26 Sep Large Trial Evaluates Inhaled Nitric oxide on Survival Without Pulmonary Dysplasia in Preterm Infants
MedicalResearch.com Interview with:
Shabih U. Hasan, MD, DCH, FRCPC
Professor and Staff Neonatologist, Alberta Health Services
Department of Pediatrics, Cumming School of Medicine
University of Calgary
MedicalResearch.com: What is the background for this study?
Response: Approximately 8% of all infants are born prematurely (preterm birth <37 weeks postmenstrual age). Preterm infants have many challenges including establishment of adequate pulmonary gas exchange. Due to not yet fully developed lungs, preterm infants require respiratory support consisting of respirators and other forms of non-invasive ventilation modalities and supplemental oxygen. Bronchopulmonary dysplasia (BPD) is the commonest morbidity among very low birth weight infants as 40% of survivors at postmenstrual age <30 weeks develop BPD. This is a serious condition as it can lead to short- and long-term pulmonary complications, increased hospital visits and neurodevelopmental impairment. BPD is defined where preterm infants require respiratory support and/or supplemental oxygen at 36 weeks postmenstrual age.
A number of therapeutic and non-therapeutic modalities have been used to prevent BPD including inhaled nitric oxide (iNO). In 2006, the NO CLD trial demonstrated that iNO prevented BPD (Relative benefit 1.81; CI 1.27-2.59, P = 0.006) if used according to the NO CLD Protocol (Ballard et al., New England Journal of Medicine, 355:343-353, 2006). Our study (NEWNO; Newborns treated with Nitric Oxide) was designed to replicate the NO CLD study.
MedicalResearch.com: What are the main findings?
Response: This is a multicenter, double-masked, placebo-controlled randomized clinical trial that did not replicate the NO CLD results.
Our study followed the NO CLD protocol and had twice as many infants in each arm yet demonstrated no benefit either on the 1) survival without BPD, 2) one year outcomes or 3) neurodevelopmental outcomes at 18-24 months of age.
MedicalResearch.com: What should clinicians and patients take away from your report?
Response: iNO, initiated at 20 ppm at 5-14 days of age to high-risk preterm infants and continued for 24 days did not improve survival without BPD, nor respiratory or neurodevelopmental outcomes at 18‑24 months of age. Thus, going forward, iNO should not be used in the context of BPD prevention in general preterm population.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: In the post-hoc analysis, the NO CLD study showed that the relative benefits of iNO were limited to the non-white population. Thus, genetic predisposition analysis needs to performed that might identify which infants would benefit from iNo treatment. Secondly, an RCT restricted to the non-white and/or black population might be warranted
MedicalResearch.com: Is there anything else you would like to add?
Response: The RCTs that demonstrate benefits need to be replicated at least once to ensure that the results from the initial study hold true.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Hasan SU, Potenziano J, Konduri GG, Perez JA, Van Meurs KP, Walker MW, Yoder BA, for the Newborns Treated With Nitric Oxide (NEWNO) Trial Group. Effect of Inhaled Nitric Oxide on Survival Without Bronchopulmonary Dysplasia in Preterm InfantsA Randomized Clinical Trial. JAMA Pediatr. Published online September 25, 2017. doi:10.1001/jamapediatrics.2017.2618
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