Prolonged Outcomes After Nitric Oxide (PrONOx)
Prolonged Outcomes After Nitric Oxide (PrONOx)
The purpose of this study is to look at the long term consequences of prematurity in infants
 treated with inhaled nitric oxide (iNO) while in the neonatal intensive care unit.
Prematurity-associated respiratory failure is a growing public health problem. Although
 mortality has dropped with advances in perinatal care, this condition consumes considerable
 healthcare resources and is increasingly associated with worrisome long-term morbidity,
 developmental delay, and family burden. Inhaled nitric oxide (iNO), a selective pulmonary
 vasodilator that improves short-term outcomes in term neonates with respiratory failure, may
 benefit premature infants. Consequently, a NHLBI-funded randomized controlled trial (iNO RCT-
 NHLBI U01 HL064857) is assessing the effect of iNO on the combined end-point of mortality or
 oxygen dependency at 36 weeks post conceptional age in 800 infants with
 prematurity-associated respiratory failure.

 However, prematurity-associated respiratory failure has a different etiology from respiratory
 failure in term infants and the wide array of long-term consequences that may be affected by
 iNO are not captured under the existing study design.

 We therefore are extending and enhance the follow-up of the NHLBI iNO RCT. Specifically, we
 are assessing the effects of INO use on: #1. - long-term clinical and childhood developmental
 outcomes; #2. - family burden, and; #3. - healthcare costs of prematurity-associated
 respiratory failure. Under aim #4, we will use data from aims #1-3 to assess the
 cost-effectiveness of iNO in ventilated premature infants.

 We are achieving these aims by augmenting the NHLBI iNO RCT data collection with: i.)
 survival follow-up for an average of 4 1/2 years; ii.) comprehensive, standardized follow-up
 clinic visits at 1, 2, 3 and 4 1/2 years to assess clinical outcomes, childhood development,
 and family burden; iii.) structured telephone interviews with parents every 3 months in year
 1 and every 6 months thereafter for an average of 4½ years to assess chronic morbidity and
 post-discharge healthcare use; iv.) collection of detailed hospital bills for the primary
 hospitalization, and; v.) a comprehensive analysis plan.

 This study will allow us to determine the long-term consequences of iNO therapy in this
 condition, aiding clinicians, families, and policymakers and immediately affecting care of
 critically ill infants. By combining with the NHLBI iNO RCT, we take advantage of an
 important opportunity to gather prospective long-term outcome data in a randomized fashion.
 Our proposal will significantly increase the return on investment in the RCT through a
 greater understanding of the impact of iNO therapy from a societal perspective. Neonatal
 intensive care has changed dramatically in the last ten years. This study will also provide
 contemporary information on the long-term outcomes of prematurity-associated respiratory
 failure following modern management. Finally, our data will allow assessment of the
 robustness of early proxies for subsequent outcomes, key for future study design in this
 area.
Inclusion Criteria:

 -  Enrolled in "Inhaled NO for the Prevention of Chronic Lung Disease" trial
 (ClinicalTrials.gov Identifier: NCT00006401).

 Exclusion Criteria:

 -  Did not consent to extended follow-up.