Chloral Hydrate in the Treatment of Severe Insomnia When Other Treatments Have Failed: Results From a Real-World Evidence Study (RESTORE).

STUDY

OBJECTIVES

The efficacy and safety of chloral hydrate, used as approved for severe insomnia in the UK, were assessed in a single-arm, open-label, real-world, decentralized clinical trial using contemporary self-reported outcome measures.

METHODS

Participants (18-75 years) had clinically significant impairment by severe insomnia (Insomnia Severity Index (ISI) score of 20-28), and history of behavioral and pharmacological sleep therapy failure. Specialists confirmed the clinical diagnosis and prescribed chloral hydrate (500 mg/5 mL oral solution, 430 or 860 mg daily) for 2 weeks followed by a 4-week follow-up period. Endpoints included change in ISI score from confirmatory diagnosis to treatment end (primary); and sleep measures, health-related quality of life (HRQoL), anxiety, depression, and adverse events (AEs; secondaries).

RESULTS

Of the 96 participants (mean baseline ISI, 24.03 [SD, 2.06]), 85 completed the study. Improvements were observed with ISI at treatment end (week 2 mean change was -10.79 [95% confidence interval, -12.12, -9.47]; n=93; week 6 mean change was -8.04 (95% confidence interval, -9.13, -6.95; p < 0.0001; n=85), exceeding the 6-point change considered a minimal clinically important difference. Self-reported sleep measures including Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index, HRQoL, and anxiety shows significant improvements during treatment with some outcomes indicating continued benefit up to 4 weeks post-treatment. Most treatment-related AEs were mild in nature (83.9%, 256/305 events) including wind (73.9%), headache (58.7%), and stomach pain (31.5%). While no events met criteria for serious or severe intensity, seven participants (7.6%) withdrew owing to AEs.

CONCLUSION

Short-term UK-approved chloral hydrate may provide a potential option for severe adult insomnia only when prior treatments have failed.

TRIAL REGISTRATION: NCT06053840 (https://clinicaltrials.gov); ISRCTN10433315 (https://www.isrctn.com/).