Continued Pressure for Alveolar Protection: A Randomized Controlled Trial (CPAP Trial)

Research Triangle Institute, Durham NC

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Abstract

PROJECT SUMMARY/ABSTRACT Bronchopulmonary dysplasia (BPD) affects 50% of all preterm infants <29 weeks’ gestation and is associated with long-term respiratory morbidity, neurodevelopmental impairment, and mortality. With improving survival of more preterm infants caused by advances in neonatal care, the rates of BPD and post- prematurity respiratory disease (PPRD) are increasing. Longer-term lung health trajectories and pulmonary function among survivors of prematurity have also not improved in recent decades. CPAP is among the most commonly used modes of respiratory support for very preterm infants that minimizes exposure to ventilator- associated lung injury. Substantial animal data indicate that CPAP-induced mechanical strain promotes compensatory lung growth in neonatal models of lung disease. Furthermore, recent clinical data suggest that extending CPAP for 2 additional weeks among very preterm infants meeting criteria for CPAP cessation increases lung and alveolar volumes and may improve short-term pulmonary outcomes. It is thus important to test extending the duration of CPAP in a sufficiently large population of preterm infants at highest risk of adverse outcomes to provide robust data to determine the benefits and risks of such a strategy. To address this unmet clinical need, we will conduct the Continued Pressure for Alveolar Protection: A Randomized Controlled Trial (CPAP trial), a scientifically rigorous multicenter trial among infants <29 weeks’ gestation and <32 weeks’ post menstrual age (PMA) who meet typical criteria for CPAP cessation to determine whether extending CPAP until 34 weeks’ PMA or for at least 2 additional weeks compared with weaning to nasal cannula reduces respiratory morbidity. We will test the following two hypotheses that extending CPAP until 34 weeks’ PMA or for at least 2 additional weeks will (1) decrease BPD or death at 36 weeks’ PMA and (2) decrease PPRD at 22 to 26 months follow-up. Our study is powered to detect a clinically meaningful reduction in rates of BPD or death using a five-level ordinal outcome. PPRD will be assessed using a modified ISAAC (International Study of Asthma and Allergies in Childhood) questionnaire at 22 to 26-months follow up. The key innovation of this project is the application of extended CPAP, which may promote lung growth in infants with lung disease who would usually be weaned to a nasal cannula. The Neonatal Research Network has an excellent track record of enrolling high-risk infants in rigorous clinical trials of respiratory interventions with successful participant retention at follow-up. Successful completion of this trial will establish whether extending the duration of CPAP benefits extremely preterm infants compared with weaning to nasal cannula, once typical CPAP cessation criteria are met, thus providing the data necessary to inform key perinatal guidelines of respiratory support in very preterm infants. If extending CPAP reduces respiratory morbidity in preterm infants <29 weeks’ gestation, this intervention could be readily implemented worldwide among preterm infants with respiratory distress syndrome to improve future lung health.