A five-year, nearly $14 million award from the Patient-Centered Outcomes Research Institute, or PCORI, will support a University of Arizona-led clinical trial comparing three common treatments for obstructive sleep apnea, a potentially serious condition that affects about 12% of the U.S. population.

Obstructive sleep apnea occurs when the airway repeatedly collapses during sleep, disrupting breathing. The condition increases the risk of excessive daytime sleepiness, high blood pressure and cardiovascular disease. U of A sleep researchers will compare the benefits and drawbacks of the treatments to better understand which works best for which patients.

"Sleep apnea can significantly affect quality of life and is costly to the workforce through lost productivity," said Dr. Sairam Parthasarathy, director of the Center for Sleep, Circadian & Neuroscience Research and professor of medicine in the College of Medicine – Tucson. "Each of the three available therapies has benefits and downsides. Our goal is to understand which treatment works best for an individual patient."

Parthasarathy will lead the clinical trial. He and his team have previously received PCORI funding to study CPAP, or continuous positive airway pressure, adherence and other strategies to improve sleep apnea treatment. PCORI is a nonprofit organization with a mission to fund patient-centered comparative clinical effectiveness research designed to provide patients and those who care for them with evidence to make better-informed health care decisions.

An estimated 47 million people in the U.S. have some form of sleep apnea, and about 10 to 12 million use CPAP therapy. This study is comparing the effectiveness of three sleep apnea therapies head-to-head in patients receiving care at sleep clinics.

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The three treatments include CPAP, which delivers pressurized air through a mask worn during sleep; a dental device designed to keep the airway open; and an oral medication combining atomoxetine and oxybutynin. Each treatment option has potential side effects. CPAP may cause mask-related skin irritation and gas and bloating. Dental devices can result in jaw pain and discomfort. The pill therapy may contribute to insomnia and urinary retention in some individuals.

The study will assess treatment effectiveness using multiple measures, including daytime sleepiness, blood pressure, treatment adherence, adverse effects and patient-reported quality of life.

Researchers also will evaluate changes in the apnea-hypopnea index, a standard measure used to diagnose sleep apnea and determine its severity. The index reflects the number of breathing pauses or partial reductions that occur per hour of sleep.

"Our ultimate measure is health and quality of life, as reported by patients themselves," Parthasarathy said.

Researchers plan to enroll 2,400 people with obstructive sleep apnea and follow them for 12 months. Participants will be recruited with the help of a patient advocacy group to ensure a diverse study population. The primary study site will be the U of A in Tucson, with additional sites at the University of Miami, the University of Maryland and Stanford Medicine.

The findings are intended to help both patients and clinicians make more informed, cost-effective treatment decisions.

"Who responds best to which treatment? Are certain therapies more effective for specific types of sleep apnea, health conditions, or for men versus women?" Parthasarathy said. "Those are the kinds of questions we aim to answer."

Adherence to treatment schedules remains a challenge, particularly with CPAP therapy. Recent clinical studies have shown that patients who do not follow CPAP instructions face a higher risk of heart-related complications.

Stakeholder input will play a key role in designing the trial. Parthasarathy's team will engage physicians, patients, insurers – including Medicare representatives – healthcare systems and policymakers.

"Engaging stakeholders helps ensure the study addresses real-world decision-making. The results have the potential to influence how patients and physicians choose treatments," Parthasarathy said. "Our goal is not to declare one therapy superior to the others. We want to match the right treatment to the right patient so people and their physicians can make informed decisions."

The three additional clinical trial site principal investigators include Dr. Clete Kushida, chief of the Stanford Division of Sleep Medicine and medical director of the Stanford Sleep Medicine Center, Stanford Medicine;  Emerson Wickwire, professor and section chief of sleep medicine at the University of Maryland School of Medicine; and Girardin Jean-Louis, professor of neurology, psychology, and public health and director of the Center for Translational Sleep and Circadian Sciences at the University of Miami Miller School of Medicine.

Parthasarathy acknowledged the importance – and necessity – of a collaborative effort in such a large clinical trial.

"It is tremendously valuable to bring together the complementary expertise and deep scientific knowledge of site principal investigators from leading institutions to guide a multi-center randomized clinical trial in a critical area of sleep science," he said. "Their collective leadership enhances methodological rigor, strengthens cross-site collaboration and ensures that the study addresses clinically meaningful questions with broad impact on patient care and the advancement of sleep medicine."