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

Study Overview
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Brief Summary
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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: NO CPAP (NOCPAP Group): Who will stop using the CPAP device. 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.

Detailed Description
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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.

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

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Device: Withdrawal of Continuous Positive Airway Pressure device
* Device: Alternation usage of Continuous Positive Airway Pressure Device


Participation Criteria
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Eligibility Criteria
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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

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moderate Obstructive Sleep Apnea<br>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<br>* 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.<br>Device: Alternation usage of Continuous Positive Airway Pressure Device<br>* 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.<br>|
| Experimental: Severe Obstructive Sleep Apnea<br>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<br>* 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.<br>Device: Alternation usage of Continuous Positive Airway Pressure Device<br>* 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.<br>|

What is the study measuring?
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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 |