567 - High continuous positive airway pressure (≥9 cmH2O) vs. nasal intermittent positive pressure ventilation in preterm neonates: A multi-centre pilot randomized controlled trial

Publication Number: 567.5332

Amit Mukerji, McMaster University, Hamilton, ON, Canada; Emily Rempel, McMaster University Michael G. DeGroote School of Medicine, Cayuga, ON, Canada; Lehana Thabane, McMaster University/St Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada L8N 4A6, ON, Canada; Heather Johnson, McMaster University Michael G. DeGroote School of Medicine, Hamilton, ON, Canada; Georg Schmolzer, University of Alberta Faculty of Medicine and Dentistry, Edmonotn, AB, Canada; Brenda H. Law, University of Alberta Faculty of Medicine and Dentistry, Edmonton, AB, Canada; Pranav Jani, Westmead Hospital and University of Sydney, Westmead, New South Wales, Australia; Mark B. Tracy, The University of Sydney, Sydney, New South Wales, Australia; Catherine Rottkamp, University of California, Davis, School of Medicine, Sacramento, CA, United States; Martin Keszler, The Warren Alpert Medical School of Brown University, North Kingstown, RI, United States; Haresh Kirpalani, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Prakesh S. Shah, Mount Sinai Hospital, Toronto, ON, Canada

Background: Nasal continuous positive airway pressure (CPAP) at a constant distending pressure of 5-8 cmH2O is the standard non-invasive respiratory support for preterm infants. When such CPAP pressures are insufficient, nasal intermittent positive pressure ventilation (NIPPV) is often used. In recent years, High CPAP (≥9 cmH2O) has emerged as an alternative. However, the comparative risks and benefits of High CPAP vs. NIPPV are unknown.

Objective: This pilot trial aimed to assess the feasibility of a larger, definitive randomized clinical trial (RCT) comparing High CPAP vs. NIPPV. Our secondary objective was to compare clinical outcomes.

Design/Methods: This unblinded RCT was conducted at 4 tertiary NICUs (NCT03512158). Eligible infants were < 29 weeks’ GA who either failed treatment with traditional CPAP (≤8 cmH2O) or were being extubated to post-extubation mean airway pressure (Paw) ≥9 cmH2O. Following consent, infants were randomized to either High CPAP (9-15 cmH2O) or NIPPV (target Paw 9-15 cmH2O). Randomization was stratified by site and GA ( < 26 vs. 26-28 weeks). The primary outcome was feasibility of a definitive trial, defined as >10% of eligible infants being randomized and protocol violations < 20% of all consented/randomized infants. Main secondary outcome was failure of assigned treatment ≤7 days post-randomization (defined as: intubation, escalation beyond pre-specified pressure limits, or ‘rescue’ cross-over with an alternate mode. Additional outcomes included intubation ≤7 days, moderate-severe bronchopulmonary dysplasia (BPD) and pneumothorax.

Results: From May 2018–Sept 2024 (extended due to COVID-19) 974 infants < 29 weeks’ GA were admitted at participating sites and screened; 764 were eligible. Of these 210 consented, of which 100 infants were randomized (High CPAP (N=48) or NIPPV (N=52)), yielding a randomization rate of 13% (100/764), Figure 1. There were no baseline differences between the two groups (Table 1). The pre- and post-randomization protocol violation rates were 9% (18/210) and 15% (15/100), respectively (Table 2). The incidence of failure ≤7 days was 63% (30/48) for High CPAP vs. 54% (28/52) for NIPPV (OR 1.42; 95% CI: 0.62, 3.17). Incidence of intubation ≤7 days was 44% (21/48) vs. 40% (21/52) with High CPAP vs. NIPPV (OR 1.15; 95% CI: 0.52, 2.54). No differences were noted in any additional outcomes (Table 2).

Conclusion(s): This multi-centre pilot RCT demonstrates the feasibility of conducting a definitive trial comparing High CPAP (≥9 cmH2O) vs. NIPPV. While no significant differences in clinical outcomes were noted in this pilot trial, further adequately-powered studies are needed.

Figure 1
Clean Consort Diagram 20241104_PASversion.pdfCONSORT patient flow diagram

Table 1
Table 1_PAS_20241101.pdfDemographic and baseline characteristics of randomized participants

Table 2
Table 2_PAS_20241101.pdfPrimary (feasibility) and secondary (clinical) outcomes