Optimising Breathing Support at Extubation in Very Preterm Infants: A Clinical Study

The PrePAP trial will investigate if extubation with prePAP (nCPAP commenced prior to extubation) compared to standard extubation practice (nCPAP commenced after extubation) reduces oxygen desaturation in the four hours immediately post-extubation, in very preterm infants being extubated for the first time within the first 30 days of life. Many infants born very preterm (\<32 weeks' gestation) are intubated at birth to receive respiratory support via invasive ventilation. While essential for survival, invasive ventilation can injure their underdeveloped lungs, disrupt lung development and increase the risk of bronchopulmonary dysplasia, a major cause of long-term respiratory morbidity. Transitioning infants to non-invasive ventilation as soon as feasible is prioritised by clinicians. However, in very preterm infants, almost 40% of extubation attempts fail due to oxygen desaturation or lung collapse. Re-intubation due to extubation failure can induce further airway injury, cardiovascular instability, and oxygen desaturation, resulting in clinical deterioration and prolonged hospitalisation. PrePAP has been recently suggested as a method of improving respiratory stability during extubation in preterm infants. PrePAP involves commencing nCPAP prior to extubation, with the intent to maintain lung volumes during extubation; preserving oxygenation from pre- to post-extubation. To date, there isn't any clinical evidence explaining the impact to the lungs when both mechanical ventilation and nCPAP are being applied, nor is there evidence that signals a benefit of using prePAP during extubation. Despite this, prePAP is already used in clinical practice and is described in certain neonatal intensive care unit (NICU) extubation guidelines in Australia. The PrePAP trial is a prospective, multicentre, unblinded, randomised, controlled trial comparing extubation from mechanical ventilation to nCPAP with and without the application of prePAP in very preterm infants born \<30 weeks gestational age at first extubation. Very preterm infants who meet all inclusion (and no exclusion) criteria will be randomised to receive one of two extubation procedures, placing them in either the "Extubation with prePAP" arm or the "Extubation without prePAP" arm: 1. Arm 1: Extubation with prePAP (intervention): nCPAP commenced prior to endotracheal tube removal 2. Arm 2: Extubation without prePAP (control): nCPAP commenced following endotracheal tube removal For both arms, the intervention period will begin with a 2-to-5-minute pre-extubation period (whilst the infant is still ventilated), followed by a post-extubation period of up to 4 hours, and a follow-up period of up to 7 days (168 hours). The primary outcome (lowest S/F ratio) is assessed only during the (up to) 4-hour post-extubation period. The results of this trial will determine the appropriate clinical outcomes and end point for a definitive, larger randomised trial to inform clinical practice.