Sweep Gas Nitric Oxide During Extracorporeal Membrane Oxygenation in Neonates and Children (NECTAR Trial): A Single-Center, Pilot Randomized Controlled Trial

Objectives: To test the feasibility and safety of a randomized controlled trial (RCT) delivering nitric oxide into the sweep gas of extracorporeal membrane oxygenation (ECMO) circuits (sNO) in critically ill children. Second, we explored whether use of sNO may influence clinical outcomes. Design: Prospective pilot single-center open-label RCT (trial registration number ACTRN12619001518156). Setting: Single-center, tertiary PICU with enrollment between July 2020 and July 2023. Patients: Patients from birth to 16 years requiring venoarterial or venovenous ECMO support were enrolled. Interventions: Randomization to sweep flow with an oxygen/nitrogen mix vs. a mix of oxygen, nitrogen and sNO (20 parts per milliion). Randomization was stratified by type of ECMO support (venoarterial vs. venovenous). Measurements and Main Results: Of 60 eligible patients 53 underwent randomization. The median (interquartile range IQR) was 1 month (0.1–33.5 mo) and 6.2 months (0.5–120.2 mo) for the intervention and control arms, respectively. Venoarterial and venovenous support were used in 35 of 53 (65%) and 18 of 53 (35%) patients, respectively. In all, 17 of 53 (32%) received pulmonary, 23 of 53 (43%) cardiac and 13 of 53 (25%) extracorporeal cardiopulmonary resuscitation support. Median (IQR) survival free of ECMO and survival free of PICU censored at 30 and 90 days were similar: 18.2 days (0–25.2 d) and 69.1 days (0–85.2 d) vs. 20.8 days (0–26.3 d) and 77.7 days (0–85.9 d) with an effect estimate of –3.2 days (–16.6 to 10.1 d) and –8.8 days (–54.2 to 36.6 d) between the intervention and standard care arm. Blood product use, circuit duration to replacement, free plasma hemoglobin, degree of oxygenator thrombus, and incidence of methemoglobinemia were similar between the two groups. No major adverse events occurred related to the treatment allocation or intervention. Conclusions: This single-center pilot RCT of sNO vs. standard sweep flow in the ECMO circuit demonstrated that such a trial is safe and feasible. However, given no effect of sNO on clinical outcomes was detected further exploration of dose and route of administration of NO should be undertaken before larger, definitive trials are conducted.