Selvarajah Dinesh, Petrie Jennifer, White David, Julious Steven, Bortolami Oscar, Cooper Cindy, Bradburn Mike, Loban Amanda, Bowler Helen, Swaby Lizzie, Sutherland Katie, Tesfaye Solomon
Department of Oncology and Human Metabolism, Medical School, University of Sheffield, Sheffield, UK.
Clinical Trials Research Unit, University of Sheffield, Sheffield, UK.
Trials. 2018 Oct 22;19(1):578. doi: 10.1186/s13063-018-2959-y.
The number of people with diabetes is growing rapidly. Diabetes can cause nerve damage leading to severe pain in the feet, legs and hands, which is known as diabetic peripheral neuropathic pain (DPNP). In the UK, the National Institute for Health and Care Excellence (NICE) recommends amitriptyline, duloxetine, pregabalin or gabapentin as initial treatment for DPNP. If this is not effective, adding one of the other drugs in combination with the first is recommended. NICE points out that these recommendations are not based on robust evidence. The OPTION-DM randomised controlled trial has been designed to address this evidence deficit, with the aims of determining the most clinically beneficial, cost-effective and tolerated treatment pathway for patients with DPNP.
METHODS/DESIGN: A multicentre, double-blind, centre-stratified, multi-period crossover study with equal allocation to sequences (1:1:1:1:1:1) of treatment pathways. Three hundred and ninety-two participants will be recruited from secondary care DPNP centres in the UK. There are three treatment pathways: amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline and duloxetine supplemented with pregabalin. All participants will receive all three pathways and randomisation will determine the order in which they are received. The primary outcome is the difference between 7-day average 24-h pain scores on an 11-point NRS scale measured during the final follow-up week of the treatment pathway. Secondary outcomes for efficacy, cost-effectiveness, safety, patient-perceived tolerability and subgroup analysis will be measured at week 6 and week 16 of each pathway.
The study includes direct comparisons of the mainstay treatment for DPNP. This novel study is designed to examine treatment pathways and capture clinically relevant outcomes which will make the results generalisable to current clinical practice. The study will also provide information on health economic outcomes and will include a subgroup study to provide information on whether patient phenotypes predict response to treatment.
ISRCTN17545443 . Registered on 12 September 2016.
糖尿病患者人数正在迅速增长。糖尿病可导致神经损伤，进而引起足部、腿部和手部的剧痛，这被称为糖尿病性周围神经病理性疼痛（DPNP）。在英国，国家卫生与临床优化研究所（NICE）推荐阿米替林、度洛西汀、普瑞巴林或加巴喷丁作为DPNP的初始治疗药物。如果这种治疗无效，则建议加用其他药物之一与第一种药物联合使用。NICE指出，这些建议并非基于确凿的证据。OPTION-DM随机对照试验旨在解决这一证据不足的问题，其目的是为DPNP患者确定最具临床益处、成本效益且耐受性良好的治疗方案。
方法/设计：一项多中心、双盲、中心分层、多阶段交叉研究，对治疗方案序列（1:1:1:1:1:1）进行均等分配。将从英国二级护理DPNP中心招募392名参与者。有三种治疗方案：阿米替林加用普瑞巴林、普瑞巴林加用阿米替林以及度洛西汀加用普瑞巴林。所有参与者都将接受这三种方案，随机分组将决定他们接受方案的顺序。主要结局是在治疗方案的最后随访周期间，采用11点数字评定量表（NRS）测量的7天平均24小时疼痛评分之间的差异。每种方案的第6周和第16周将测量疗效、成本效益、安全性、患者感知的耐受性和亚组分析等次要结局。
该研究包括对DPNP主要治疗方法的直接比较。这项新颖的研究旨在检验治疗方案并获取临床相关结局，这将使研究结果能够推广至当前临床实践。该研究还将提供有关健康经济结局的信息，并将包括一项亚组研究，以提供关于患者表型是否可预测治疗反应的信息。
ISRCTN17545443。于2016年9月12日注册。
