Accelerate CIC, Centenary Wing, St Joseph's Hospice, London, UK.
CRN Eastern, Norfolk Community Health and Care Trust, Norwich, UK.
Int Wound J. 2023 Aug;20(6):2260-2268. doi: 10.1111/iwj.14107. Epub 2023 Feb 13.
A major obstacle to the development of new treatments for venous leg ulcers is the difficulty in generating evidence for their effectiveness. Randomised controlled trials using complete healing as the endpoint are seldom powered to be successful, owing to the heterogeneity of cohorts. A novel approach to the evaluation of treatments is presented, using a self-controlled trial model and two metrics of short-term healing rate as alternate endpoints: rate of wound margin advance, and percentage area reduction over 4 weeks. Two different treatment regimens are compared: multi-layer compression alone, versus multi-layer compression combined with activation of the venous leg pump by neuromuscular stimulation. With 60 patients, adding neuromuscular stimulation to multilayer compression resulted in a significant two-fold increase in the rate of wound healing over a 4-week period, both in terms of wound margin advance and in terms of percentage area reduction. The use of these short-term intermediate endpoint metrics together with a self-controlled study design offers potential for distinguishing between the relative efficacies of interventions more rapidly, with greater sensitivity, and with fewer subjects than a conventional RCT cohort model.
静脉溃疡新疗法开发的主要障碍是难以为其疗效生成证据。由于队列的异质性，使用完全愈合作为终点的随机对照试验很少有成功的可能性。本文提出了一种评估治疗方法的新方法，使用自我对照试验模型和两种短期愈合率指标作为替代终点：伤口边缘进展率和 4 周内的面积减少百分比。比较了两种不同的治疗方案：单纯多层压缩与多层压缩联合神经肌肉刺激激活静脉足泵。在 60 名患者中，与多层压缩相比，添加神经肌肉刺激可使 4 周内的伤口愈合率显著提高两倍，无论是伤口边缘进展还是面积减少百分比。使用这些短期中间终点指标以及自我对照研究设计，与传统 RCT 队列模型相比，具有更快、更敏感、更少的受试者来区分干预措施相对疗效的潜力。
