随机对照试验索里昂氨酯治疗 OSA 患者日间过度嗜睡：OSA 治疗依从或不依从亚组分析。

Randomized Controlled Trial of Solriamfetol for Excessive Daytime Sleepiness in OSA: An Analysis of Subgroups Adherent or Nonadherent to OSA Treatment.

机构信息

Sleep Medicine and Research Center, St. Luke's Hospital, Chesterfield, MO.

Department of Neurology, Hephata Klinik, Schwalmstadt, Germany.

出版信息

Chest. 2021 Jul;160(1):307-318. doi: 10.1016/j.chest.2021.02.033. Epub 2021 Feb 22.

BACKGROUND

Solriamfetol, a dopamine-norepinephrine reuptake inhibitor, is approved in the United States to improve wakefulness in adults with excessive daytime sleepiness (EDS) associated with OSA (37.5-150 mg/d).

RESEARCH QUESTION

Does solriamfetol have differential effects on EDS based on adherence to primary OSA therapy and does solriamfetol affect primary OSA therapy use?

STUDY DESIGN AND METHODS

Participants were randomized to 12 weeks of placebo or solriamfetol 37.5, 75, 150, or 300 mg/d (stratified by primary OSA therapy adherence). Coprimary end points were week 12 change from baseline in 40-min Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) in the modified intention-to-treat population. Primary OSA therapy use (hours per night, % nights) and safety were evaluated.

RESULTS

At baseline, 324 participants (70.6%) adhered to OSA therapy (positive airway pressure use ≥ 4 h/night on ≥ 70% nights, surgical intervention, or oral appliance use on ≥ 70% nights) and 135 participants (29.4%) did not adhere. Least squares (LS) mean differences from placebo in MWT sleep latency (minutes) in the 37.5-, 75-, 150-, and 300-mg/d groups among adherent participants were 4.8 (95% CI, 0.6-9.0), 8.4 (95% CI, 4.3-12.5), 10.2 (95% CI, 6.8-13.6), and 12.5 (95% CI, 9.0-15.9) and among nonadherent participants were 3.7 (95% CI, -2.0 to 9.4), 9.9 (95% CI, 4.4-15.4), 11.9 (95% CI, 7.5-16.3), and 13.5 (95% CI, 8.8-18.3). On ESS, LS mean differences from placebo in the 37.5-, 75-, 150-, and 300-mg/d groups among adherent participants were -2.4 (95% CI, -4.2 to -0.5), -1.3 (95% CI, -3.1 to 0.5), -4.2 (95% CI, -5.7 to -2.7), and -4.7 (95% CI, -6.1 to -3.2) and among nonadherent participants were -0.7 (95% CI, -3.5 to 2.1), -2.6 (95% CI, -5.4 to 0.1), -5.0 (95% CI, -7.2 to -2.9), and -4.6 (95% CI, -7.0 to -2.3). Common adverse events included headache, nausea, anxiety, decreased appetite, nasopharyngitis, and diarrhea. No clinically meaningful changes were seen in primary OSA therapy use with solriamfetol.

INTERPRETATION

Solriamfetol improved EDS in OSA regardless of primary OSA therapy adherence. Primary OSA therapy use was unaffected with solriamfetol.

TRIAL REGISTRY

ClinicalTrials.gov; No.: NCT02348606; URL: www.clinicaltrials.gov; EU Clinical Trials Register; No.: EudraCT2014-005514-31; URL: www.clinicaltrialsregister.eu.

背景

索利那新是一种多巴胺-去甲肾上腺素再摄取抑制剂，在美国被批准用于改善与 OSA 相关的白天过度嗜睡（EDS）成年人的觉醒状态（37.5-150mg/d）。

研究问题

索利那新是否会根据对原发性 OSA 治疗的依从性对 EDS 产生不同的影响，以及索利那新是否会影响原发性 OSA 治疗的使用？

研究设计和方法

参与者被随机分配到安慰剂或索利那新 37.5、75、150 或 300mg/d 的 12 周治疗组（按原发性 OSA 治疗的依从性分层）。主要终点是在改良意向治疗人群中，从基线到第 12 周的 40 分钟维持觉醒试验（MWT）和 Epworth 睡眠量表（ESS）的变化。评估了原发性 OSA 治疗的使用（每夜小时数，%n 夜）和安全性。

结果

在基线时，324 名参与者（70.6%）依从 OSA 治疗（正压通气治疗≥4 小时/夜，≥70%的夜间；手术干预或口腔器械治疗≥70%的夜间），135 名参与者（29.4%）不依从。在依从治疗的参与者中，与安慰剂相比，37.5、75、150 和 300mg/d 组的 MWT 睡眠潜伏期（分钟）的最小二乘（LS）平均差异分别为 4.8（95%CI，0.6-9.0）、8.4（95%CI，4.3-12.5）、10.2（95%CI，6.8-13.6）和 12.5（95%CI，9.0-15.9），在不依从治疗的参与者中，LS 平均差异分别为 3.7（95%CI，-2.0 至 9.4）、9.9（95%CI，4.4 至 15.4）、11.9（95%CI，7.5 至 16.3）和 13.5（95%CI，8.8 至 18.3）。在 ESS 方面，与安慰剂相比，37.5、75、150 和 300mg/d 组的 LS 平均差异在依从治疗的参与者中分别为-2.4（95%CI，-4.2 至-0.5）、-1.3（95%CI，-3.1 至 0.5）、-4.2（95%CI，-5.7 至-2.7）和-4.7（95%CI，-6.1 至-3.2），在不依从治疗的参与者中分别为-0.7（95%CI，-3.5 至 2.1）、-2.6（95%CI，-5.4 至 0.1）、-5.0（95%CI，-7.2 至-2.9）和-4.6（95%CI，-7.0 至-2.3）。常见的不良反应包括头痛、恶心、焦虑、食欲下降、鼻咽部炎症和腹泻。索利那新对原发性 OSA 治疗的使用没有明显的影响。