The Combination of Aroxybutynin and Atomoxetine in the Treatment of Obstructive Sleep Apnea (MARIPOSA): A Randomized Controlled Trial.

Rationale: Obstructive sleep apnea (OSA) is a common sleep disorder for which the principal treatment option, continuous positive airway pressure, is often poorly tolerated. There is currently no approved pharmacotherapy for OSA. However, recent studies have demonstrated improvement in OSA with combined antimuscarinic and noradrenergic drugs. Objectives: The aim of this study was to evaluate the efficacy and safety of AD109, a combination of the novel antimuscarinic agent aroxybutynin and the norepinephrine reuptake inhibitor atomoxetine, in the treatment of OSA. Methods: Phase II randomized, double-blind, placebo-controlled, parallel-group, 4-week trial comparing AD109 2.5/75 mg, AD109 5/75 mg, atomoxetine 75 mg alone, and placebo (www.clinicaltrials.gov identifier NCT05071612). Measurements and Main Results: Of 211 randomized patients, 181 were included in the prespecified efficacy analyses. Sleep was assessed by two baseline and two treatment polysomnograms. Apnea-hypopnea index with a 4% desaturation criterion (primary outcome) was reduced from a median (IQR) of 20.5 (12.3-27.2) to 10.8 (5.6-18.5) in the AD109 2.5/75 mg arm (-47.1%), from 19.4 (13.7-26.4) to 9.5 (6.1-19.3) in the AD109 5/75 mg arm (-42.9%; both P < 0.0001 vs. placebo), and from 19.0 (11.8-28.8) to 11.8 (5.5-21.5) with atomoxetine alone (-38.8%; P < 0.01 vs. placebo). Apnea-hypopnea index with a 4% desaturation criterion decreased from 20.1 (11.9-25.9) to 16.3 (11.1-28.9) in the placebo arm. Subjectively, there was improvement in fatigue with AD109 2.5/75 mg (P < 0.05 vs. placebo and atomoxetine). Atomoxetine taken alone decreased total sleep time (P < 0.05 vs. AD109 and placebo). The most common adverse events were dry mouth, insomnia, and urinary hesitancy. Conclusions: AD109 showed clinically meaningful improvement in OSA, suggesting that further development of the compound is warranted. Clinical trial registered with www.clinicaltrials.gov (NCT05071612).

Oral appliance therapy and hypoglossal nerve stimulation as non-positive airway pressure treatment alternatives for obstructive sleep apnea: a narrative expert review.

This perspective on alternatives to positive airway pressure (PAP) therapy for the treatment of obstructive sleep apnea (OSA) summarizes the proceedings of a focus group that was conducted by the Sleep Research Society Foundation. This perspective is from a multidisciplinary panel of experts from sleep medicine, dental sleep medicine, and otolaryngology that aims to identify the current role of oral appliance therapy and hypoglossal nerve stimulation for the treatment of OSA with emphasis on the US practice arena. A secondary aim is to identify-from an implementation science standpoint-the various barriers and facilitators for adoption of non-PAP treatment that includes access to care, multidisciplinary expertise, reimbursement, regulatory aspects, current treatment guidelines, health policies, and other factors related to the delivery of care. The panel has contextualized the review with recent events-such as a large-scale PAP device recall compounded by supply chain woes of the pandemic-and emerging science in the field of OSA and offers solutions for multidisciplinary approaches while identifying knowledge gaps and future research opportunities.

Pulse oximetry saturation patterns detect repetitive reductions in airflow.

OBJECTIVE: Postoperative patients exhibiting signs or symptoms of obstructive sleep apnea (OSA) have been identified to be at increased risk for respiratory compromise. One of the key markers associated with OSA is repetitive reductions in airflow (RRiA). A real-time pulse oximeter saturation pattern recognition algorithm (OxiMax SPD™ intended for adult in-hospital use only) designed to detect specific signatures in the SpO(2) trend associated with RRiA may provide caregivers early indication of its presence so they can treat the patient appropriately. The purpose of our study was to test the performance of saturation pattern detection (SPD) in a clinical study targeting subjects with a high prevalence of RRiA. METHODS: Overnight polysomnograph (PSG) recordings were collected on 104 sleep lab patients. RRiA was defined in terms of specific criteria from four PSG signals, evaluated in consecutive 10 min epochs. PSG scoring was conducted blind to calculation of SPD. Statistical measures of sensitivity, specificity and area under the receiver operating characteristic (ROC) curve were calculated for the detection of RRiA by SPD. RESULTS: Data were analyzed for 92 valid sets of patient recordings, encompassing 3,917 epochs. At the highest available SPD alert setting, the sensitivity was 80.2% (95% C.I. = 76.8-83.3%), the specificity was 88.3% (87.2-89.3). Area under the ROC curve was 0.87 (0.84-0.89). CONCLUSIONS: The real-time SPD algorithm was able to detect episodes of RRiA in sleep lab patients with a high degree of sensitivity and specificity.

A pilot study assessing adherence to auto-bilevel following a poor initial encounter with CPAP.

STUDY OBJECTIVES: We hypothesized that early intervention with an auto bilevel device would improve treatment adherence compared to CPAP among OSA patients with a poor initial experience with lab-based CPAP titration. METHODS: Patients with a poor initial CPAP experience were recruited for this parallel group, randomized, double-blind, controlled pilot study. After an in-lab titration, patients were randomized with either an auto-bilevel device or CPAP. Treatment adherence and functioning were assessed at 90 days. RESULTS: We enrolled 51 subjects, with 47 completing the protocol. Groups were equally matched for gender, age, education, and OSA severity. There was no significant difference in the proportion of compliant subjects (≥ 4 h/night) between the auto bilevel and CPAP groups (62% vs. 54%; p = 0.624) after 90 days of use. Functional outcomes significantly improved in both groups during treatment use (p < 0.001) but did not differ between groups. CONCLUSIONS: There was no statistically significant difference in adherence between the auto bilevel and CPAP groups in this study. Patients with a poor initial CPAP exposure may still achieve an acceptable long-term clinical outcome. Both groups demonstrated comparably significant improvements in functional outcomes, sleepiness, and fatigue complaints over the treatment period. CLINICAL TRIALS INFORMATION: NCT00635206 ClinicalTrials.gov

Obstructive sleep apnea devices for out-of-center (OOC) testing: technology evaluation.

Guidance is needed to help clinicians decide which out-of-center (OOC) testing devices are appropriate for diagnosing obstructive sleep apnea (OSA). A new classification system that details the type of signals measured by these devices is presented. This proposed system categorizes OOC devices based on measurements of Sleep, Cardiovascular, Oximetry, Position, Effort, and Respiratory (SCOPER) parameters.Criteria for evaluating the devices are also presented, which were generated from chosen pre-test and post-test probabilities. These criteria state that in patients with a high pretest probability of having OSA, the OOC testing device has a positive likelihood ratio (LR+) of 5 or greater coinciding with an in-lab-polysomnography (PSG)-generated apnea hypopnea index (AHI) ≥ 5, and an adequate sensitivity (at least 0.825).Since oximetry is a mandatory signal for scoring AHI using PSG, devices that do not incorporate oximetry were excluded. English peer-reviewed literature on FDA-approved devices utilizing more than 1 signal was reviewed according to the above criteria for 6 questions. These questions specifically addressed the adequacy of different respiratory and effort sensors and combinations thereof to diagnose OSA. In summary, the literature is currently inadequate to state with confidence that a thermistor alone without any effort sensor is adequate to diagnose OSA; if a thermal sensing device is used as the only measure of respiration, 2 effort belts are required as part of the montage and piezoelectric belts are acceptable in this context; nasal pressure can be an adequate measurement of respiration with no effort measure with the caveat that this may be device specific; nasal pressure may be used in combination with either 2 piezoelectric or respiratory inductance plethysmographic (RIP) belts (but not 1 piezoelectric belt); and there is insufficient evidence to state that both nasal pressure and thermistor are required to adequately diagnose OSA. With respect to alternative devices for diagnosing OSA, the data indicate that peripheral arterial tonometry (PAT) devices are adequate for the proposed use; the device based on cardiac signals shows promise, but more study is required as it has not been tested in the home setting; for the device based on end-tidal CO(2) (ETCO(2)), it appears to be adequate for a hospital population; and for devices utilizing acoustic signals, the data are insufficient to determine whether the use of acoustic signals with other signals as a substitute for airflow is adequate to diagnose OSA.Standardized research is needed on OOC devices that report LR+ at the appropriate AHI (≥ 5) and scored according to the recommended definitions, while using appropriate research reporting and methodology to minimize bias.