-II (up to 10 key words permitted)

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 cm2 or > 5 cm2). 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.

Background: \ud Cerebral small vessel disease is a common cause of vascular cognitive impairment in older people, with no licensed treatment. Cerebral blood flow is reduced in small vessel disease. Tadalafil is a widely prescribed phosphodiesterase-5 inhibitor that increases blood flow in other vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease.\ud \ud Methods/design: \ud Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo. Sample size: 54 participants are required to detect a 15% increase in cerebral blood flow in subcortical white matter (p

SPIRIT 2013 checklist: recommended items to address in a clinical trial protocol and related documents. (DOC 120Â kb)

Schematic of AVURT trial design. (PDF 88 kb)

Schematic of AVURT trial design. (PDF 88 kb)

Previous randomised trials investigating aspirin in the treatment of VLU. (DOCX 15 kb)

Summary flow chart of AVURT assessments. (PDF 173 kb)

Summary flow chart of AVURT assessments. (PDF 173 kb)