Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial.
Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial.
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替泽帕肽治疗阻塞性睡眠呼吸暂停：SURMOUNT -OSA 3 期试验的基本原理、设计和样本基线特征。
DOI：
10.1016/j.cct.2024.107516
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发表时间：
2024
影响因子：
2.2
通讯作者：
Bunck,MathijsC
中科院分区：
文献类型：
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作者：
Malhotra,Atul;Bednarik,Josef;Chakladar,Sujatro;Dunn,JuliaP;Weaver,Terri;Grunstein,Ron;Fietze,Ingo;Redline,Susan;Azarbarzin,Ali;Sands,ScottA;Schwab,RichardJ;Bunck,MathijsC
背景减肥是肥胖或超重患者治疗阻塞性睡眠呼吸暂停 (OSA) 的标准建议；然而，如果不进行减肥手术，要实现和维持体重减轻可能具有挑战性。目前，尚无经批准的抗肥胖药物在 OSA 管理中显示出有效性。本研究正在评估替泽帕肽治疗肥胖症患者中度至重度 OSA 的有效性和安全性。方法 SURMOUNT-OSA 是一项随机、安慰剂对照、为期 52 周的 3 期试验，正在研究替泽帕肽治疗肥胖症参与者中度至重度 OSA（呼吸暂停低通气指数≥15 次事件/小时）的有效性和安全性 （体重指数≥30kg/m2）和明确的 OSA 诊断。 SURMOUNT-OSA 由 2 个干预特定附录 (ISA) 组成：ISA-1 包括当前未接受 OSA 治疗的参与者，ISA-2 包括使用气道正压治疗的参与者。总体而言，469 名参与者按照主方案按 1:1 随机分配接受替泽帕肽或安慰剂（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。结果各个 ISA 的主要终点是第 52 周时替西帕肽和安慰剂组之间通过多导睡眠图测量的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低氧负担、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，包括用于捕获改善时间的家庭睡眠测试和用于日常身体活动评估的加速度测量，以评估探索性结果。结论SURMOUNT-OSA 带来了一种新颖的设计，旨在研究替西帕肽是否通过针对潜在病因对肥胖相关 OSA 提供临床上有意义的改善。试验注册：ClinicalTrials.gov，NCT05412004
BackgroundWeight 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.MethodsSURMOUNT-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/m2) 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.ResultsThe 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.ConclusionSURMOUNT-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