MedPath

Prospective Observational Study on the Effectiveness of Daridorexant in Chronic Insomnia in a Real-World Setting

Completed
Conditions
Insomnia Chronic
Registration Number
NCT07132086
Lead Sponsor
Azienda Ospedaliero, Universitaria Pisana
Brief Summary

The primary objectives of this study is to evaluate the real-world effectiveness of daridorexant 50 mg in improving both subjective (self-report) and objective (actigraphic) sleep parameters in patients with chronic insomnia.

The secondary aims of this study are:

* To compare the effectiveness of daridorexant 50 mg with other guideline-recommended therapies for chronic insomnia in improving sleep parameters and sleep health.

* To identify clinical and demographic predictors of response to daridorexant 50 mg, such as age, sex, BMI, duration of insomnia, and treatment regimen (monotherapy vs. add-on).

* To monitor changes over time in the symptoms related to comorbid sleep disorders (e.g., OSA, RLS, circadian rhythm disorders) in patients treated with daridorexant 50 mg.

Detailed Description

Insomnia affects approximately 10% of the European population and represents a significant risk factor for multiple chronic conditions, including cardiovascular diseases, depression, and type II diabetes. The latest European Guidelines for the Management of Insomnia have included daridorexant among the first-line pharmacological options for chronic insomnia. Daridorexant is a dual orexin receptor antagonist (DORA) that offers advantages over traditional hypnotics by avoiding common adverse effects such as residual daytime sedation, impaired motor coordination, and the risk of dependence.

Clinical trials have demonstrated that DORAs, including daridorexant, are effective in improving several subjective and objective sleep parameters. However, no studies to date have investigated predictors of treatment response in patients with insomnia receiving daridorexant, despite increasing awareness of the need for personalized pharmacological strategies.

In pivotal trials, daridorexant efficacy was evaluated using both subjective (patient-reported) and objective (polysomnographic) sleep outcomes. While polysomnography (PSG) is the gold standard for objective sleep evaluation, it is poorly suited for long-term, real-world monitoring due to cost, complexity, and reduced ecological validity. In contrast, actigraphy allows for non-invasive, home-based sleep-wake monitoring through wrist movement detection over multiple nights and is widely used in sleep research and clinical settings. However, no studies have employed actigraphy to assess daridorexant's real-world effectiveness, leaving a significant knowledge gap.

Another relevant aspect is the frequent co-occurrence of insomnia with other sleep disorders such as restless legs syndrome (RLS), circadian rhythm sleep-wake disorders, and obstructive sleep apnea (OSA). Evaluating the evolution of symptoms related to these comorbid sleep conditions in patients treated with daridorexant could help clarify whether its use should be expanded or restricted in certain clinical populations.

Study Objectives and Outcome Measures

Primary Objectives:

To evaluate the real-world effectiveness of daridorexant 50 mg in improving both subjective (questionnaire-based) and objective (actigraphy-based) sleep parameters in patients with chronic insomnia.

Secondary Objectives:

To compare the effectiveness of daridorexant 50 mg with other guideline-recommended therapies for chronic insomnia in improving sleep parameters and sleep health.

To identify clinical and demographic predictors of response to daridorexant 50 mg, such as age, sex, BMI, duration of insomnia, and treatment regimen (monotherapy vs. add-on).

To monitor changes over time in the symptoms related to comorbid sleep disorders (e.g., OSA, RLS, circadian rhythm disorders) in patients treated with daridorexant 50 mg.

Primary Endpoint:

This is the first prospective observational study aiming to assess the real-world effectiveness of daridorexant 50 mg in improving both subjective and actigraphic sleep parameters in patients with chronic insomnia. In addition, the study will evaluate possible changes in circadian metrics over time, with the goal of better understanding the impact of daridorexant on patients' sleep-wake rhythm under real-life conditions.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
31
Inclusion Criteria
  • Age ≥ 18 years
  • Signed informed consent form
  • Diagnosis of chronic insomnia according to DSM-5 criteria, defined as:

Dissatisfaction with sleep quantity or quality, associated with one or more of the following:

Difficulty initiating sleep

Difficulty maintaining sleep (frequent awakenings or trouble returning to sleep)

Early morning awakenings with inability to return to sleep

The sleep disturbance causes clinically significant distress or impairment in social, occupational, educational, academic, or other important areas of functioning

Sleep difficulties occur despite adequate opportunity and circumstances for sleep

The insomnia is not better explained by or occurring exclusively during other sleep-wake disorders (e.g., narcolepsy, parasomnias, circadian rhythm sleep-wake disorders, breathing-related sleep disorders)

The insomnia is not attributable to the physiological effects of a substance (e.g., drug abuse or medication)

  • No contraindications to daridorexant use according to the European Medicines Agency (EMA)
Exclusion Criteria
  • Pregnancy
  • Breastfeeding
  • Withdrawal of informed consent at any time

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Change in total sleep time after 3 months of daridorexant treatmentFrom baseline (Day 0) to 3 months after treatment initiation

This outcome assesses the change in both subjective (patient-reported) and objective (actigraphic) total sleep time (TST) from baseline to 3 months after initiating daridorexant 50 mg.

Primary Outcome Measures:

* Change in subjective TST \[minutes/night\]

* Change in actigraphic TST \[minutes/night\]

Change in wake after sleep onset after 3 months of daridorexant treatmentFrom baseline (Day 0) to 3 months after treatment initiation

This outcome assesses the change in both subjective (patient-reported) and objective (actigraphic) wake after sleep onset (WASO) from baseline to 3 months after initiating daridorexant 50 mg.

Primary Outcome Measures:

* Change in subjective WASO \[minutes/night\]

* Change in actigraphic WASO \[minutes/night\]

Change in sleep efficiency after 3 months of daridorexant treatmentFrom baseline (Day 0) to 3 months after treatment initiation

This outcome assesses the change in both subjective (patient-reported) and objective (actigraphic) sleep efficiency (SE) from baseline to 3 months after initiating daridorexant 50 mg.

Primary Outcome Measures:

* Change in subjective SE. Subjective SE is estimated as the ratio of subjective TST to Time in bed \[%\]

* Change in actigraphic SE. Actigraphic SE is estimated as the ratio of actigraphic TST to Time in bed \[%\]

Change in sleep regularity index after 3 months of daridorexant treatmentFrom baseline (Day 0) to 3 months after treatment initiation

This outcome assesses the change in objective (actigraphic) sleep regularity index (SRI) from baseline to 3 months after initiating daridorexant 50 mg.

Primary Outcome Measure:

- Change in Sleep Regularity Index (SRI) \[%\]

Change in self-reported sleep questionnaires after 3 months of daridorexant treatmentFrom baseline (Day 0) to 3 months after treatment initiation

This outcome assesses the change in self-reported sleep questionnaires from baseline to 3 months after initiating daridorexant 50 mg.

Primary Outcome Measures:

* Change in sleep quality (PSQI score) \[range: 0-21\]

* Change in insomnia severity (ISI score) \[range: 0-28\]

* Change in daytime functioning and alertness (IDSIQ total score) \[range: 0-100\]

Secondary Outcome Measures
NameTimeMethod
Change in TST misperception after 3 months of daridorexant treatmentFrom baseline (Day 0) to 3 months after treatment initiation

This outcome assesses the change in TST misperception from baseline to 3 months after initiating daridorexant 50 mg.

TST misperception is calculated as the difference between subjective and actigraphic TST (hours)

Change in SE misperception after 3 months of daridorexant treatmentFrom baseline (Day 0) to 3 months after treatment initiation

This outcome assesses the change in SE misperception from baseline to 3 months after initiating daridorexant 50 mg.

SE misperception is calculated as the difference between subjective and actigraphic SE (%)

Change in WASO misperception after 3 months of daridorexant treatmentFrom baseline (Day 0) to 3 months after treatment initiation

This outcome assesses the change in WASO misperception from baseline to 3 months after initiating daridorexant 50 mg.

WASO misperception is calculated as the difference between subjective and actigraphic WASO (minutes)

Trial Locations

Locations (1)

Azienda Ospedaliera Universitaria Pisana

🇮🇹

Pisa, Pi, Italy

Azienda Ospedaliera Universitaria Pisana
🇮🇹Pisa, Pi, Italy

MedPath

Empowering clinical research with data-driven insights and AI-powered tools.

© 2025 MedPath, Inc. All rights reserved.