特立帕肽治疗阻塞性睡眠呼吸暂停：SURMOUNT-OSA 三期临床试验的原理、设计和样本基线特征。
Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial.
机构信息
University of California San Diego, La Jolla, CA, USA.
Eli Lilly and Company, Indianapolis, IN, USA.
出版信息
Contemp Clin Trials. 2024 Jun;141:107516. doi: 10.1016/j.cct.2024.107516. Epub 2024 Mar 26.
BACKGROUND
Weight reduction is a standard recommendation for obstructive sleep apnea (OSA) treatment in people with obesity or overweight; however, weight loss can be challenging to achieve and maintain without bariatric surgery. Currently, no approved anti-obesity medication has demonstrated effectiveness in OSA management. This study is evaluating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA in people with obesity.
METHODS
SURMOUNT-OSA, a randomized, placebo -controlled, 52-week phase 3 trial, is investigating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA (apnea hypopnea- index ≥15 events/h) in participants with obesity (body mass index ≥30 kg/m) and an established OSA diagnosis. SURMOUNT-OSA is made of 2 intervention-specific appendices (ISAs): ISA-1 includes participants with no current OSA treatment, and ISA-2 includes participants using positive airway pressure therapy. Overall, 469 participants have been randomized 1:1 to receive tirzepatide or placebo across the master protocol (ISA-1, n = 234; ISA-2, n = 235). All participants are also receiving lifestyle intervention for weight reduction.
RESULTS
The primary endpoint for the individual ISAs is the difference in apnea hypopnea- index response, as measured by polysomnography, between tirzepatide and placebo arms at week 52. Secondary endpoints include sleep apnea-specific hypoxic burden, functional outcomes, and cardiometabolic biomarkers. The trial employs digital wearables, including home sleep testing to capture time to improvement and accelerometry for daily physical activity assessment, to evaluate exploratory outcomes.
CONCLUSION
SURMOUNT-OSA brings a novel design to investigate if tirzepatide provides clinically meaningful improvement in obesity-related OSA by targeting the underlying etiology.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT05412004.
背景
减肥是肥胖或超重人群中阻塞性睡眠呼吸暂停（OSA）治疗的标准建议；然而，在没有减重手术的情况下，减肥可能具有挑战性。目前，尚无经过批准的减肥药在 OSA 管理中显示出有效性。本研究评估替西帕肽治疗肥胖人群中中重度 OSA 的疗效和安全性。
方法
SURMOUNT-OSA 是一项随机、安慰剂对照、52 周 3 期试验，正在评估替西帕肽治疗肥胖（体重指数≥30 kg/m）和已确诊 OSA 的参与者中中重度 OSA（呼吸暂停低通气指数≥15 次/小时）的疗效和安全性。SURMOUNT-OSA 由 2 个干预特定附录（ISA）组成：ISA-1 包括无当前 OSA 治疗的参与者，ISA-2 包括使用正压通气治疗的参与者。总体而言，469 名参与者按照 1:1 的比例随机分配接受替西帕肽或安慰剂（主方案，ISA-1，n=234；ISA-2，n=235）。所有参与者还接受生活方式干预以减轻体重。
结果
每个 ISA 的主要终点是通过多导睡眠图测量的替西帕肽和安慰剂组在第 52 周时呼吸暂停低通气指数反应的差异。次要终点包括睡眠呼吸暂停特异性缺氧负担、功能结果和心脏代谢生物标志物。该试验采用数字可穿戴设备，包括家庭睡眠测试以捕捉改善时间和加速度计评估日常体力活动，以评估探索性结果。
结论
SURMOUNT-OSA 采用新的设计来研究替西帕肽是否通过针对潜在病因为肥胖相关的 OSA 提供临床有意义的改善。
试验注册
ClinicalTrials.gov，NCT05412004。
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