近日，德国科隆大学Winfried Randerath团队研究了舒噻胺治疗阻塞性睡眠呼吸暂停症的疗效与安全性。相关论文于2025年10月9日发表在《柳叶刀》杂志上。

阻塞性睡眠呼吸暂停（OSA）非常普遍，但缺乏经批准的药物治疗方案。舒噻胺可通过抑制碳酸酐酶改善呼吸反应和上呼吸道肌肉活动。该研究旨在前瞻性评价三种剂量的舒噻胺治疗OSA的疗效和安全性。

这项多中心、随机、平行、双盲、安慰剂对照、剂量测定的2期试验在5个欧洲国家的28家医院和社区站点进行。将未经治疗、中度至重度OSA且呼吸暂停-低通气指数(AHI)≥15至≤50事件/小时的成人（18-75岁）随机分配（1:1:1:1:1），使用交互反应技术，每天睡前一次服用外观相同的安慰剂或舒噻胺100 mg、200 mg或300 mg片剂，持续15周。随机化按基线AHI3a分层。疗效的主要指标是AHI3a从基线到第15周（计划治疗结束）的相对变化。所有随机分配的参与者都被纳入使用估计框架的主要疗效分析和安全性分析。

2021年12月2日至2023年4月8日期间，研究组对535名患者进行了筛查，其中298名患者随机分配到安慰剂组（n=75），或舒噻胺100 mg （n=74）、200 mg （n=74）或300 mg组 （n=75）。240名患者完成了15周的治疗。298名参与者中有220名（74%）是男性，78名（26%）是女性。在完整的分析集中，安慰剂减去相对AHI3a调整后第15周舒噻胺100 mg、200 mg和300 mg组的平均变化分别为-16.4% (95% CI为- 33.1至- 1.4;p= 0.032), -30.2%（- 45.4至- 15.1;p< 0.0001）和34.6%(- 49.1至- 20.0;p< 0.0001) 。

不良事件发生率呈剂量依赖性增加：安慰剂组75例患者中46例（61%），舒噻胺100 mg组74例患者中54例（73%），舒噻胺200 mg组74例患者中62例（84%），舒噻胺300 mg组75例患者中68例（91%）。在安慰剂、舒噻胺100mg、200mg或300mg组中，超过10%的患者报告的事件是感觉异常（75例中有7例[9%]、74例中有16例[22%]、74例中有32例[43%]、75例中有43例[57%]）、头痛（6例[8%]、5例[7%]、12例[16%]、11例[15%]）、COVID-19（3例[4%]、3例[4%]、6例[8%]、10例[13%]）和鼻咽炎（9例[12%]、3例[4%]、7例[9%]、7例[9%]、7例[9%]）。

研究结果表明，舒噻胺可引起持续的、剂量依赖性的OSA、夜间缺氧、睡眠质量和日间过度嗜睡的改善。这些发现为阻塞性睡眠呼吸暂停患者的药物治疗提供了观点。

附：英文原文

Title: Sultiame once per day in obstructive sleep apnoea (FLOW): a multicentre, randomised, double-blind, placebo-controlled, dose-finding, phase 2 trial

Author: Winfried Randerath, Ludger Grote, Kaj Stenlf, Ingo Fietze, Julia Chevts, Erik Buntinx, Javier Albares, Katrin Kuhn, Corinna Hansen, Andreas Vlp, Jan Hedner, Dries Testelmans, Jean-Benoit Martinot, Farhad Baharloo, Benny Gimbada Mwenge, Erik Buntinx, Pierre Philip, Jean Louis Pepin, Frederic Gagnadoux, Maxime Patout, Maria Fernanda Troncoso Acevedo, Alejandro Iranzo de Riquer, Francisco Martinez-Orozco, Francisco Javier Puertas Cuesta, Ainhoa Alvarez Ruiz de Larrinaga, Francisco Javier Albares Tendero, Christian Viniol, Winfried Randerath, Heike Benes, Ingo Fietze, Geert Mayer, Katrin Gade, Christian Deckert, Peter Heymer, Frank Kaessner, Julia Chevts, Henning Candler, Zbysek Pavelek, Samuel Genzor

Issue&Volume: 2025-10-09

Abstract:

Background

Obstructive sleep apnoea (OSA) is highly prevalent but approved pharmacological treatment options are missing. Sultiame improves the ventilatory response and upper airway muscle activity by inhibiting carbonic anhydrase. This study aimed to prospectively assess the efficacy and safety of three dosages of sultiame in OSA.

Methods

This multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial was performed at 28 hospitals and community-based sites in five European countries. Adults (aged 18–75 years) with untreated, moderate to severe OSA and an Apnoea–Hypopnea Index (AHI) of ≥15 to ≤50 events per h were randomly assigned (1:1:1:1), using interactive response technology, to receive placebo or sultiame 100 mg, 200 mg, or 300 mg tablets of identical appearance once per day at bedtime for 15 weeks. Randomisation was stratified by baseline AHI3a. The primary outcome measure for efficacy was the relative change of AHI3a from baseline to week 15 (scheduled treatment end). All participants who were randomly assigned were included in the primary efficacy analysis using an estimands framework and in the safety analysis. This trial is registered with EudraCT (2021–002926–26) and ClinicalTrials.gov (NCT05236842) and is complete.

Findings

Between Dec 2, 2021, and April 8, 2023, 535 patients were screened and 298 were randomly assigned to placebo (n=75), or sultiame 100 mg (n=74), 200 mg (n=74), or 300 mg (n=75). 240 patients completed 15 weeks of treatment. 220 (74%) of 298 participants were male and 78 (26%) were female. In the full analysis set, placebo-subtracted relative AHI3a adjusted means change at week 15 was –16·4% (95% CI –31·3 to –1·4; p=0·032), –30·2% (–45·4 to –15·1; p<0·0001), and 34·6% (–49·1 to –20·0; p<0·0001) for sultiame 100 mg, 200 mg, and 300 mg, respectively. The incidence of adverse events increased dose-dependently: 46 (61%) of 75 patients in the placebo group, 54 (73%) of 74 in the 100 mg group, 62 (84%) of 74 in the 200 mg group, and 68 (91%) of 75 in the 300 mg group. Events reported in more than 10% of patients in the placebo, 100 mg, 200 mg, or 300 mg groups were paraesthesia (seven [9%] of 75, 16 [22%] of 74, 32 [43%] of 74, 43 [57%] of 75), headache (six [8%], five [7%], 12 [16%], 11 [15%]), COVID-19 (three [4%], three [4%], six [8%], ten [13%]), and nasopharyngitis (nine [12%], three [4%], seven [9%], seven [9%]).

Interpretation

Sultiame caused consistent, dose-dependent improvements of OSA, nocturnal hypoxia, sleep quality, and excessive daytime sleepiness. These findings offer perspectives for a pharmaceutical approach to treatment of patients with obstructive sleep apnoea.

DOI: 10.1016/S0140-6736(25)01196-1

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01196-1/abstract