York Trials Unit, Department of Health Sciences, University of York, Heslington, York, YO10 5DD, UK.
Department of Health Sciences, University of York, Heslington, York, YO10 5DD, UK.
Trials. 2019 Jul 26;20(1):459. doi: 10.1186/s13063-019-3480-7.
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 or > 5 cm). 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.
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.
静脉性腿部溃疡 (VLU) 需要数月时间才能愈合，25%的溃疡无法愈合。静脉性腿部溃疡的主要治疗方法是压迫疗法，很少有其他治疗方法。两项先前的试验表明，低剂量阿司匹林可能会缩短愈合时间，但这些试验不够有力。
一项多中心、试点、二期、随机、双盲、平行组、安慰剂对照、疗效试验 (RCT) 进行，以确定：阿司匹林是否能改善 VLU 愈合时间；阿司匹林在该人群中的安全性；治疗依从性；以及三期试验的可行性。我们从二级护理机构招募年龄≥18 岁、患有慢性 VLU 且不规律服用阿司匹林的患者。参与者被随机分配（1:1）接受每天 300 毫克阿司匹林或安慰剂，外加标准护理，标准护理包括多成分压迫疗法，尽可能在脚踝处达到 40mmHg。随机分组按溃疡大小（≤5cm 或>5cm）分层。主要终点是溃疡愈合时间，定义为“在无需包扎（无结痂）且无需敷料的情况下完全上皮愈合”。所有接受至少一剂研究药物的参与者均评估安全性结果。
从 8 个地点招募了 27 名患者（目标为 100 名患者）。招募时间短，大量患者不符合入选标准是招募的主要障碍。在调整对数溃疡面积和持续时间后，参考溃疡的愈合时间没有差异（风险比 0.58，95%置信区间 0.18 至 1.85；p=0.357）。记录了一例与阿司匹林相关的预期严重不良事件。探索了一些改进招募的方案。
没有证据表明阿司匹林能加速慢性 VLU 的愈合。然而，由于招募的参与者人数较少，分析结果没有统计学意义。为了进行三期（有效性）试验，试验设计需要进行重大修改。
Clinicaltrials.gov，NCT02333123。于 2014 年 11 月 5 日注册。
