Auto Bilevel Adherence Following a Poor Initial Encounter With Continuous Positive Airway Pressure (CPAP)

Phase IV Study of Bi-Level Positive Positive Airway Pressure (BiPAP)Compared to Nasal Continuous Positive Airway Pressure (CPAP) Therapy

The primary objective outcome is the proportion of participants compliant (at least four hours of use per night for all nights) in the Auto Bilevel group compared to the continuous positive airway pressure (CPAP) group after 90 days of treatment during the investigation. Proportion will be calculated using the cumulative number of hours on therapy divided by the total number of days of the investigation for each participant. The mean and standard deviation of these mean therapy hours will then be calculated for each arm of the investigation. Participants with compliance of at least four hours will be classified as "compliant" and those with less than four hours will be classified as "non-compliant". The null hypothesis will be rejected if the mean of the primary objective outcome for all participants in the BiPAP® Auto with Bi-Flex® therapy (auto Bilevel) arm is significantly greater than that for all participants in the CPAP therapy arm

Initial Screening

It is preferred that participant's are recruited the morning after their failed clinical CPAP titration in the lab. Participants are able to be enrolled within ninety days following this failure if circumstances preclude approach and consent the morning after titration failure. Participants will be asked to wear the Actiwatch for approximately seven days prior to the clinical titration polysomnogram (PSG; and again for seven days prior to their final visit .) Actiwatch is worn on the participant's wrist to assess sleep continuity. Participants will be asked to press the "Marker button" on the Actiwatch when they get in bed each night to have a documented time mark when the device is downloaded. Participants will also be asked to fill in the sleep diary (provided by sleep clinic) during the seven days (14 days total; 7 at the beginning of the study and 7 days prior to the 90 Day visit) they use the Actiwatch.

Randomization/Therapy Initiated (Visit #1)

Participants will be randomized and scheduled for a BiPAP® Auto with Bi-Flex® titration or CPAP titration night in the lab. General therapy titration guidelines are documented in Appendix I & II (see Appendix I & II at end of document). Heart Rate Variability (HRV) will be assessed at both the diagnostic portion and titration portion of the research PSG. During the diagnostic portion of the research PSG, HRV needs to be assessed for ten minutes while the participant is awake. At the end of the titration portion of the research PSG, the HRV needs to be assessed for ten consecutive minutes while the participant is awake.

Enrolled participants will then complete a questionnaire to assess functional outcomes of sleep quality (FOSQ), Epworth Sleepiness Scale (ESS), Visual Analog Scale (VAS) for mask comfort and satisfaction with therapy, Psychomotor Vigilance Task (PVT), attitudes toward use measurement, and Fatigue Severity Scale (FSS; see Appendix III for description of measurements).

Participants will be set up with their respective machines after titration or within ten days (10 +/- 2) days of titration and will take these devices home for the next three months. Thus, total participation in the trial will be on average 3-4 months. All positive airway pressure machines will include a programmed SmartCard to monitor objectively compliance. Participants randomized to standard CPAP therapy will receive a SmartCard programmed to provide CPAP at their prescribed pressure. Both the participant and the sleep health staff administering the questionnaires and psychomotor vigilance task, will be blinded to the therapy the SmartCard is programmed to provide. Participants randomized to novel therapy will receive a SmartCard programmed to provide BiPAP® Auto with Bi-Flex®. The SmartCard programming will be done by an unblinded study staff member. The settings for the novel therapy will be:

• Min Expiratory Positive Airway Pressure (EPAP) = 4 cmH2O for prescribed CPAP ≤ 10 cmH2O (use 6 cmH2O for prescribed CPAP > 10 cmH2O)
• Max Inspiratory Positive Airway Pressure (IPAP) = 25 cm H2O
• Min Pressure Support (PS) = 2 cm H2O (cannot be adjusted)
• MaxPS = 8 cm H2O
• Bi-Flex setting of 3

The SmartCard is inserted into the device to provide the programmed therapy. Both the participant and CPAP therapist will be blinded to the therapy the SmartCard is programmed to provide. The other supplies necessary to use the therapy at home will also be provided to the participant (i.e. mask, tubing, humidifier, etc.).

The CPAP therapist will also provide the training necessary to use the device at home and provide a number to call in case the participant encounters any difficulty using the device at home.

Standardized Counseling to Optimize Adherence to Therapy

Counseling to optimize adherence to CPAP therapy will consist of:

1. The clinician will discuss complaints regarding CPAP therapy to identify potential contributors to poor adherence to therapy. The standardized counseling to optimize adherence includes the following measures to address patient complaints and concerns:

   Interface

   • Assure current mask is properly applied and headgear is properly adjusted.
   • Persistent mask leaks or mask discomfort, skin trauma, or skin irritation will be addressed first by verifying mask and headgear adjustment and mask sizing. An alternate mask can be used if the problems cannot be addressed by fit or adjustment interventions.
   • If mouth leaks are the primary concern and a nasal mask is being used, then a nasal/oral mask will be considered or a chin strap will be offered in combination with nasal mask use.

   Therapy Side Effects

   • All patients will have initially been placed on a CPAP device with heated humidification. For continued oro-pharyngeal dryness, nasal dryness, nasal congestion, or rhinitis, humidification will be increased. Saline nasal sprays, steroids, or decongestants can be prescribed, if needed.
   • Dyspnea on CPAP or claustrophobia will be addressed with counseling as needed.
   • Note: Reducing the prescribed pressure to improve adherence will not be considered at this time.

2. A standardized description of obstructive sleep apnea (OSA) and its risks will be reviewed with the participant, as well as the American Academy of Sleep Medicine Fact Sheet Drowsy Driving (see Appendix III).

3. A standardized description of the evidence regarding the benefits of positive pressure therapy to treat OSA will be reviewed with the participant.

Participants will be instructed to use the device as much as possible while they are sleeping and to also make sure they allow an adequate opportunity to sleep each night.

Participants who meet the inclusion/exclusion criterion below and are willing to participate in the protocol when contacted will be enrolled into the study. Participants need to meet all of the following inclusion criterion below:

Inclusion Criterion:

1. Age 21-75
2. New Diagnosis of OSA with a baseline respiratory disturbance index (RDI) ≥ 15 events/hr of sleep determined by either full night or split night PSG
3. Able and willing to provide written informed consent
4. Able to follow study procedures
5. Sub-optimal PSG titration with at least 3 hours of attempted PAP titration (defined below): and deemed by their physician as a titration failure

Sub-optimal PSG titration: at least one of the following:

1. Poor sleep efficiency during titration period (sleep efficiency ≤ 70%) (participants may be on sleep medications as per standard lab CPAP protocol ) or;
2. Frequent arousals based on three seconds of alpha frequency on EEG (non periodic limb movement (PLM)-related) of 20 or greater per hour during the titration portion of the study or;
3. CPAP titration aborted due to participant's request (due to intolerance), or
4. Persistent sleep disruption despite therapeutic CPAP therapy and in the judgment of the reviewing physician, suggesting a low probability to CPAP adherence

Exclusion Criteria:

1. Participation in another interventional research study within the last 30 days
2. Major uncontrolled medical or psychiatric condition such as congestive heart failure, neuromuscular disease, renal failure etc.
3. Prior CPAP or Bi-Level PAP use (within last 2 years)
4. Chronic respiratory failure or insufficiency, moderate Chronic Obstructive Pulmonary Disease (COPD) (FEV1 < 60%), or any known condition of an elevation of arterial carbon dioxide levels while awake
5. Surgery of the upper airway, nose, sinus, or middle ear within the previous 90 days
6. Presence of an untreated, diagnosable, non-OSA related sleep disorder (e.g. restless legs syndrome, insomnia, etc.)
7. Periodic Limb movement arousal index of 10 or greater.
8. Refusal to consider further interventions to standard CPAP to optimize positive pressure therapy (e.g. different mask than what was used in lab)
9. PAP therapy otherwise medically complicated or contraindicated such as those with a difficult to size or adjust interface (mask) resulting in facial pain, skin irritation or trauma, or excessive air leaks
10. Shift workers or people experiencing jet lag
11. Known history of alcohol and or drug abuse
12. Diagnosis of Complex Sleep Apnea, (appears to be classic obstructive or mixed sleep apnea, but exhibits disruptive central apneas and periodic breathing on CPAP) 11, 12 or persistent central apnea during diagnostic PSG.
13. Diagnosis of Attention Deficit Hyperactivity Disorder
14. Chronic Hypnotic use (nightly use for three months or less)