Results of the SHARP Study: A Randomized, Placebo-Controlled, Double-Blind, Repeated-Measures, Crossover, Phase IV Clinical Trial of the Effect of the Wake-Promoting Agent Solriamfetol on Cognitive Function in Obstructive Sleep Apnea With Excessive Daytime Sleepiness and Cognitive Impairment.

IF 9.5 1区医学 Q1 CRITICAL CARE MEDICINE

Chest Pub Date : 2024-11-09 DOI:10.1016/j.chest.2024.10.050

Hans P A Van Dongen, Eileen B Leary, Christopher Drake, Richard Bogan, Judith Jaeger, Russell Rosenberg, Caroline Streicher, Herriot Tabuteau

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引用次数: 0

Abstract

Background: Obstructive sleep apnea (OSA) causes episodes of fragmented sleep and intermittent hypoxia and leads to excessive daytime sleepiness (EDS). Deficits in cognitive function are a troublesome symptom in patients with OSA and EDS.

Research question: How does solriamfetol affect cognitive function in patients with cognitive impairment associated with OSA and EDS?

Study design and methods: SHARP was a phase 4, randomized, double-blind, placebo-controlled, crossover trial. Participants (N=59) were randomized to receive placebo or solriamfetol (75 mg/day for 3 days, then 150 mg/day) for 2 weeks, with crossover separated by a 1-week washout. Efficacy measures included the Coding subtest, comparable to the Digit Symbol Substitution Test, of the Repeatable Battery for the Assessment of Neuropsychological Status (DSST RBANS), the British Columbia Cognitive Complaints Inventory (BC-CCI), Patient Global Impression of Severity (PGI-S), and Epworth Sleepiness Scale (ESS). The primary endpoint was change from baseline in average post-dose DSST RBANS scores. Secondary endpoints were changes from baseline in BC-CCI, PGI-S, ESS, and DSST RBANS scores at 2, 4, 6, and 8 hours post-dose. Safety was monitored by treatment-emergent adverse events (TEAEs).

Results: Solriamfetol significantly improved post-dose average DSST RBANS scores compared with placebo (P=0.009; effect size [Cohen's d] 0.37). When evaluated at each 2-hour timepoint, cognitive function was significantly improved at 2, 6, and 8 hours after dosing (all P<0.05). During solriamfetol treatment, there were significant improvements in BC-CCI (P=0.002; d=0.45), PGI-S (P=0.0mixed; d=0.29), and ESS (P=0.004; d=0.40) compared with placebo. The most common TEAEs were nausea (7%) and anxiety (3%).

Interpretation: SHARP demonstrated that solriamfetol can improve objective and subjective measures of cognitive function in patients with cognitive impairment associated with OSA and EDS.

Clinical trial registration: NCT04789174; EudraCT: 2020-004243-92.

查看原文本刊更多论文

SHARP 研究结果：一项随机、安慰剂对照、双盲、重复测量、交叉的 IV 期临床试验，研究促醒剂 Solriamfetol 对伴有白天过度嗜睡和认知功能障碍的阻塞性睡眠呼吸暂停患者认知功能的影响。

背景：阻塞性睡眠呼吸暂停（OSA）会导致睡眠碎片化和间歇性缺氧，并导致白天过度嗜睡（EDS）。认知功能缺陷是 OSA 和 EDS 患者的一个令人头疼的症状：研究问题：索利安非托对伴有 OSA 和 EDS 的认知功能障碍患者的认知功能有何影响？SHARP是一项第4期随机、双盲、安慰剂对照交叉试验。参试者（59 人）被随机分配接受安慰剂或索利安非托（75 毫克/天，连续 3 天，然后 150 毫克/天）治疗，为期 2 周，交叉治疗间隔 1 周。疗效测量包括神经心理状态评估可重复性电池（DSST RBANS）的编码子测试（与数字符号替换测试相当）、不列颠哥伦比亚认知抱怨量表（BC-CCI）、患者对严重程度的总体印象（PGI-S）和埃普沃斯嗜睡量表（ESS）。主要终点是用药后 DSST RBANS 平均得分与基线相比的变化。次要终点是用药后 2、4、6 和 8 小时 BC-CCI、PGI-S、ESS 和 DSST RBANS 评分与基线相比的变化。安全性通过治疗突发不良事件（TEAEs）进行监测：与安慰剂相比，索利安非妥能明显改善服药后的DSST RBANS平均得分（P=0.009；效应大小[Cohen's d] 0.37）。在每个 2 小时时间点进行评估时，用药后 2、6 和 8 小时的认知功能均有明显改善（所有 P 均为 0.009）：SHARP表明，索利安非托尔能改善伴有OSA和EDS的认知功能障碍患者的客观和主观认知功能：临床试验注册：NCT04789174；EudraCT：2020-004243-92。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chest 医学-呼吸系统

CiteScore

13.70

自引率

3.10%

发文量

3369

审稿时长

15 days

期刊介绍： At CHEST, our mission is to revolutionize patient care through the collaboration of multidisciplinary clinicians in the fields of pulmonary, critical care, and sleep medicine. We achieve this by publishing cutting-edge clinical research that addresses current challenges and brings forth future advancements. To enhance understanding in a rapidly evolving field, CHEST also features review articles, commentaries, and facilitates discussions on emerging controversies. We place great emphasis on scientific rigor, employing a rigorous peer review process, and ensuring all accepted content is published online within two weeks.