Daridorexant intervention in non-invasive positive pressure ventilation treatment for patients with comorbid insomnia and obstructive sleep apnea: a study protocol

Background

Insomnia and obstructive sleep apnea are the two most common sleep disorders. Their comorbidity is termed “Comorbid Insomnia and Obstructive Sleep Apnea (COMISA).” Compared to patients with a single disorder, those with COMISA have significantly increased risks of functional impairment, complications, and all-cause mortality. Although non-invasive positive pressure ventilation (NPPV), such as continuous positive airway pressure (CPAP), is the first-line treatment for moderate-to-severe obstructive sleep apnea, low adherence remains a major challenge, primarily due to patient discomfort caused by the first-night effect, which leads to reduced compliance. Patients with COMISA show 30% lower adherence to NPPV than those with obstructive sleep apnea (OSA) alone. Daridorexant is considered a potential new treatment option. Millimeter-wave radar sleep monitoring technology and digital insomnia management systems have been widely used for whole-course disease tracking and management. Therefore, this study aims to investigate the efficacy and safety of daridorexant in improving adherence to NPPV in patients with COMISA.

Methods

We plan to conduct a multicenter, prospective, randomized controlled trial (RCT) in patients with COMISA. The trial will be carried out at the Affiliated Nanhua Hospital of the University of South China and other collaborating hospitals. After obtaining informed consent, 120 participants will be randomly assigned to one of four conditions: (1) conventional ventilator therapy alone; (2) ventilator therapy + daridorexant 25 mg; (3) ventilator therapy + daridorexant 50 mg; (4) ventilator therapy + placebo. Daridorexant will be used for the treatment of mild, moderate, and severe COMISA patients according to clinical guidelines. Millimeter-wave radar sleep monitoring devices and digital follow-up systems will be introduced to achieve whole-course tracking and management of COMISA patients. Participants will be guided by trained physicians, nurses, and researchers at the hospital to complete treatment and follow-up. The primary outcomes include the efficacy of daridorexant in improving sleep quality, its safety and tolerability, improvement of the first-night effect associated with ventilator use, and adherence as well as adherence duration. Secondary outcomes include the incidence of cardiovascular and cerebrovascular complications (hypertension, stroke, myocardial infarction) during the 3-year follow-up period, the correlation between millimeter-wave radar monitoring parameters and ventilator data, and the impact of stratified outcome reports (significant, moderate, or poor efficacy) on patients’ behavioral changes. Outcome variables will be assessed by comparing baseline (T0) with measurements at 1 week (T1), 1 month (T2), 3 months (T3), 1 year (T4), and 3 years (T5). Discussion:This study fills a gap regarding the use of dual orexin receptor antagonists as an intervention to support NPPV in patients with COMISA. Furthermore, the study will evaluate the benefits of reducing cardiovascular and cerebrovascular complications (hypertension, stroke, myocardial infarction) during follow-up, as well as the effects on behavioral changes. Estimating treatment responses based on individual differences, including COMISA severity, may provide insights for precision medicine in the treatment of COMISA.

No conflicts of interest.

References

No references