Christopher N Schmickl, Jeremy E Orr, Raichel M Alex, Eli Gruenberg, Gabriela Parra, Stephanie White, Alex Spenceley, Tia DeSarkar, Mitchell Kong, Pamela N DeYoung, Scott A Sands, Robert L Owens, Atul Malhotra
{"title":"乙酰唑胺、艾司唑仑 +/- 文拉法辛治疗阻塞性睡眠呼吸暂停的联合药物疗法（RESCUE-Combo）：随机、双盲、安慰剂对照试验。","authors":"Christopher N Schmickl, Jeremy E Orr, Raichel M Alex, Eli Gruenberg, Gabriela Parra, Stephanie White, Alex Spenceley, Tia DeSarkar, Mitchell Kong, Pamela N DeYoung, Scott A Sands, Robert L Owens, Atul Malhotra","doi":"10.1513/AnnalsATS.202407-736OC","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Acetazolamide, eszopiclone, and venlafaxine may target different underlying mechanisms of obstructive sleep apnea (OSA) and individually may partially improve OSA severity in select patients. We tested whether acetazolamide+eszopiclone (DualRx) improves OSA severity. We further explored whether addition of venlafaxine (TripleRx) improves OSA in patients who do not fully respond to DualRx.</p><p><strong>Methods: </strong>In this double-blind, crossover trial, twenty OSA patients underwent a baseline polysomnography followed by DualRx/Placebo phases in random order. Subsequently, 18 patients underwent an open-label TripleRx phase. Each phase lasted 3 days and concluded with polysomnography. The primary outcome was the placebo-adjusted change in apnea-hypopnea index during supine, non-rapid eye movement sleep (AHINREM,supine) from baseline to DualRx. Secondary outcomes included other OSA metrics, sleep parameters, and select clinical outcomes (blood pressure, symptoms, vigilance).</p><p><strong>Results: </strong>Participants were on average middle-aged, overweight and relatively diverse (20% women, 60% non-white) with severe OSA (median [IQR] AHINREM,supine 32.8 [20-48.8] events/h). Compared with placebo, DualRx was well tolerated, improved the AHINREM,supine (-13.8 [-24.1 to -5.2] events/h or -45 [-77 to -14] %, PWilcoxon=0.003), AHIOverall, hypoxic burden and sleep architecture (P<0.05), but not the selected clinical outcomes. TripleRx did not provide a clear benefit relative to DualRx, although some measures of OSA-related hypoxemia improved more substantially. There were no serious side effects.</p><p><strong>Discussion: </strong>Short-term use of dual-drug therapy with acetazolamide+eszopiclone substantially improved OSA severity. Adding venlafaxine did not generally improve OSA severity but may be beneficial for some patients. Longer term studies are needed to assess effects on clinically important outcomes. Clinical trial registration available at www.</p><p><strong>Clinicaltrials: </strong>gov, ID: NCT04639193.</p>","PeriodicalId":93876,"journal":{"name":"Annals of the American Thoracic Society","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Combination Drug Therapy with Acetazolamide, Eszopiclone +/- Venlafaxine for Obstructive Sleep Apnea (RESCUE-Combo): A Randomized, Double-blind, Placebo-controlled Trial.\",\"authors\":\"Christopher N Schmickl, Jeremy E Orr, Raichel M Alex, Eli Gruenberg, Gabriela Parra, Stephanie White, Alex Spenceley, Tia DeSarkar, Mitchell Kong, Pamela N DeYoung, Scott A Sands, Robert L Owens, Atul Malhotra\",\"doi\":\"10.1513/AnnalsATS.202407-736OC\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Acetazolamide, eszopiclone, and venlafaxine may target different underlying mechanisms of obstructive sleep apnea (OSA) and individually may partially improve OSA severity in select patients. 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Secondary outcomes included other OSA metrics, sleep parameters, and select clinical outcomes (blood pressure, symptoms, vigilance).</p><p><strong>Results: </strong>Participants were on average middle-aged, overweight and relatively diverse (20% women, 60% non-white) with severe OSA (median [IQR] AHINREM,supine 32.8 [20-48.8] events/h). Compared with placebo, DualRx was well tolerated, improved the AHINREM,supine (-13.8 [-24.1 to -5.2] events/h or -45 [-77 to -14] %, PWilcoxon=0.003), AHIOverall, hypoxic burden and sleep architecture (P<0.05), but not the selected clinical outcomes. TripleRx did not provide a clear benefit relative to DualRx, although some measures of OSA-related hypoxemia improved more substantially. There were no serious side effects.</p><p><strong>Discussion: </strong>Short-term use of dual-drug therapy with acetazolamide+eszopiclone substantially improved OSA severity. Adding venlafaxine did not generally improve OSA severity but may be beneficial for some patients. Longer term studies are needed to assess effects on clinically important outcomes. Clinical trial registration available at www.</p><p><strong>Clinicaltrials: </strong>gov, ID: NCT04639193.</p>\",\"PeriodicalId\":93876,\"journal\":{\"name\":\"Annals of the American Thoracic Society\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-11-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of the American Thoracic Society\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1513/AnnalsATS.202407-736OC\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of the American Thoracic Society","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1513/AnnalsATS.202407-736OC","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
简介：乙酰唑胺、艾司唑仑和文拉法辛可能针对阻塞性睡眠呼吸暂停（OSA）的不同潜在机制，单独使用可部分改善特定患者的 OSA 严重程度。我们测试了乙酰唑胺+依佐匹克隆（DualRx）是否能改善 OSA 的严重程度。我们还进一步探讨了加用文拉法辛（TripleRx）是否能改善对 DualRx 反应不完全的患者的 OSA：在这项双盲交叉试验中，20 名 OSA 患者接受了基线多导睡眠图检查，然后按照随机顺序接受了 DualRx/安慰剂治疗。随后，18 名患者接受了开放标签 TripleRx 阶段治疗。每个阶段持续 3 天，最后进行多导睡眠监测。主要结果是安慰剂调整后的仰卧非快速眼动睡眠时呼吸暂停-低通气指数（AHINREM,仰卧）从基线到 DualRx 的变化。次要结果包括其他 OSA 指标、睡眠参数和部分临床结果（血压、症状、警觉性）：参与者平均年龄为中年，体重超重，相对多样化（20% 为女性，60% 为非白人），患有严重 OSA（中位数 [IQR] AHINREM，仰卧 32.8 [20-48.8] 事件/小时）。与安慰剂相比，DualRx 的耐受性良好，改善了仰卧位 AHINREM（-13.8 [-24.1 至 -5.2]事件/小时或-45 [-77 至 -14]%，PWilcoxon=0.003）、AHIOverall、缺氧负担和睡眠结构（PDiscussion：短期使用乙酰唑胺+依佐匹克隆双药治疗可显著改善 OSA 的严重程度。加入文拉法辛一般不会改善 OSA 的严重程度，但可能对某些患者有益。需要进行更长期的研究，以评估对临床重要结果的影响。临床试验注册请访问 www.Clinicaltrials: gov，ID：NCT04639193。
Combination Drug Therapy with Acetazolamide, Eszopiclone +/- Venlafaxine for Obstructive Sleep Apnea (RESCUE-Combo): A Randomized, Double-blind, Placebo-controlled Trial.
Introduction: Acetazolamide, eszopiclone, and venlafaxine may target different underlying mechanisms of obstructive sleep apnea (OSA) and individually may partially improve OSA severity in select patients. We tested whether acetazolamide+eszopiclone (DualRx) improves OSA severity. We further explored whether addition of venlafaxine (TripleRx) improves OSA in patients who do not fully respond to DualRx.
Methods: In this double-blind, crossover trial, twenty OSA patients underwent a baseline polysomnography followed by DualRx/Placebo phases in random order. Subsequently, 18 patients underwent an open-label TripleRx phase. Each phase lasted 3 days and concluded with polysomnography. The primary outcome was the placebo-adjusted change in apnea-hypopnea index during supine, non-rapid eye movement sleep (AHINREM,supine) from baseline to DualRx. Secondary outcomes included other OSA metrics, sleep parameters, and select clinical outcomes (blood pressure, symptoms, vigilance).
Results: Participants were on average middle-aged, overweight and relatively diverse (20% women, 60% non-white) with severe OSA (median [IQR] AHINREM,supine 32.8 [20-48.8] events/h). Compared with placebo, DualRx was well tolerated, improved the AHINREM,supine (-13.8 [-24.1 to -5.2] events/h or -45 [-77 to -14] %, PWilcoxon=0.003), AHIOverall, hypoxic burden and sleep architecture (P<0.05), but not the selected clinical outcomes. TripleRx did not provide a clear benefit relative to DualRx, although some measures of OSA-related hypoxemia improved more substantially. There were no serious side effects.
Discussion: Short-term use of dual-drug therapy with acetazolamide+eszopiclone substantially improved OSA severity. Adding venlafaxine did not generally improve OSA severity but may be beneficial for some patients. Longer term studies are needed to assess effects on clinically important outcomes. Clinical trial registration available at www.
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