Data_Sheet_1_Open-Label Placebo Treatment for Acute Postoperative Pain (OLP-POP Study): Study Protocol of a Randomized Controlled Trial.docx

Introduction: Open-label placebos have been proposed as way of using long recognized analgesic placebo effects in an ethical manner. Recent evidence shows efficacy of open-label placebos for clinical conditions, but there is need for more research on open-label placebos in acute pain. In the treatment of acute postoperative pain, minimization of opioid related side effects remains one of the key challenges. Therefore, this study aims at investigating the potential of adding unconditioned open-label placebos to treatment as usual as a means of reducing opioid consumption and its related side effects in patients with acute postoperative pain.Methods and Analysis: This is the protocol of an ongoing single site randomized controlled trial. The first patient was enrolled in May 2020. In total, 70 patients suffering from acute postoperative pain following dorsal lumbar interbody fusion are randomized to either a treatment as usual group or an experimental intervention group. The treatment as usual group consists of participants receiving a patient-controlled morphine pump. On day 1 and 2 post-surgery, patients in the intervention group receive, in addition to treatment as usual, two open-label placebo injections per day along with an evidence-based treatment rationale explaining the mechanisms of placebos. The primary outcome is measured by means of self-administered morphine during day 1 and 2 post-surgery. Several other outcome measures including pain intensity and adverse events as well as potential predictors of placebo response are assessed. Analysis of covariance will be used to answer the primary research question and additional statistical techniques such as generalized linear mixed models will be applied to model the temporal course of morphine consumption.Discussion: This study will provide valuable insights into the efficacy of open-label placebos in acute pain and will potentially constitute an important step toward the implementation of open-label placebos in the clinical management of acute postoperative pain. In addition, it will shed light on a cost-efficient and patient-centered strategy to reduce opioid consumption and its related side effects, without any loss in pain management efficacy.Ethics and Dissemination: The “Ethikkommission Nordwest- und Zentralschweiz” (BASEC2020-00099) approved the study protocol. Results of the analysis will be submitted for publication in a peer-reviewed journal.Clinical Trial Registration: The study is registered at ClinicalTrials.gov (NCT04339023) and is listed in the Swiss national registry at kofam.ch (SNCTP000003720).

引言：开放标签安慰剂作为一种将长期以来公认的镇痛安慰剂效应以伦理方式应用于实践的方法，已被提出。近期研究表明，开放标签安慰剂在临床疾病治疗中具有疗效，但针对开放标签安慰剂在急性疼痛治疗中的研究仍需进一步深入。在急性术后疼痛治疗过程中，最小化阿片类药物相关副作用一直是一项关键挑战。因此，本研究旨在探讨将无条件开放标签安慰剂添加至常规治疗方案中，以降低急性术后疼痛患者阿片类药物使用量及其相关副作用的潜力。方法与分析：本项研究为一项正在进行的单中心随机对照试验的方案。首位患者于2020年5月被纳入研究。总共70名患有急性术后疼痛的腰椎间融合术患者被随机分配至常规治疗组或实验干预组。常规治疗组患者接受患者自控吗啡泵治疗。在术后第1天和第2天，干预组患者在常规治疗的基础上，每日接受两次开放标签安慰剂注射，并伴随基于证据的治疗原理，解释安慰剂的机制。主要结局指标通过术后第1天和第2天患者自我注射的吗啡量进行测量。此外，还评估了包括疼痛强度、不良事件以及安慰剂反应的潜在预测因素在内的其他结局指标。协方差分析将用于回答主要研究问题，并将应用广义线性混合模型等额外统计技术来模拟吗啡使用的时序进程。讨论：本研究将为开放标签安慰剂在急性疼痛治疗中的疗效提供宝贵见解，并可能成为在临床管理急性术后疼痛中实施开放标签安慰剂的重要一步。此外，它将揭示一种成本效益高且以患者为中心的策略，以降低阿片类药物使用及其相关副作用，而不会影响疼痛管理效果。伦理与传播：瑞士“Ethikkommission Nordwest- und Zentralschweiz”（BASEC2020-00099）批准了研究方案。分析结果将被提交至同行评审期刊发表。临床试验注册：该研究已在ClinicalTrials.gov（NCT04339023）注册，并在瑞士国家注册处kofam.ch（SNCTP000003720）列名。