Comparative Outcomes Management With Electronic Data Technology (COMET) Study

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01461473
• Collaborator: (none)
• Enrollment: 131
• Locations: 4
• Arms: 2
• Duration (Months): 30
• Patients Per Site: 32.8
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

STAGE I of the COMET study was to develop an Electronic Network Informatics Infrastructure that prospectively enabled access to and the sharing of clinical and research data.

STAGE II: This was a Comparative Effectiveness Trial (CET) evaluating positive airway pressure (PAP) vs. oral appliance (OA) therapy in improving hypertension and abnormalities in cardiovascular function in overweight/obese patients with obstructive sleep apnea (OSA). Data collected during the STAGE II study was incorporated in Part 3 of the STAGE I study.

STAGE III of the COMET study was completion of data analysis and preparation of the electronic network informatics infrastructure for use beyond the four Clinical Centers to interested CTSA institutions. We also explored expanding ontologies, and the use of federated database methodology.

Condition or Disease	Intervention/Treatment	Phase
Sleep Apnea, Obstructive	Device: Positive Airway Pressure (PAP); Device: Oral Appliance (OA)	N/A

Detailed Description

STAGE I, Part 1: We extracted limited access data sets from an existing research database (prior research patients' data from APPLES research project, where patients consented to provide a limited access data sets to the public domain as required by grants funded by the National Heart, Lung, and Blood Institute [NHLBI], PI: Dr. Clete Kushida) and a dummy database with prepared test data (no real patient data) to evaluate and refine the initial iterations of the informatics infrastructure created via an agile evolutionary development process.

STAGE I, Part 2: We expanded the functionality of the informatics infrastructure by testing its ability to incorporate research data collected from an electronic questionnaire, the Alliance Sleep Questionnaire (ASQ). We enabled data collection using the ASQ in order to use these data to evaluate and refine the iterations for the informatics infrastructure.

STAGE I, Part 3: We expanded the functionality of the informatics infrastructure by testing its ability to incorporate live (ongoing) longitudinal data collected from multiple forms and data sources obtained during the STAGE II study. The addition of these data allowed the COMET Steering Committee to create use cases with a greater diversity of data content. The STAGE II data were used to evaluate and refine the iterations for the expanded informatics infrastructure.

STAGE I, Part 4: Part 4 was designed to expand the collection of data beyond individual research studies, tapping into University-wide systems (e.g., Stride) to link longitudinal data collected during research studies to longitudinal data collected during clinical visits. Only de-identified data were shared with the network, and only the local site held the codebook that translated the Global Identifier (ID) to the Participant ID. All Health Insurance Portability and Accountability Act (HIPAA) regulations were considered.

STAGE II: This stage was comprised of the multicenter, randomized, parallel group, comparative effectiveness trial to compare positive airway pressure (PAP) vs. oral appliance (OA) therapy in improving hypertension and abnormalities in cardiovascular function in overweight/obese patients with obstructive sleep apnea (OSA). Data collected during the STAGE II study were incorporated in Part 3 of the STAGE I study. This comparative effectiveness trial was conducted at 4 clinical centers, and the data collected during this trial were used to test the electronic network informatics infrastructure. The primary aim of the Stage II CET was to evaluate and compare the effect of positive airway pressure and oral appliance therapy on 24-hour blood pressure and vascular structure and function associated with obstructive sleep apnea in a primarily female, overweight/obese hypertensive population.

STAGE III: This stage was comprised of completion of data analysis and preparation of the electronic network informatics infrastructure for deployment beyond the four Clinical Centers to interested Clinical and Translational Science Awards (CTSA) institutions. We also explored expanding the ontologies beyond a sleep-related ontology to other medical ontologies, and the use of federated database methodology.

Study Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: R01: Comparative Outcomes Management With Electronic Data Technology (COMET) Study
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Positive Airway Pressure Participants randomized to standard clinical Positive Airway Pressure (PAP) treatment for Obstructive Sleep Apnea (OSA).	Device: Positive Airway Pressure (PAP); Participants randomized to the Positive Airway Pressure treatment group received adequate Positive Airway Pressure (PAP) pressure therapy by a PAP titration study and used the device for 6 months.; Other Names: Auto-titrating PAP (APAP), Continuous PAP (CPAP)
Active Comparator: Oral Appliance Subjects randomized to standard Oral Appliance (OA) treatment for Obstructive Sleep Apnea (OSA).	Device: Oral Appliance (OA); Participants randomized to the Oral Appliance treatment group received a dental evaluation to determine the optimal setting for the Oral Appliance (OA), and used the appliance for 6 months.; Other Names: Mandibular Advancement Device

Outcome Measures

Primary Outcome Measures

1. Nocturnal Mean Arterial Blood Pressure (NMAP) at 2 Months [2 months]

   Mean arterial blood pressure during the sleep period as recorded by 24-hour ambulatory blood pressure monitoring after approximately 2 months of treatment

Secondary Outcome Measures

1. Nocturnal Mean Arterial Blood Pressure (NMAP) at 6 Months [6 months]

   Nocturnal mean arterial blood pressure as recorded by 24-hour ambulatory blood pressure monitoring after approximately 6 months of treatment

2. Ratio of Nocturnal Mean Arterial Pressure (NMAP) to Daytime Mean Arterial Pressure at 2 Months [2 months]

   Ratio of NMAP to mean daytime arterial pressure, expressed as a percentage at the 2 month visit for PAP and OA arms. The ratio is calculated by dividing the NMAP by the daytime mean arterial pressure; the result is then multiplied by 100 to obtain a percentage.

3. Ratio of NMAP to Daytime Mean Arterial Pressure at 6 Months [6 months]

   Ratio of NMAP to daytime mean arterial pressure, expressed as a percentage at the 6 month visit for PAP and OA arms. The ratio is calculated by dividing the NMAP by the daytime mean arterial pressure; the result is then multiplied by 100 to obtain a percentage.

4. Mean Absolute Flow-Mediated Vasodilatation of the Brachial Artery by Vascular Ultrasound [6 months]

   Mean absolute flow-mediated vasodilatation (FMD) of the brachial artery (i.e., the mean change in brachial artery diameter [in millimeters] from baseline to the value that is obtained after the cuff deflation) as measured by vascular ultrasound (VU) at the 6-month visit

5. Mean Relative Flow-Mediated Vasodilatation of the Brachial Artery by Vascular Ultrasound [6 months]

   Mean relative flow-mediated vasodilatation (FMD) of the brachial artery (i.e., the mean change in brachial artery diameter from baseline to the value that is obtained after the cuff deflation, divided by the baseline value and multiplied by 100) as measured by vascular ultrasound (VU) at the 6-month visit

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age > 18 years.

• BMI > = 25.0 kg/m^2.

• A diagnosis of obstructive sleep apnea based upon medical history and apnea- hypopnea index > = 10.0 or oxygen desaturation index (ODI; ≥4%) ≥ 10.0 on Diagnostic Polysomnogram.

• Report a history of hypertension (or need for treatment for hypertension) which is currently untreated OR taking medication for the treatment of hypertension.

• Stable medication regimen for 2 months prior to the Baseline Testing Visit. As-needed medications such as those used for allergy, cold, or minor pain symptoms may be used at the discretion of the Clinical Center physician.

Exclusion Criteria:

• Cardiovascular disease which, in the judgment of the investigator, if observed during standard clinical practice would lead the treating physician to make every effort to treat the patient's sleep apnea with positive airway pressure, rather than alternative treatments.

• Clinically significant acute or chronic disease that is not well controlled or could affect ability to complete or comply with study procedures, in the opinion of the Clinical Center physician.

• Respiratory disease requiring supplemental oxygen or medication. Individuals with asthma may be included at the discretion of the Clinical Center physician if disease is well controlled and medications are stable for 2 months.

• History of (within 12 months prior to enrollment), or current diagnosis of, Axis I or Axis II psychiatric disorder (other than obstructive sleep apnea) that in the opinion of the Clinical Center physician would affect ability to complete or comply with study procedures (e.g., schizophrenia and other psychotic disorders).

• History of (within 3 months prior to enrollment), or current diagnosis of narcolepsy, idiopathic hypersomnia, restless legs syndrome, rapid eye movement (REM) behavior disorder, persistent situational insomnia, or sleep-related breathing disorders other than obstructive sleep apnea.

• Periodic limb movement arousal index > 10.0 on the Diagnostic Polysomnogram.

• Significant daytime sleepiness at study entry as indicated by:

• an Epworth Sleepiness Scale total score > 16, or a score of 3 (high chance) on the question about risk of dozing "In a car, while stopped for a few minutes in traffic" or

• a report of falling asleep at the wheel, a motor vehicle accident, or near-miss accident due to sleepiness in the past 24 months, which in the judgment of the study physician was not attributable to acute sleep loss.

• Oxygen saturation < 80% for > 10% of sleep time during the Diagnostic Polysomnogram, or intervention with positive airway pressure or oxygen for safety purposes during the Diagnostic Polysomnogram.

• Any prior treatment for obstructive sleep apnea with positive airway pressure or oral appliance, or surgical treatment for obstructive sleep apnea in the past year.

• Contraindication for treatment with either positive airway pressure or oral appliance, in the opinion of the Clinical Center physician or dentist, including significant nasal obstruction, insufficient or loose teeth, dentures, advanced periodontal disease, or significant temporomandibular joint pain.

• Pregnancy.

• Difficulty understanding or speaking English, or inability to read and understand informed consent and study procedures.

• Significant vision, hearing, or motor problems that, in the opinion of the Clinical Center physician, would affect ability to complete study procedures.

• A work schedule that does not allow for nighttime sleep on the 3 nights before each study visit.

• Current or planned participation in another research study.

• Metal objects, devices, or implants that are in or on the body (Stanford Clinical Center only).

• Creatinine clearance <30 and creatinine >1.6 (Stanford Clinical Center only).

• Upper arm circumference > 20 inches

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Sleep Medicine Center	Redwood City	California	United States	94063
2	Harvard Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
3	Center for Sleep and Circadian Neurobiology, University of Pennsylvania School of Medicine	Philadelphia	Pennsylvania	United States	19104
4	University of Wisconsin-Madison School of Medicine, Department of Psychiatry	Madison	Wisconsin	United States	53719

Sponsors and Collaborators

• Stanford University

Investigators

• Study Director: Clete A Kushida, MD, PhD, Stanford University
• Principal Investigator: Allan Pack, MD, Center for Sleep, University of Pennsylvania School of Medicine
• Principal Investigator: Susan Redline, MD, Harvard Brigham and Women's Hospital
• Principal Investigator: Ruth Benca, MD, University of Wisconsin-Madison School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

• Nichols DA, DeSalvo S, Miller RA, Jónsson D, Griffin KS, Hyde PR, Walsh JK, Kushida CA. The COMET Sleep Research Platform. EGEMS (Wash DC). 2014 Nov 24;2(1):1059. doi: 10.13063/2327-9214.1059. eCollection 2014.
• Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993 Apr 29;328(17):1230-5.

• Responsible Party: Clete A. Kushida, Principal Investigator, Stanford University
• ClinicalTrials.gov Identifier: NCT01461473
• Other Study ID Numbers: SU-10182011-8536; 1R01HS019738-01
• First Posted: Oct 28, 2011
• Last Update Posted: May 17, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Clete A. Kushida, Principal Investigator, Stanford University: Obstructive Sleep Apnea; Obstructive Sleep Apnea Syndrome; Sleep Apnea Syndrome, Obstructive; Syndrome, Obstructive Sleep Apnea; Syndrome, Sleep Apnea, Obstructive; Syndrome, Upper Airway Resistance, Sleep Apnea; Upper Airway Resistance Sleep Apnea Syndrome
• Additional relevant MeSH terms: Sleep Apnea Syndromes; Sleep Apnea, Obstructive

Study Results

Participant Flow

Arm/Group Title	Positive Airway Pressure	Oral Appliance
Arm/Group Description	Participants randomized to standard clinical Positive Airway Pressure (PAP) treatment for Obstructive Sleep Apnea (OSA). Positive Airway Pressure: Participants who are randomized to the Positive Airway Pressure treatment group will receive adequate Positive Airway Pressure (PAP) pressure setting through standard clinical polysomnography (PSG) study.	Subjects randomized to standard Oral Appliance (OA) treatment for Obstructive Sleep Apnea (OSA). Oral Appliance: Participants who are randomized to the Oral Appliance Treatment Group will receive a dental evaluation to determine the optimal setting for the Oral Appliance (OA) device.
Period Title: Overall Study
STARTED	72	59
COMPLETED	67	55
NOT COMPLETED	5	4

Baseline Characteristics

Arm/Group Title	Positive Airway Pressure	Oral Appliance	Total
Arm/Group Description	Participants randomized to standard clinical Positive Airway Pressure (PAP) treatment for Obstructive Sleep Apnea (OSA). Positive Airway Pressure: Participants who are randomized to the Positive Airway Pressure treatment group will receive adequate Positive Airway Pressure (PAP) pressure setting through standard clinical polysomnography (PSG) study.	Subjects randomized to standard Oral Appliance (OA) treatment for Obstructive Sleep Apnea (OSA). Oral Appliance: Participants who are randomized to the Oral Appliance Treatment Group will receive a dental evaluation to determine the optimal setting for the Oral Appliance (OA) device.	Total of all reporting groups
Overall Participants	72	59	131
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.85 (12.17)	52.61 (9.84)	53.84 (11.20)
Sex: Female, Male (Count of Participants)
Female	20 27.8%	17 28.8%	37 28.2%
Male	52 72.2%	42 71.2%	94 71.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 4.2%	6 10.2%	9 6.9%
Not Hispanic or Latino	69 95.8%	53 89.8%	122 93.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 5.6%	5 8.5%	9 6.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 5.6%	4 6.8%	8 6.1%
White	62 86.1%	49 83.1%	111 84.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 2.8%	1 1.7%	3 2.3%
Region of Enrollment (participants) [Number]
United States	72 100%	59 100%	131 100%

Outcome Measures

1. Primary Outcome

Title	Nocturnal Mean Arterial Blood Pressure (NMAP) at 2 Months
Description	Mean arterial blood pressure during the sleep period as recorded by 24-hour ambulatory blood pressure monitoring after approximately 2 months of treatment
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

31 participants in the Positive Airway Pressure arm and 29 participants in the Oral Appliance arm failed to return for 24-hour ambulatory blood pressure monitoring at the two-months time point, but did return at the six-month time point for blood pressure monitoring at the six-month time point and to complete the study.

Arm/Group Title	Positive Airway Pressure	Oral Appliance
Arm/Group Description	Participants randomized to standard clinical Positive Airway Pressure (PAP) treatment for Obstructive Sleep Apnea (OSA). Positive Airway Pressure: Participants who are randomized to the Positive Airway Pressure treatment group will receive adequate Positive Airway Pressure (PAP) pressure setting through standard clinical polysomnography (PSG) study.	Subjects randomized to standard Oral Appliance (OA) treatment for Obstructive Sleep Apnea (OSA). Oral Appliance: Participants who are randomized to the Oral Appliance Treatment Group will receive a dental evaluation to determine the optimal setting for the Oral Appliance (OA) device.
Measure Participants	36	26
Mean (Standard Deviation) [mmHg]	82.1 (7.79)	84.3 (9.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Positive Airway Pressure, Oral Appliance
	Comments	These data were analyzed using an analysis of covariance via general linear model (GLM). The GLM has an indicator variable for PAP vs. OA plus covariates for baseline apnea-hypopnea index, gender, site and baseline NMAP. The primary hypothesis tested is that the 2-month means differ between study arms, after adjustment for the above covariates. A Wald statistic was constructed for hypothesis testing.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2067
	Comments
	Method	Analysis of covariance (GLM)
	Comments

2. Secondary Outcome

Title	Nocturnal Mean Arterial Blood Pressure (NMAP) at 6 Months
Description	Nocturnal mean arterial blood pressure as recorded by 24-hour ambulatory blood pressure monitoring after approximately 6 months of treatment
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Positive Airway Pressure	Oral Appliance
Arm/Group Description	Participants randomized to standard clinical Positive Airway Pressure (PAP) treatment for Obstructive Sleep Apnea (OSA). Positive Airway Pressure: Participants who are randomized to the Positive Airway Pressure treatment group will receive adequate Positive Airway Pressure (PAP) pressure setting through standard clinical polysomnography (PSG) study.	Subjects randomized to standard Oral Appliance (OA) treatment for Obstructive Sleep Apnea (OSA). Oral Appliance: Participants who are randomized to the Oral Appliance Treatment Group will receive a dental evaluation to determine the optimal setting for the Oral Appliance (OA) device.
Measure Participants	67	55
Mean (Standard Deviation) [mmHg]	83.1 (9.63)	84.7 (9.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Positive Airway Pressure, Oral Appliance
	Comments	Generalized linear mixed model (GLMM) was fit in which the outcome was regressed on an indicator variable for PAP vs. OA, baseline apnea-hypopnea index, gender, site and baseline value of the outcome. A Wald statistic was constructed for hypothesis testing.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3902
	Comments
	Method	GLMM
	Comments

3. Secondary Outcome

Title	Ratio of Nocturnal Mean Arterial Pressure (NMAP) to Daytime Mean Arterial Pressure at 2 Months
Description	Ratio of NMAP to mean daytime arterial pressure, expressed as a percentage at the 2 month visit for PAP and OA arms. The ratio is calculated by dividing the NMAP by the daytime mean arterial pressure; the result is then multiplied by 100 to obtain a percentage.
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

31 participants in the Positive Airway Pressure arm and 29 participants in the Oral Appliance arm failed to return for 24-hour ambulatory blood pressure monitoring at the two-months time point, but did return at the six-month time point for blood pressure monitoring at the six-month time point and to complete the study.

Arm/Group Title	Positive Airway Pressure	Oral Appliance
Arm/Group Description	Participants randomized to standard clinical Positive Airway Pressure (PAP) treatment for Obstructive Sleep Apnea (OSA). Positive Airway Pressure: Participants who are randomized to the Positive Airway Pressure treatment group will receive adequate Positive Airway Pressure (PAP) pressure setting through standard clinical polysomnography (PSG) study.	Subjects randomized to standard Oral Appliance (OA) treatment for Obstructive Sleep Apnea (OSA). Oral Appliance: Participants who are randomized to the Oral Appliance Treatment Group will receive a dental evaluation to determine the optimal setting for the Oral Appliance (OA) device.
Measure Participants	36	26
Mean (Standard Deviation) [percentage of NMAP to daytime MAP]	86.8 (7.07)	87.0 (7.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Positive Airway Pressure, Oral Appliance
	Comments	A GLMM was fit in which the outcome was regressed on an indicator variable for PAP vs. OA, baseline apnea-hypopnea index, gender, site and baseline value of the outcome. A Wald statistic was constructed for hypothesis testing.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9319
	Comments
	Method	GLMM
	Comments

4. Secondary Outcome

Title	Ratio of NMAP to Daytime Mean Arterial Pressure at 6 Months
Description	Ratio of NMAP to daytime mean arterial pressure, expressed as a percentage at the 6 month visit for PAP and OA arms. The ratio is calculated by dividing the NMAP by the daytime mean arterial pressure; the result is then multiplied by 100 to obtain a percentage.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Two participants in the PAP arm and 1 participant in the OA arm did not have sufficient daytime MAP data to calculate the ratio of NMAP to daytime MAP at 6 months

Arm/Group Title	Positive Airway Pressure	Oral Appliance
Arm/Group Description	Participants randomized to standard clinical Positive Airway Pressure (PAP) treatment for Obstructive Sleep Apnea (OSA). Positive Airway Pressure: Participants who are randomized to the Positive Airway Pressure treatment group will receive adequate Positive Airway Pressure (PAP) pressure setting through standard clinical polysomnography (PSG) study.	Subjects randomized to standard Oral Appliance (OA) treatment for Obstructive Sleep Apnea (OSA). Oral Appliance: Participants who are randomized to the Oral Appliance Treatment Group will receive a dental evaluation to determine the optimal setting for the Oral Appliance (OA) device.
Measure Participants	65	54
Mean (Standard Deviation) [percentage of NMAP to daytime MAP]	86.6 (8.18)	87.9 (6.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Positive Airway Pressure, Oral Appliance
	Comments	A GLMM was fit in which the outcome was regressed on an indicator variable for PAP vs. OA, baseline apnea-hypopnea index, gender, site and baseline value of the outcome. A Wald statistic was constructed for hypothesis testing.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3895
	Comments
	Method	GLMM
	Comments

5. Secondary Outcome

Title	Mean Absolute Flow-Mediated Vasodilatation of the Brachial Artery by Vascular Ultrasound
Description	Mean absolute flow-mediated vasodilatation (FMD) of the brachial artery (i.e., the mean change in brachial artery diameter [in millimeters] from baseline to the value that is obtained after the cuff deflation) as measured by vascular ultrasound (VU) at the 6-month visit
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Positive Airway Pressure	Oral Appliance
Arm/Group Description	Participants randomized to standard clinical Positive Airway Pressure (PAP) treatment for Obstructive Sleep Apnea (OSA). Positive Airway Pressure: Participants who are randomized to the Positive Airway Pressure treatment group will receive adequate Positive Airway Pressure (PAP) pressure setting through standard clinical polysomnography (PSG) study.	Subjects randomized to standard Oral Appliance (OA) treatment for Obstructive Sleep Apnea (OSA). Oral Appliance: Participants who are randomized to the Oral Appliance Treatment Group will receive a dental evaluation to determine the optimal setting for the Oral Appliance (OA) device.
Measure Participants	67	55
Mean (Standard Deviation) [mm]	0.009 (0.0165)	0.012 (0.0196)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Positive Airway Pressure, Oral Appliance
	Comments	Using analysis of covariance (robust MM regression), the outcome was regressed on an indicator variable for PAP vs. OA, baseline outcome, baseline apnea-hypopnea index, gender, site, baseline brachial-artery diameter, body mass index, age, and the interaction of gender and study arm. The latter allows for the possibility that treatment effect may differ between males and females. A Wald statistic was constructed for hypothesis testing.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3449
	Comments
	Method	see Comments
	Comments	Analysis of covariance with robust MM regression due to extreme residuals from initial fit showing strong departure from normal distribution.

6. Secondary Outcome

Title	Mean Relative Flow-Mediated Vasodilatation of the Brachial Artery by Vascular Ultrasound
Description	Mean relative flow-mediated vasodilatation (FMD) of the brachial artery (i.e., the mean change in brachial artery diameter from baseline to the value that is obtained after the cuff deflation, divided by the baseline value and multiplied by 100) as measured by vascular ultrasound (VU) at the 6-month visit
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Positive Airway Pressure	Oral Appliance
Arm/Group Description	Participants randomized to standard clinical Positive Airway Pressure (PAP) treatment for Obstructive Sleep Apnea (OSA). Positive Airway Pressure: Participants who are randomized to the Positive Airway Pressure treatment group will receive adequate Positive Airway Pressure (PAP) pressure setting through standard clinical polysomnography (PSG) study.	Subjects randomized to standard Oral Appliance (OA) treatment for Obstructive Sleep Apnea (OSA). Oral Appliance: Participants who are randomized to the Oral Appliance Treatment Group will receive a dental evaluation to determine the optimal setting for the Oral Appliance (OA) device.
Measure Participants	67	55
Mean (Standard Deviation) [percent change]	2.63 (4.550)	3.51 (5.637)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Positive Airway Pressure, Oral Appliance
	Comments	Using analysis of covariance (robust MM regression), the outcome was regressed on an indicator variable for PAP vs. OA, baseline outcome, baseline apnea-hypopnea index, gender, site, baseline brachial-artery diameter, body mass index, age, and the interaction of gender and study arm. The latter allows for the possibility that treatment effect may differ between males and females. A Wald statistic was constructed for hypothesis testing.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1531
	Comments
	Method	see Comments
	Comments	Analysis of covariance with robust MM regression due to extreme residuals from initial fit showing strong departure from normal distribution.

Adverse Events

Time Frame	6 months per patient
Adverse Event Reporting Description	Standardized questionnaire at each visit
Arm/Group Title	Positive Airway Pressure		Oral Appliance
Arm/Group Description	Participants randomized to standard clinical Positive Airway Pressure (PAP) treatment for Obstructive Sleep Apnea (OSA). Positive Airway Pressure: Participants who are randomized to the Positive Airway Pressure treatment group will receive adequate Positive Airway Pressure (PAP) pressure setting through standard clinical polysomnography (PSG) study.		Subjects randomized to standard Oral Appliance (OA) treatment for Obstructive Sleep Apnea (OSA). Oral Appliance: Participants who are randomized to the Oral Appliance Treatment Group will receive a dental evaluation to determine the optimal setting for the Oral Appliance (OA) device.
All Cause Mortality
	Positive Airway Pressure		Oral Appliance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Positive Airway Pressure		Oral Appliance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/72 (8.3%)		0/59 (0%)
Cardiac disorders
Non-ST elevated myocardial infarction (NSTEMI)	1/72 (1.4%)		0/59 (0%)
General disorders
Dizziness	1/72 (1.4%)		0/59 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Surgeries for Breast Cancer	1/72 (1.4%)	2	0/59 (0%)	2
Nervous system disorders
Death-Acute Ischemic Stroke-Right Hemispheric Infarct	1/72 (1.4%)		0/59 (0%)
Acute Hemorrhagic Stroke (Intraventricular Hemorrhage)	1/72 (1.4%)		0/59 (0%)
Reproductive system and breast disorders
Hyserectomy	1/72 (1.4%)		0/59 (0%)
Other (Not Including Serious) Adverse Events
	Positive Airway Pressure		Oral Appliance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/72 (36.1%)		35/59 (59.3%)
Blood and lymphatic system disorders
Hemodialysis catheter dislodgement	0/72 (0%)		1/59 (1.7%)
Cardiac disorders
Cardiac Arrhythmia	0/72 (0%)		2/59 (3.4%)
Increased High Blood Pressure	4/72 (5.6%)		0/59 (0%)
Ear and labyrinth disorders
Ear Infection	0/72 (0%)		1/59 (1.7%)
Eye disorders
Cataract Surgery	1/72 (1.4%)		0/59 (0%)
Gastrointestinal disorders
Abdominal Pain/Gastroenteritis	4/72 (5.6%)		0/59 (0%)
Esophageal Reflux	1/72 (1.4%)		0/59 (0%)
Constipation	1/72 (1.4%)		0/59 (0%)
General disorders
Motor Vehicle Accident	1/72 (1.4%)		1/59 (1.7%)
Infections and infestations
Sinusitis	1/72 (1.4%)		2/59 (3.4%)
Upper Respiratory Infection/Discomfort	3/72 (4.2%)		10/59 (16.9%)
Tooth Extraction	0/72 (0%)		1/59 (1.7%)
Urinary Tract Infection	1/72 (1.4%)		0/59 (0%)
Injury, poisoning and procedural complications
Fall	1/72 (1.4%)		0/59 (0%)
Musculoskeletal and connective tissue disorders
Injury/Pain in Extremities	3/72 (4.2%)		8/59 (13.6%)
Tooth/Jaw Pain	0/72 (0%)		4/59 (6.8%)
Nervous system disorders
Headache/Migraine	1/72 (1.4%)		1/59 (1.7%)
Spondylosis/Back Pain	0/72 (0%)		3/59 (5.1%)
Psychiatric disorders
Worsened Depression	2/72 (2.8%)		0/59 (0%)
Skin and subcutaneous tissue disorders
Benign Skin Cyst Removal	0/72 (0%)		1/59 (1.7%)
Basal Cell Carcinoma Surgery	1/72 (1.4%)		0/59 (0%)
Nasal Skin Irritation	1/72 (1.4%)		0/59 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.