OPAL 研究：一项随机、安慰剂对照的阿片类镇痛药试验，旨在减轻急性脊柱疼痛患者的疼痛严重程度——统计分析计划。

OPAL: a randomised, placebo-controlled trial of opioid analgesia for the reduction of pain severity in people with acute spinal pain-a statistical analysis plan.

机构信息

Institute for Musculoskeletal Health, Sydney Local Health District and The University of Sydney, Level 10N, KGV Building, Missenden Road, Camperdown, Sydney, New South Wales, Australia.

Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital Sydney and St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.

出版信息

Trials. 2022 Mar 14;23(1):212. doi: 10.1186/s13063-022-06028-y.

DOI:10.1186/s13063-022-06028-y

PMID:35287698

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8919636/

Abstract

BACKGROUND

Low back and neck pain are a leading cause of disease burden globally. Opioids are recommended in guidelines for acute low back and neck pain; however, there is a lack of compelling efficacy data to support this.

METHODS

The OPAL trial is a prospectively registered, triple-blinded, randomised, placebo-controlled trial. Patients with acute (≤12 weeks duration) back and/or neck pain receive guideline care plus either an opioid (oxycodone + naloxone, up to 20 mg per day) or a placebo for up to 6 weeks or earlier, if pain is resolved. The primary outcome is pain measured using the Pain Severity Score of the Brief Pain Inventory with the primary time point being 6 weeks. Secondary outcomes include physical function, time to recovery, quality of life, adverse events and risk of opioid misuse. Outcomes are collected at weeks 2, 4, 6, 12, 26 and 52. Analysis will be done on an intention-to-treat principle. p values of < 0.05 will be considered significant and 95% confidence intervals will be reported. Repeated-measures linear mixed models will be used to assess the effect of the treatment group on the primary outcome and continuous secondary outcomes. Adverse events will be compared between groups using Fisher's exact test. Cost-effectiveness analyses will be conducted if a treatment effect on pain is seen at week 6. Subgroup analyses will be performed to assess whether pain duration and pain location are treatment effect modifiers.

DISCUSSION

The OPAL trial will provide important evidence about whether a short course of opioids is effective in the treatment of acute non-specific low back and/or neck pain. This pre-specified statistical analysis plan details the methodology for the analysis of the OPAL trial results.

TRIAL REGISTRATION

ACTRN12615000775516 . The trial has completed recruitment. Follow-up on the last patient will be completed in March 2022.

摘要

背景

下背痛和颈痛是全球疾病负担的主要原因。指南推荐在急性下背痛和颈痛中使用阿片类药物；然而，缺乏令人信服的疗效数据来支持这一点。

方法

OPAL 试验是一项前瞻性注册、三盲、随机、安慰剂对照试验。患有急性（≤12 周）下背痛和/或颈痛的患者接受指南护理，外加阿片类药物（羟考酮+纳洛酮，每天最多 20 毫克）或安慰剂，持续 6 周或更早，如果疼痛缓解。主要结局是使用简明疼痛量表的疼痛严重程度评分测量，主要时间点为 6 周。次要结局包括身体功能、恢复时间、生活质量、不良事件和阿片类药物滥用风险。结果在第 2、4、6、12、26 和 52 周收集。分析将按照意向治疗原则进行。p 值<0.05 将被认为具有统计学意义，并将报告 95%置信区间。重复测量线性混合模型将用于评估治疗组对主要结局和连续次要结局的影响。将使用 Fisher 精确检验比较组间不良事件。如果在第 6 周观察到疼痛的治疗效果，将进行成本效益分析。将进行亚组分析，以评估疼痛持续时间和疼痛位置是否为治疗效果的调节剂。