| Registry | NCT03033901, acronym C-SAS |
|---|---|
| Status | Completed |
| Study type | Observational |
| Enrollment | 345 (Actual) |
| Sponsor | James A. Haley Veterans Administration Hospital (Fed); collaborators: Patient-Centered Outcomes Research Institute, Craig Hospital, Moss Rehabilitation Research Institute, University of Washington, Baylor Institute for Rehabilitation, Ohio State University, University of South Florida, Palo Alto Veterans Institute for Research, North Florida Foundation for Research and Education |
| Conditions | Apnea, Sleep, Brain Injury, Traumatic |
| Interventions | Polysomnography - Level 1 and Level 3, Actigraphy monitoring, Sleep Apnea Screening (Device, other) |
| Dates | start 2017-05-01, primary completion 2020-02-01, completion 2020-02-01, first posted 2017-01-27, last updated 2023-03-29 |
| Locations | 6 sites in United States |
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All trials for Apnea, Sleep All trials for Brain Injury, Traumatic All trials of Polysomnography - Level 1 and Level 3 All trials of Actigraphy monitoring
Background: Sleep disorders, including sleep apnea, are common after traumatic brain injury and affect recovery and negatively influence participation in rehabilitation. Sleep apnea is a breathing problem while persons sleep and causes further brain damage and problems with thinking, daily functioning, and overall health. Earlier diagnosis and treatment is important for traumatic brain injury (TBI) survivors to maximize the recovery process. There is little information that guides TBI doctors on how to identify sleep apnea during inpatient TBI rehabilitation, a phase in which people experience the potential for a rapid pace of improvement. The Agency for Healthcare Research has highlighted gaps in best methods for identifying sleep apnea and separately in helping consumers with TBI rehabilitation choices. Partnering with survivors, caregivers, and administrators, investigators developed this study to compare sleep apnea screening and diagnostic tools in TBI rehabilitation settings. This information will provide clinicians, providers, and patients with the best information for early identification of sleep apnea to remove negative influence on the pace of recovery in early phases after TBI.
The Goal: Investigators will compare existing screening (Aim 1) and diagnostic tools (Aim 2) in TBI patients undergoing inpatient rehabilitation. For the second aim, investigators will determine if a more accessible diagnostic test is sufficient to diagnose sleep apnea compared to the traditional method used which is less accessible to consumers. If the more accessible test is good enough, this will increase recognition of this problem and increase patient access to earlier sleep apnea treatment.
Stakeholders and Products. TBI survivors, caregivers, researchers, and policymakers working together on this study helped develop the study questions. Idea exchanges included ways to reach clinicians and TBI survivors/caregivers via existing educational programming and online tools for consumers such as fact sheets and patient/caregiver-focused videos. Other traditional methods will include targeting professional magazines, conferences, and research journals that reach professionals working with TBI survivors and their families at the time of admission to rehabilitation and during the recovery process. This study will occur at rehabilitation hospitals around the country who enroll TBI survivors into a lifetime study called the TBI Model System funded by the Department of Health and Human Services and Veterans Affairs (VA).
Background and Significance:
Meta-analyses of TBI studies found prevalence of obstructive sleep apnea (OSA) was 12 times higher than community-based studies. Yet, sleep apnea in those with TBI is largely undiagnosed. Given that sleep is critical for neural repair and disordered sleep may play a role in slowing functional recovery and prolonging rehabilitation, early detection of sleep apnea is critical (Stakeholder Input). Minimal guidance exists informing TBI and sleep medicine physicians regarding assessment of sleep disorders in the acute rehabilitation setting. The Agency for Healthcare Research and Quality's (AHRQ) Comparative Effectiveness Review highlighted insufficient comparative effectiveness evidence for diagnostic and screening tools. This study proposes to leverage the existing TBI Model System research consortium (TBIMS), funded by the Departments of Health and Human Services and Veterans Affairs, to improve early detection of sleep apnea in patients with TBI undergoing inpatient rehabilitation at six study sites. Study aims are focused around components of phased testing for sleep apnea. Findings will inform clinician's decisions for screening and diagnostic tests to facilitate earlier recognition of sleep apnea (outcome) and subsequently prescribe appropriate treatments.
Study Aims:
Aim I: (Screening) For individuals with TBI, determine comparative effectiveness of 2 American Academy of Sleep Medicine (AASM) endorsed screening tools (STOPBang Questionnaire \[STOPBang\] vs. Actigraphy \[ACG\]) to identify those at high risk of sleep apnea as diagnosed through Level 1 polysomnography (PSG). Long-term Objectives: To inform clinician's choices for screening measures to determine presence of sleep apnea.
Exploratory Aim:
Evaluate alternative screening tools (Berlin Questionnaire, Multivariate Apnea Prediction Index \[MAPI\]) to Level 1 PSG in Aim 1.
Aim II: (Diagnosis) This study will determine the diagnostic accuracy (non-inferiority) of Level 3 PSG in determining presence of sleep apnea in patients with acute TBI patients in the rehabilitation setting. Level 1 PSG will be used as the criterion standard. Long-term Objectives: To inform clinician's choices of diagnostic tests to determine presence of sleep apnea and prescribe appropriate treatments. If Level 3 portable PSG is equivalent to the less accessible Level 1 PSG, this will increase consumer accessibility.
Study Design:
This is a 3-year, multi-center prospective observational cohort study.
Intervention and Comparators:
In Aim I, the screening tools STOPBang and ACG will be compared against one another to determine their sensitivity and specificity in identifying patients with TBI at risk for sleep apnea. In Aim II, the non-inferiority of Level 3 PSG in determining presence and severity of sleep apnea in patients with moderate to severe TBI will be compared to Level 1 PSG.
Study Population:
Consecutive participants to neurorehabilitation at an existing National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) or VA funded TBIMS Center will make up the study population. Patients will be age 16 and older (18 or older at VA sites), with moderate to severe TBI, admitted for rehabilitation in a U.S. TBIMS inpatient rehabilitation facility, and sleeping > 2 hours/night suggesting habitual sleep duration. Based on historical data from the six study sites participating in this study, investigators in this study conservatively estimated that 70% of patients admitted for inpatient TBI rehabilitation would consent into this study (N=20/month), resulting in a 13-month enrollment estimate of 259 patients. Power analyses of each study aim suggest that a sample size of 237 is the largest sample size needed for sufficient power. The sites participating in this study aim to collectively enroll 259 patients to account for possible further attrition. Based on TBIMS data acquired over the past 25-years, 44% of the sample is female, 64% are categorized as Non-White, median age is 38 years, with predominantly moderate to severe TBI.
Primary outcomes consist of:
1\) Positive predictive power of screening tools: STOPBang and ACG, 2) Equivalency in detection of sleep apnea via Level 1 and Level 3 PSG, with diagnosis of sleep apnea based on overall apnea-hypopnea index (AHI) > 5.
Analytic Methods:
Aim 1: Investigators expect that STOPBang values > 5 and abnormal ACG total sleep time (< 5 hours with desaturation) will produce sufficiently high SEs with reasonable tradeoff in SP (noting that SE and SP are inversely related). Similarly, for Level 1 PSG, a diagnosis of sleep apnea will be made if AHI ≥ 5. Cross-tabulations of STOPBang and ACG screening for high risk of sleep apnea (positive/negative) versus Level 1 PSG diagnosis (positive/negative) will be constructed and estimates of diagnostic accuracy (i.e., sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy) will be estimated along with 95% confidence intervals. To address hypothesis 1.1, two-sided McNemar's tests will be used to compare the paired SEs and paired SPs between STOPBang and ACG assuming a significance level of α = 0.05.
Aim 2: The sensitivity (SE) and specificity (SP) of Level 3 PSG (compared to Level 1 PSG, the reference gold standard) will each be estimated and compared to fixed hypothesized rates of SE and SP of 90% and 60%, respectively, considered sufficiently large enough. Level 1 PSG (reference) diagnosis of sleep apnea will be made based on AHI ≥ 5. Level 3 PSG (test) diagnosis will be made based AHI ≥ 5. A cross-tabulation of Level 3 PSG (positive/negative) versus Level 1 PSG (positive/negative) will be constructed and standard measures of diagnostic accuracy will be estimated along with 95% confidence intervals (i.e., sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy).To test for non-inferiority of the SE to 90% and the SP to 60%, a non-inferiority threshold of 0.1 is assumed. If the lower bound on the 95% confidence interval for SE is strictly above 80% and the lower bound on the confidence interval for SP is strictly above 50% then non-inferiority of Level 3 PSG (compared to Level 3 PSG) can be established.
Sex: All, ages: 16 Years to any
Inclusion Criteria: 1. Meet case definition for TBI: (A). VA (for James A. Haley Veterans' Hospital): i. Persons fitting the definition of traumatic brain injury (TBI), defined as a traumatically induced structural brain injury, brain trauma, or damage to brain tissue, and/or physiological disruption of brain function as a result of an external mechanical force (also including acceleration/deceleration movement without direct external trauma to the head, a foreign body penetrating the brain, forces generated from events such as a blast or explosion, or other force) as evidenced by self-reported or medically documented (physical examination or mental status examination) new onset or worsening of at least one of the following clinical signs immediately following the event: (a) a period of loss of or a decreased level of consciousness; (b) alteration in mental state at the time of the injury (confusion, disorientation, slowed thinking); (c) loss of memory for events immediately before or after the injury; (d) posttraumatic amnesia (PTA); (d)neurological deficits (weakness, imbalance, change in vision, praxis, paresis/plegia, sensory loss, aphasia, etc.) that may or may not be transient; or (e) intracranial lesion. ii. Age 18 or older at the time of index TBI. iii. Admitted to one of the five designated VA Polytrauma Rehabilitation Centers (PRCs) for comprehensive rehabilitation with the presenting diagnoses of TBI. Comprehensive rehabilitation must occur in the PRC and meet the following criteria: (a) Medical and rehabilitation care are supervised on a regular basis by a physician affiliated with the PRC; (b) 24-hour nursing care is provided to the patient; (c) Physical Therapy (PT), Occupational Therapy (OT), Speech, Rehabilitation Psychology, Neuropsychology, and/or family support/education are provided in an integrated team approach with the expectation of further gain; (d) Operates in a manner consistent with Commission on Accreditation of Rehabilitation Facilities (CARF) standards for brain injury inpatient rehabilitation and/or Medicare requirements for inpatient rehabilitation. OR (B). Civilian (for civilian sites): Damage to brain tissue caused by an external mechanical force, alteration of consciousness > 24 hours, or loss of consciousness >30 minutes, or Glasgow Coma Scale (GCS) score in the Emergency Department of3-12, or intracranial abnormalities on imaging regardless of GCS; AND 2. admission to an inpatient brain injury rehabilitation program; 3. minimum age 16 years at civilian sites and 18 years at the VA site; 4. Understands and provides informed consent to participate (or, if unable, healthcare proxy / legal guardian understands and provides informed consent for the patient); 5. sleep duration > 2 hours/night. Although not specifically targeted, pregnant women and people with intellectual developmental disorders or prior psychiatric histories meeting the above inclusion/exclusion criteria can be enrolled in this study. Individuals with known history of sleep apnea will be eligible for the study and apnea status will be reconfirmed with new diagnostic study. Exclusion Criteria: 1. persons less than 16 years old at civilian sites and less than 18 years old at VA site will not be included; 2. pre-injury diagnosis of narcolepsy or persistent daytime somnolence as documented in patient's medical record and/or family report; and/or 3. tracheostomy placed and decannulation or overnight capping of the tracheostomy not feasible during rehabilitation hospitalization.
| Milestone | Single Group |
|---|---|
| Started | 345 |
| Completed | 248 |
| Not completed | 97 |
Time frame: Adverse events time frame was between May 1, 2017 (starting enrollment) until February 1, 2020 (end of study). For each participant, adverse events monitoring occurred between time of study enrollment and either (1) time completed all study procedures, or (2) time participant withdrew from study. The adverse event monitoring period lasted for 2 years and 9 months. For the study sample as a whole, the average monitoring period was 8 days.
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|---|---|---|
| Single Group | 0/248 (0.0%) | 0/248 (0.0%) | 0/248 (0.0%) |
Limitations and caveats: The sample may not represent the full population of inpatient rehabilitation patients with TBI; Short lengths of stay impacted study participation; unclear if findings extend to chronic phases of TBI.
| Facility | City | Country | Status |
|---|---|---|---|
| Craig Hospital | Englewood, Colorado | United States | |
| James A. Haley Veterans' Hospital | Tampa, Florida | United States | |
| The Ohio State University | Columbus, Ohio | United States | |
| Albert Einstein Healthcare Network/Moss Rehabilitation Hospital | Elkins Park, Pennsylvania | United States | |
| Baylor Institute for Rehabilitation | Dallas, Texas | United States | |
| University of Washington | Seattle, Washington | United States |