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Heated Humidified High-Flow Nasal Cannula for Prevention of Extubation Failure in Preterm Infants. OBJECTIVES: To compare extubation failure rate between the heated humidified high-flow nasal cannula (HHHFNC) and continuous positive airway pressure (CPAP) groups. METHODS: Intubated infants with gestational age (GA) <32 wk, who were ready to extubate, were randomized to receive respiratory support with either CPAP or HHHFNC after extubation. In CPAP group, nasal mask CPAP with preset pressure and fraction of inspired oxygen (FiO2) equal to positive end-expiratory pressure (PEEP) and FiO2 of ventilator before extubation was applied. In the HHHFNC group, predefined flow rate according to the protocol was applied. Primary outcome was extubation failure within 72 h after endotracheal tube removal. RESULTS: Forty-nine infants were enrolled; 24 in the HHHFNC and 25 in the CPAP group. Baseline demographic and respiratory conditions before extubation were similar. There was no difference in infants who met failed extubation criteria between the two groups [8 (33%) in HHHFNC vs. 6 (24%) in CPAP group (p = 0.47)]. However, 6 infants (75%) in HHHFNC and 4 infants (66%) in CPAP group who met failed extubation criteria could be rescued by bilevel CPAP. Therefore, the reintubation rate was comparable [2 infants (8.3%) in HHHFNC vs. 2 infants (8%) in CPAP group]. Morbidities or related complications were not different but infants in the HHHFNC group had significantly less nasal trauma (16.7% vs. 44%; p = 0.03). CONCLUSIONS: In the index study, the extubation failure rate was not statistically different between infants who were on HHHFNC or CPAP support.