Sulthiame (STM), a potent carbonic anhydrase inhibitor, reduced the apnea-hypopnea index (AHI) in patients with obstructive sleep apnea (OSA). (Hedner et al. AJRCCM, in press)
We studied the effect of STM on sleep quality assessed by cardiopulmonary coupling (CPC) in moderate-to-severe OSA patients.
Post-hoc analysis of a double-blind, placebo-controlled, phase IIb trial (n=58, 72% male, age 60±10 years, body mass index 28±3 kg/m², AHI 56±22 events/h). Patients were randomized to receive placebo (n=22), STM 200 mg (n=11), or STM 400 mg (n=25), respectively. Polysomnography recordings were performed at baseline and after 4 weeks of intervention. The electrocardiography signal from sleep studies was used for CPC analysis. The proportion of high-frequency coupling (HFC, stable sleep), low-frequency coupling (LFC, unstable sleep), elevated-LFC narrow-band (e-LFC_NB, marker of periodic breathing) and elevated-LFC broad-band (e-LFC_BB, sleep fragmentation) was calculated. Quality of life was assessed by Functional Outcomes of Sleep Questionnaire (FOSQ). The changes in CPC variables between STM 200/400 mg and placebo from baseline to post-treatment were analyzed using analysis of covariance.
Baseline AHI and CPC parameters did not differ between groups. Compared to placebo, STM 200 mg significantly reduced LFC (0.9±11.4 vs.12.2±16.0%, p=0.026) and e-LFC_BB (0.4±8.5 vs. 9.1±4.5%, p=0.003). The corresponding changes for STM 400 mg were 6.7±11.3% and 4.8±10.5%, (p=0.089 and 0.13, respectively). HFC and e-LFC_NB did not change significantly by the STM treatment. Improving HFC, LFC and e-LFC_BB were associated with improvement of FOSQ total score after STM treatment (n=36, Spearman correlation, r=0.44, 0.40 and 0.36, p=0.007, 0.015 and 0.032, respectively).
4-week treatment of STM 200 mg was associated with improved sleep quality assessed by CPC. Nocturnal CPC analysis may provide unique information on patient-reported outcome measures in OSA patients. (EudraCT: 2017-004767-13)
The clinical trial was funded by Desitin GmbH and the CPC analysis work was supported by the Erik & Lily Philipsons memorial fund and Swedish Heart Lung Foundation (project 20210500).