| Autor: |
Dauvilliers Y; National Reference Center for Narcolepsy, Sleep and Wake Unit, Department of Neurology, Gui-de-Chauliac Hospital, Montpellier University Hospital, Montpellier, France.; INSERM U1061, Montpellier University, Montpellier, France., Verbraecken J; Multidisciplinary Sleep Disorders Center, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium.; University of Antwerp, Antwerp, Belgium., Partinen M; Helsinki Sleep Clinic, Vitalmed Research Center, Helsinki, Finland.; Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland., Hedner J; Sleep and Vigilance Laboratory, Department of Internal Medicine, University of Göteborg, Sahlgrenska University Hospital, University of Göteborg, Göteborg, Sweden., Saaresranta T; Sleep Research Center, Department of Pulmonary Diseases and Clinical Allergology, University of Turku, Turku, Finland.; Department of Pulmonary Diseases, Turku University Hospital, Turku, Finland., Georgiev O; Pulmonology Unit, Department of Internal Medicine, Alexandrovska Hospital Medical University, Sofia, Bulgaria., Tiholov R; Department of Internal Diseases, Sveti Ivan Rilski Multiprofile Hospital for Active Treatment, Kozloduy, Bulgaria., Lecomte I; Bioprojet, 30 rue Francs Bourgois, Paris, France., Tamisier R; Hypoxia-Physiopathology (HP2) Laboratory, INSERM U1042, University Grenoble Alpes, Grenoble, France; and.; Cardio-Respiratory Functional Exploration Laboratory (EFCR), Grenoble Alpes University Hospital, Grenoble, France., Lévy P; Hypoxia-Physiopathology (HP2) Laboratory, INSERM U1042, University Grenoble Alpes, Grenoble, France; and.; Cardio-Respiratory Functional Exploration Laboratory (EFCR), Grenoble Alpes University Hospital, Grenoble, France., Scart-Gres C; Bioprojet, 30 rue Francs Bourgois, Paris, France., Lecomte JM; Bioprojet, 30 rue Francs Bourgois, Paris, France., Schwartz JC; Bioprojet, 30 rue Francs Bourgois, Paris, France., Pépin JL; Hypoxia-Physiopathology (HP2) Laboratory, INSERM U1042, University Grenoble Alpes, Grenoble, France; and.; Cardio-Respiratory Functional Exploration Laboratory (EFCR), Grenoble Alpes University Hospital, Grenoble, France. |
| Abstrakt: |
Rationale: Excessive daytime sleepiness is a common disabling symptom in obstructive sleep apnea syndrome. Objectives: To evaluate the efficacy and safety of pitolisant, a selective histamine H3 receptor antagonist with wake-promoting effects, for the treatment of daytime sleepiness in patients with moderate to severe obstructive sleep apnea refusing continuous positive airway pressure treatment. Methods: In an international, multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial, pitolisant was individually titrated at up to 20 mg/d over 12 weeks. The primary endpoint was the change in the Epworth Sleepiness Scale score. Key secondary endpoints were maintenance of wakefulness assessed on the basis of the Oxford Sleep Resistance test, safety, Clinical Global Impression of severity, patient's global opinion, EuroQol quality-of-life questionnaire, and Pichot fatigue questionnaire. Measurements and Main Results: A total of 268 patients with obstructive sleep apnea (75% male; mean age, 52 yr; apnea-hypopnea index, 49/h; baseline sleepiness score, 15.7) were randomized (200 to pitolisant and 68 to placebo) and analyzed on an intention-to-treat basis. The Epworth Sleepiness Scale score was reduced more with pitolisant than with placebo (-2.8; 95% confidence interval, -4.0 to -1.5; P < 0.001). Wake maintenance tests were not improved. The Pichot fatigue score was reduced with pitolisant. The overall impact of pitolisant was confirmed by both physicians' and patients' questionnaires. Adverse event incidence, mainly headache, insomnia, nausea, and vertigo, was similar in the pitolisant and placebo groups (29.5% and 25.4%, respectively), with no cardiovascular or other significant safety concerns. Conclusions: Pitolisant significantly reduced self-reported daytime sleepiness and fatigue and improved patient-reported outcomes and physician disease severity assessment in sleepy patients with obstructive sleep apnea refusing or nonadherent to continuous positive airway pressure.Clinical trial registered with www.clinicaltrials.gov (NCT01072968) and EU Clinical Trials Register (EudraCT 2009-017251-94). |
