The THN3 trial shows that the pHGNS device is safe, effective, and well-tolerated for OSA with a stable long-term profile.Proximal hypoglossal nerve stimulation (pHGNS) delivers durable improvements in patients with obstructive sleep apnoea (OSA) in the phase III THN*3 trial.
“[P]articipants sustained long-term improvements in sleep-disordered breathing, sleep quality and continuity, and associated patient-reported outcomes for at least 3 years,” the investigators said.
The device was activated 1 month (n=92) or 4 months (n=46) after implantation in 138 participants (mean age 55.5 years, 86.2 percent men, mean BMI 29.84 kg/m2). Follow-ups were done at months 12 and 15 (M12/15) in the 1- and 4-month groups, respectively. Long-term efficacy was evaluated annually for 3 years (M36). Three-quarters of the participants completed the M36 follow-up. [Chest 2026;169:1357-1370]
Median AHI** decreased with pHGNS from baseline to M12/15 and M36 (from 36.5 to 19.6 and 18.9 events/hr). According to the researchers, these were largely due to reductions in hypopneas rather than apnoeas, suggesting that THN was most effective in restoring patency of a partially rather than a completely obstructed airway.
From M12/15 to M36, median supine (from 50.7 to 48.4 events/hr) and non-supine AHI (from 16.2 to 14.5 events/hr) improved, as did median REM*** (from 27.7 to 22.2 events/hr) and non-REM AHI (from 18.5 to 17.3 events/hr). The augmented responses in the non-supine position may be due to the lower baseline pharyngeal collapsibility or greater reductions in collapsibility with THN. [Chest 2000;118:1031-1041]
Compared with baseline, M12/15 and M36 saw sustained reductions in median N1% of total sleep time (22 percent vs 15.3 percent and 13.2 percent) and median arousal index (57.4 vs 40.1 and 35.8 events/hr). There were also increases in median N2% (58.6 percent vs 60 percent and 63.7 percent) and REM% of total sleep time (15.8 percent vs 17.1 percent and 18.4 percent), suggesting a shift in continuous deeper stages of sleep on THN.
“Concomitant reductions in respiratory and non-respiratory arousal indices suggest that improvements in sleep architecture can be attributed to sustained increases in sleep continuity from THN, and that it did not arouse participants excessively,” the investigators said.
Stimulation levels were stable, with the means not substantially changing from M12/15 to M36 (motor level: from 346.1 to 345.1 µA; therapeutic level: from 423 to 385.1 µA; sensory limit: from 458.3 to 426.8 µA). “Stable neuromotor responses suggest that tachyphylaxis, stimulus habituation, or increased impedance from fibrotic ingrowth between the nerve and electrodes were lacking,” they noted.
The most common serious adverse events (AEs) were other OSA surgery (3.6 percent) and device explantation (2.9 percent). The most common non-serious device-related AE was stimulation-related discomfort (29 percent).
Patient-reported outcomes
The mean ESS# (from 11.2 to 6.6 and 6.5), FOSQ-10# (from 15 to 18 and 18.3), and SOS# (from 28.9 to 64 and 59.4) also improved from baseline to M12/15 and M36. “[These] exceeded the benchmark minimum clinically important differences of 2–3, 1.7–2, and 7.6 points, respectively,” the researchers said.
Between baseline and M36, more patients reported normal ESS (from 39.7 percent to 75.5 percent) and FOSQ (from 20.7 percent to 73.5 percent) and rated their snoring intensity in the last 4 weeks as ‘none’ or ‘mild’ (from 5.5 percent to 44.2 percent).
Approximately 82 percent of participants indicated that therapy was ‘very easy’ or ‘easy’ to use for ≥5 nights per week through M36. Patient perceptions were generally positive: 81.6 percent reported they were ‘satisfied’ or ‘very satisfied’, 89.8 percent stated they would do it again, and 91.8 percent noted they would recommend pHGNS to a friend.
Stable long-term profile
The pHGNS device targets portions of the proximal hypoglossal nerve trunk for stimulating the protrusor and retractor muscle fibres that primarily stabilize and stiffen the tongue. [J Clin Sleep Med 2023;19:947-955; Neuromodulation 2013;16:376-386; JAMA Otolaryngol Head Neck Surg 2023;149:512-520]
“[The study shows that] pHGNS is a safe, effective, and well-tolerated treatment for moderate-to-severe OSA with a stable long-term profile,” the investigators said.