Effects of Continuous Positive Airway Pressure Therapy Withdrawal in Patients With Obstructive Sleep Apnea: A Randomized Trial

Study design (e.g., double-blind:

A randomized, open-labeled, controlled, parallel-group study.

Sixty patients will be recruited with moderate to severe Obstructive Sleep Apnea (OSA), previously adherent to CPAP therapy and have controlled OSA defined as Apnea Hypopnea Index (AHI) of < 5 while on treatment. Patients will be divided into two groups after completion of Therapeutic CPAP, Who will continue on same CPAP therapy for 4 weeks they will be randomized into two groups:

1. NO CPAP (NOCPAP Group): Who will stop using the CPAP device.
2. Intermittent CPAP (Int-CPAP Group): Who will use the CPAP device every other night.

This trial will also evaluate the effects of CPAP withdrawal (complete or partial) on excessive day time sleepiness (EDS), apnea hypopnea index (AHI), Heart Rate and Blood Pressure.

Study Overview

• Status: Recruiting
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Device: Withdrawal of Continuous Positive Airway Pressure device; Device: Alternation usage of Continuous Positive Airway Pressure Device

Detailed Description

Obstructive sleep apnea syndrome (OSAS) is a common sleep-related breathing disorder, which is characterized by transient interruption of ventilation during sleep caused by complete or partial collapse of the upper airway. Many risk factors are identified such as: male gender, large neck circumference, smoking, excessive alcohol intake and high Body Mass Index (BMI).

The prevalence of OSAS in Saudi Arabia is about 4% and 1.8% in males and females, respectively, and it is associated with many comorbidities like type 2 DM, ischemic heart disease, congestive heart failure, hypertension and depression.

Continuous positive airway pressure (CPAP) is considered the gold standard treatment for moderate to severe (OSA) as it works as a pneumatic splint of the collapsible airway and it may induce anatomical and functional changes of the upper air way muscles. Treatment with CPAP was reported to decrease daytime sleepiness, and improve the quality of life among sleep apnea patients. However, its impact on other outcomes such as hypertension was modest but clinically significant and it may has no impact on other major cardiovascular outcomes such as cardiovascular mortality, acute coronary syndrome, stroke, transient ischemic attack or hospitalization for heart failure even in patients with established coronary artery disease, and the same result was seen in two recently published meta-analyses.

The widely used definition of acceptable adherence to the CPAP is 4 hours per night for more than 70% of all monitored days or 5 days per week. However, this definition was based on experts' opinion and the knowledge about human sleep. Many studies showed that the 4 hours cut-off was the minimum required amount of time to gain significant improvement from CPAP use and there was a linear dose response relationship with greater benefit observed with increasing nightly use.

However, few studies conducted to assess the effect of CPAP withdrawal following long term treatment of OSAS with conflicting results. The residual effects of CPAP after withdrawal has been controversial in the medical literature. Although some studies suggest that there is some form of reversibility associated with CPAP compliance which leads to improvement in subjective and objective assessment of sleepiness, however, other reports revealed that CPAP withdrawal is associated with a rapid recurrence of OSAS. Rossi et al reported that in 71% of the study population, CPAP withdrawal for four nights was associated with relapse of OSA. However, 10 % remained in remission after 2 weeks of treatment withdrawal. Moreover, we could not find a study that evaluated an intermittent CPAP therapy after a long period of adherence. However, Issa & Sullivan reported that after 2-3 month of daily CPAP use, patients who use CPAP on intermittent 3-4 nights "on" and 2-3 nights "off were able to maintain good day time function, which maybe a reflection of a less fragmented sleep, thus an adequately controlled OSAS.

Nevertheless, the withdrawal of CPAP raises an ethical concern. However, several reports support the relieve from this fear. Studies of Short-term CPAP withdrawal revealed that it was not associated with any impairment of coronary endothelial function, or raise of stress hormones and markers of vascular inflammation. In addition, the recent Australian and the SAVE studies that were quoted before revealed no significant effect of CPAP on preventing secondary cardiovascular diseases.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Siraj O Wali, Professor; Phone Number: 16045 0126408222; Email: sowali@kau.edu.sa

Study Locations

• Saudi Arabia
  • Jeddah, Saudi Arabia, 22230
    • Recruiting
    • King AbdulAziz University Hospital
    • Contact: Siraj O Wali, Professor; Phone Number: 1640 0126408222; Email: sowali@kau.edu.sa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 20 and 75 years, AHI > 15 based on PSG An Epworth Sleepiness Scale (ESS) of >10, (At base line before treatment ) Stable BMI: defines as BMI that has been stable with no more than 10 % changes. Currently on CPAP therapy for more than or equal of 6 months Compliance with CPAP defined as more than 4 hours per night for an average of 5 nights per week or ≥ 70% of all recorded days Current ESS score of <10.

Exclusion Criteria:

• Patients with ventilatory failure, Cheyne-Stokes breathing, unstable and untreated coronary or peripheral artery disease, severe and inadequately controlled arterial hypertension, or a history of any sleep-related accident, or who were current professional drivers, were excluded from the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moderate Obstructive Sleep Apnea; Patients whom have an apnea/hypopnea index above fifteen are classified to have moderate obstructive sleep apnea	Device: Withdrawal of Continuous Positive Airway Pressure device; After completing one month of therapeutic management with The Continuous Positive Airway Pressure device and have controlled OSA defined as Apnea Hypopnea Index (AHI) of < 5 while on treatment. At random, a group of participants will cease to use the Continuous Positive Airway Pressure. And they'll have weakly clinic visits where they will fill the Epworth Sleepiness Scale, check their blood pressure, heart rate and undergo Polysomnography for 4 weeks.; Device: Alternation usage of Continuous Positive Airway Pressure Device; After completing one month of therapeutic management with The Continuous Positive Airway Pressure device and have controlled OSA defined as Apnea Hypopnea Index (AHI) of < 5 while on treatment. Randomly, these patients will alternatively use The Continuous Positive Airway Pressure device every other day (e.g. They will use the device 4 days and not use it for 3 days of the week) and they'll have weakly clinic visits where they will fill the Epworth Sleepiness Scale, check their blood pressure, heart rate and undergo Polysomnography for 4 weeks.
Experimental: Severe Obstructive Sleep Apnea; Patients whom have an apnea/hypopnea index with a result higher than thirty are considered to have severe obstructive sleep apnea	Device: Withdrawal of Continuous Positive Airway Pressure device; After completing one month of therapeutic management with The Continuous Positive Airway Pressure device and have controlled OSA defined as Apnea Hypopnea Index (AHI) of < 5 while on treatment. At random, a group of participants will cease to use the Continuous Positive Airway Pressure. And they'll have weakly clinic visits where they will fill the Epworth Sleepiness Scale, check their blood pressure, heart rate and undergo Polysomnography for 4 weeks.; Device: Alternation usage of Continuous Positive Airway Pressure Device; After completing one month of therapeutic management with The Continuous Positive Airway Pressure device and have controlled OSA defined as Apnea Hypopnea Index (AHI) of < 5 while on treatment. Randomly, these patients will alternatively use The Continuous Positive Airway Pressure device every other day (e.g. They will use the device 4 days and not use it for 3 days of the week) and they'll have weakly clinic visits where they will fill the Epworth Sleepiness Scale, check their blood pressure, heart rate and undergo Polysomnography for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achieving a desaturation SPO2 index of >10 or AHI of >5	Achieving a desaturation SPO2 index of >10 or AHI of >5	six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence of excessive sleepiness daytime symptoms	lack of concentration; inability to retain new information; dozing off or feeling sleepy while driving, sitting or talking; fogy mind; feeling sleepy despite long hours of sleeping	six months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary safety endpoint (study stopping rules): The study will be discontinued for any participants if any of the following developed	Symptoms of Obstructive Sleep Apnea Excessive daytime sleepiness Recurrent awakening from sleep Drop in oxygen saturation during sleep that will be measured every 4 nights. Documented AHI of more than 5 in the repeated PSG If the patient developed any acute sickness that required medical attention	six months

Collaborators and Investigators

• Sponsor: King Abdulaziz University

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2020
• Primary Completion (Anticipated): November 30, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: June 29, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 25, 2022

Study Record Updates

• Last Update Posted (Actual): July 25, 2022
• Last Update Submitted That Met QC Criteria: July 20, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: 241-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No