Effect of Upper Airway Stimulation in Patients with Obstructive Sleep Apnea (EFFECT): A Randomized Controlled Crossover Trial

Abstract

Background: Several single-arm prospective studies have demonstrated the safety and effectiveness of upper airway stimulation (UAS) for obstructive sleep apnea. There is limited evidence from randomized, controlled trials of the therapy benefit in terms of OSA burden and its symptoms. Methods: We conducted a multicenter, double-blinded, randomized, sham-controlled, crossover trial to examine the effect of therapeutic stimulation (Stim) versus sham stimulation (Sham) on the apnea-hypopnea index (AHI) and the Epworth Sleepiness Scale (ESS). We also examined the Functional Outcomes of Sleep Questionnaire (FOSQ) on sleep architecture. We analyzed crossover outcome measures after two weeks using repeated measures models controlling for treatment order. Results: The study randomized 89 participants 1:1 to Stim (45) versus Sham (44). After one week, the AHI response rate was 76.7% with Stim and 29.5% with Sham, a difference of 47.2% (95% CI: 24.4 to 64.9, p < 0.001) between the two groups. Similarly, ESS was 7.5 ± 4.9 with Stim and 12.0 ± 4.3 with Sham, with a significant difference of 4.6 (95% CI: 3.1 to 6.1) between the two groups. The crossover phase showed no carryover effect. Among 86 participants who completed both phases, the treatment difference between Stim vs. Sham for AHI was −15.5 (95% CI −18.3 to −12.8), for ESS it was −3.3 (95% CI −4.4 to −2.2), and for FOSQ it was 2.1 (95% CI 1.4 to 2.8). UAS effectively treated both REM and NREM sleep disordered breathing. Conclusions: In comparison with sham stimulation, therapeutic UAS reduced OSA severity, sleepiness symptoms, and improved quality of life among participants with moderate-to-severe OSA.

Randomised, controlled crossover trial of intermittent and continuous transcutaneous electrical stimulation of the genioglossus muscle for obstructive sleep apnoea

“…GG muscle dysfunction closes the upper airways during sleep; therefore, enhancing GG tone is an emerging alternative treatment for OSA 3 27. To reduce OSA severity in selected OSA cases,28–31 HGNS has been implemented in clinical practice for patients with moderate to severe OSA who cannot adhere to CPAP 26. However, HGNS is limited by being invasive, costly and having only limited indications 4 5.…”

Patienten relevanter Nutzen und Therapieeffekte in der Stimulationstherapie bei schlafbezogenen Atmungsstörungen

“…On one hand, there are the cohort studies entitled STAR 24 38 39 40 and the German Postmarket study 31 41 42 43 as well as the registry study called ADHERE 44 45 including the prospective comparative study 46 initiated and supported by the manufacturer of Inspire Medical Company. On the other hand, there are independent cohort trials of larger implantation centers with sometimes several years of follow-up examinations 47 48 49 50 51 and the randomized controlled therapy withdrawal study of EFFECT 52 .…”

“…Inspire Medical initiierten und unterstützten prospektiven Kohortenstudien STAR 24 38 39 40 und die German-Postmarket Studie 31 41 42 43 sowie die Registerstudie ADHERE 44 45 inklusive der prospektiven Vergleichsstudie im Wartearmdesign 46 . Zum anderen gibt es unabhängige Kohortenstudien von größeren Implantationszentren mit teilweise mehrjährigen Nachuntersuchungen 47 48 49 50 51 und die randomisierte kontrollierte Therapieentzugsstudie EFFECT 52 .…”

“…18,0 [38,40]. Dieser Unterschied von gut 2 Punkten wurde auch in der randomisiert-kontrollierten Therapieentzugsstudie EFFECT herausgearbeitet [52]. Die Substudie des ADHERE-Registers verwendete in dem prospektiven Vergleich zwischen der Therapiegruppe und den HNS-Kandidaten im Wartearm die Kurzfassung des FOSQ, den FOSQ-10 [46].…”

Die Hypoglossus-Stimulation zur Therapie der obstruktiven Schlafapnoe

“…unbehandelten Patienten bestätigte den positiven Effekt der Therapie [16]. Kürzlich konnte die trizentrische deutsche EFFECT-Studie mit einer subtherapeutischen Stimulation als Kontrolle in einem randomisierten Cross-over-Design mit 89 Patienten auf höchstem Evidenzlevel belegen, dass die Verbesserung der Symptomatik und der polysomnografischen Parameter der Stimulationstherapie selbst zuzuschreiben ist [17]. Die Ergebnisse der ADHE-RE-Registerstudie von Patienten (mehr als 50 % davon mit Komorbiditäten) zeigten an zuletzt 1849 Patienten 1 Jahr eine Reduktion des AHI von 36,0 ± 15,7/h auf 14,5 ± 15,0/h, des ESS von 11,2 ± 5,6 auf 7,1 ± 4,6 bei einer Nutzung von 44,9 ± 15,3 h/Woche.…”