JMIR Publications

ABSTRACT

Background:

Extracorporeal Membrane Oxygenation (ECMO) provides support for the pulmonary or cardiovascular function of children where the predicted mortality risk is very high. Activation of the host inflammatory response as well as the coagulation cascade due to the extracorporeal circuit contributes to morbidity and mortality in these patients. Mixing of nitric oxide (NO) into the sweep gas of ECMO circuits may reduce ECMO-induced inflammation and clotting activation. We hypothesize that mixing NO into the sweep gas during ECMO support is safe and decreases both inflammatory as well as coagulation cascade activation pathways, leading to improved outcomes.

Objective:

To test in a pilot randomised controlled trial the feasibility, safety and effect of NO, mixed into the sweep gas of ECMO systems, during ECMO treatment in neonates and children.

Methods:

The NECTAR trial is an open label, randomised, controlled, parallel-group pilot trial to be conducted in a single centre institution. Fifty patients who require ECMO support will be randomly assigned to NO mixed into the sweep gas of the ECMO system at 20ppm for the duration of ECLS or standard care (no NO) in a 1:1 ratio with stratification by support type (Veno-venous vs veno-arterial ECLS).

Results:

Outcome measures will focus on feasibility (protocol fidelity, recruitment rate and refusal to participate rate), safety (sweep gas delivery failure, CO2 control and methaemoglobin levels) and efficacy (host inflammation, coagulation activation, clotting and bleeding complications and blood product use). Clinical outcomes include survival free of ECMO and PICU, respectively, hospital length of stay, and long-term outcomes include neurodevelopment and quality of life. Oxygenators will be scanned by computer tomography for clot assessment. Analyses will be conducted on an intention to treat basis.

Conclusions:

The NECTAR study investigates the safety, feasibility and explores efficacy of a drug intervention during extracorporeal life support to improve morbidity and mortality in patients treated with ECMO. The intervention targets adverse outcomes in patients who are supported by ECLS and who have a high expected mortality and morbidity. The study includes assessment of cytokines, chemokines and coagulation factors to assess the impact of NO on inflammation and coagulation. The study will be one of the largest randomised controlled trials performed in paediatric patients supported by ECMO. Clinical Trial: The study was approved by the local HREC (HREC/18/QCHQ/49018) and has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619001518156). The NECTAR trial commenced recruitment in August 2020.