Zolpidem on CPAP Acclimatization in OSA

Study Overview
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Brief Summary
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Obstructive sleep apnea (OSA) is a sleep disorder characterized by a cessation or significant decrease in airflow during sleep. CPAP is the preferred therapy and has high effectiveness at all levels of OSA severity. It acts as a pneumatic splint to maintain upper airway patency during sleep, preventing the soft tissues from collapsing. However, the patient's compliance continues to be an issue. One of the main contributors to CPAP therapy failure is difficulty falling asleep. To aid in the machine's adaptation, hypnotic medicine was administered.

Detailed Description
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Obstructive sleep apnea (OSA) is a sleep disorder characterized by a cessation or significant decrease in airflow during sleep. According to a recent study, OSA may impact over 1 billion individuals worldwide. In Thailand, the prevalence of snoring in children is 6.9-8.5%, while the prevalence of OSA in children is 0.7-1.3%. Moreover, OSA affects 15.4% of Thai male adults and 6.3% of Thai females. Untreated OSA can lead to daytime sleepiness, decreased productivity, increased motor vehicle accidents, and worsening hypertension, atrial fibrillation, and stroke. Oral appliances, upper airway surgery, and continuous positive airway pressure (CPAP) devices are available as treatment alternatives. CPAP is the preferred therapy and has high effectiveness at all levels of OSA severity. It acts as a pneumatic splint to maintain upper airway patency during sleep, preventing the soft tissues from collapsing. Through this mechanism, it effectively eliminates the apneas and/or hypopneas, decreases the arousals, and normalizes the oxygen saturation. However, the patient's compliance continues to be an issue. Failure of CPAP therapy may occur in up to 25% to 50% of patients, with patients typically discontinuing therapy within the first 2 to 4 weeks of treatment and 91% of patients discontinuing CPAP therapy within the first three years of therapy. According to the clinical guidelines of the American Academy of Sleep Medicine, all potential PAP titration candidates should receive adequate PAP education, hands-on demonstration, careful mask fitting, and acclimatization prior to titration. Acclimatization is a technique used to familiarize patients with PAP therapy for compliance. One of the main contributors to CPAP therapy failure is difficulty falling asleep. To aid in the machine's adaptation, hypnotic medicine was administered. Sedative medications now came in a variety of categories. Non-benzodiazepines sometimes referred to as Z-drugs, are among those with the beneficial characteristics of not deteriorating OSA severity, not contributing to drug addiction, possessing a rapid onset, and exhibiting fewer adverse consequences. Zolpidem, eszopiclone and zaleplon are included in this drug class. According to a previous meta-analysis, eszopiclone greatly facilitated the use of CPAP. However, up until now limited research on zolpidem and zaleplon was conducted. This study aims to evaluate the effect of zolpidem on CPAP compliance in OSA patients as compared to a placebo.

Official Title
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The Effect of Zolpidem on CPAP Acclimatization in Patients With OSA: A Crossover, Randomized, Double-blinded, Placebo-controlled Trial

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Drug: Zolpidem
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: OSA patients whose sleep test demonstrated apnea-hypopnea index (AHI) ≥ 15 /hour or AHI ≥ 5 /hour with comorbid disease including hypertension, cardiovascular disease, and stroke Age 18 to 75 years Indicated for CPAP therapy Naïve for the device usage Exclusion Criteria: A history of zolpidem allergies Currently take hypnotic medications Denied permission to engage in the study and/or follow its protocol Individuals with liver diseases, including hepatitis from any cause, liver cirrhosis, and liver cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The eligible participants will be informed and consented. After then, the participants in group 1 will receive 10 milligrams zolpidem contained in white-color opaque medicine capsule prepared by the pharmacist, meanwhile the participants in group 2 will receive placebo which is corn-starch contained in identical white-color opaque medicine capsule. The participants will be advised to take the medication 30 minutes prior to the bedtime until the 1-week follow up visit. On the second week, the participants in group 1 will alternatively receive placebo, meanwhile the participants in group 2 will receive 10 milligrams zolpidem in identical capsules. The wash-out period is 24 hours as the fact that the half-life of zolpidem is 2 hours and total zolpidem elimination time is 10 to 12 hours.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zolpidem<br>The participants in Zolpidem group will receive 10 milligrams zolpidem contained in white-color opaque medicine capsule prepared by the pharmacist. The participants will be advised to take the medication 30 minutes prior to the bedtime until the 1-week follow up visit. | Drug: Zolpidem<br>* 10 milligrams zolpidem contained in white-color opaque medicine capsule<br>|
| Placebo Comparator: Placebo<br>The participants in Placebo group will receive placebo which is corn-starch contained in identical white-color opaque medicine capsule. The participants will be advised to take the medication 30 minutes prior to the bedtime until the 1-week follow up visit. | Drug: Placebo<br>* corn-starch contained in identical white-color opaque medicine capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CPAP hour usage per night | CPAP hour usage per night in hours | on the end of the 1st as the 1st follow-up and the 2nd week as the 2nd follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numbers of the patients with CPAP usage ≥ 4 hours | Numbers of the patients with CPAP usage ≥ 4 hours in persons | on the end of the 1st as the 1st follow-up and the 2nd week as the 2nd follow-up | 
| Number of the participants with % CPAP usage ≥ 70 | Number of the participants with % CPAP usage ≥ 70 in persons | on the end of the 1st as the 1st follow-up and the 2nd week as the 2nd follow-up | 
| drug compliance, and adverse events | drug compliance with residual drug counts, and adverse events reports | on the end of the 1st as the 1st follow-up and the 2nd week as the 2nd follow-up |