Jaroonpipatkul A.Kaeoperm P.Promlee N.Srilam W.Pakdeewongse S.Tongyoo S.Rittayamai N.Mahidol University2026-02-282026-02-282026-01-01Pulmonology Vol.32 No.1 (2026)25310429https://repository.li.mahidol.ac.th/handle/123456789/115427Background: Low-level pressure support ventilation (PSV) is the usual first spontaneous breathing trial (SBT) method. High-flow oxygen therapy (HFOT) via a dedicated connector through an endotracheal tube might be a credible alternative during SBT. This study aimed to compare the rate of SBT success between HFOT and low-level PSV. Methods: We conducted a two-centre, open-label, non-inferiority randomised controlled trial. Adults mechanically ventilated patients for at least 24 hours and ready to wean were randomised to 30-minute SBTs with HFOT or low-level PSV. The primary outcome was SBT success rate (non-inferior margin of 10%). Extubation rate within 48 hours following successful SBT, reintubation rate within 48 hours after extubation, and hospital mortality were the exploratory outcomes. Results: Among 162 enrolled patients, 81 received HFOT and 81 received low-level PSV. SBT succeeded in 77/81 patients (95.1%) in each arm (absolute difference 0.0%; 95% confidence interval [CI] −7.2 to 7.2; p = 1.000). No significant differences between HFOT and low-level PSV in extubation rates following successful SBT (88.3% vs 80.5%, respectively; p = 0.183) or reintubation rates within 48 hours after extubation (8.8% vs 17.7%, respectively; p = 0.140). Hospital mortality was lower with HFOT than with low-level PSV (11.1% vs 24.7%, respectively; difference −13.6%; 95% CI −25.2 to −2.0; p = 0.024). Conclusion: Among mechanically ventilated patients meeting weaning criteria, HFOT demonstrated non-inferiority to low-level PSV for SBT success rates. Extubation and 48-hour reintubation rates were similar. Clinical Trial Registration: Thai Clinical Trials Registry; registration number: TCTR20190703002; URL: www.thaiclinicaltrials.org.MedicineArticleSCOPUS10.1080/25310429.2026.26305282-s2.0-1050305306692531043741705571