An $11.4 million grant from the National Institutes of Health (NIH) will fund a multi-institutional clinical trial to study the effectiveness of nitric oxide in treating newborns with congenital diaphragmatic hernia (CDH). The seven-year NoNO Trial aims to determine if the longstanding practice of using nitric oxide improves outcomes for these critically ill infants.
The trial, led by Dr. Tim Jancelewicz at the University of Tennessee Health Science Center and Dr. Matthew Harting at the University of Texas Health Science Center at Houston, involves 19 partnering institutions. CDH, a condition affecting approximately one in 2,000 to one in 4,000 live births, occurs when the diaphragm doesn't fully develop, leading to underdeveloped lungs and pulmonary hypertension.
Trial Design and Objectives
The NoNO Trial will employ a randomized de-implementation design. Participating centers will be randomized to either continue using nitric oxide as usual or to discontinue its use. This approach allows each center to serve as its own control, comparing outcomes before and after the de-implementation of nitric oxide.
"The only difference in care will be that nitric oxide is removed and you’ll be able to compare outcomes before and after de-implementation at each center," explained Dr. Jancelewicz. The primary goal is to assess whether nitric oxide improves oxygenation and reduces the need for extracorporeal membrane oxygenation (ECMO), a highly invasive intervention.
Addressing Controversies and Barriers
Historically, nitric oxide has been used to improve oxygenation in newborns with CDH, with the belief that it could decrease the need for ECMO. However, recent evidence suggests that nitric oxide may not provide a survival advantage. The trial will also explore the reasons why physicians continue to use nitric oxide despite the lack of definitive evidence supporting its use.
The trial will include interviews with physicians to understand the barriers to de-implementation of nitric oxide. "The heart of this trial is really the design to try and overcome historic barriers in CDH research and answer some key patient management questions," Dr. Jancelewicz stated.
Significance and Future Directions
The results of the NoNO Trial are expected to provide valuable insights into the optimal management of newborns with CDH. If successful, this approach can be applied to other complex neonatal diseases where care practices are not always evidence-based. According to Dr. Jancelewicz, "If we get an answer for this question, we can then ask other questions using this approach in other neonatal diseases where the care is very complex."
