NOVA2: Inhaled Nitric Oxide and Neuroprotection in Premature Infants

Sponsor

University of Chicago (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00515281

Collaborator

(none)

484

Enrollment

Location

Arms

157.2

Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether inhaled nitric oxide improves the neurological outcome for premature infants.

Condition or Disease	Intervention/Treatment	Phase
Prematurity Bronchopulmonary Dysplasia Intraventricular Hemorrhage Periventricular Leukomalacia	Drug: inhaled nitric oxide Drug: oxygen	Phase 2/Phase 3

Detailed Description

With the advances in modern neonatal intensive care medicine in the last 20 years, survival of extremely preterm infants weighing less than 1500g (< 3 lbs, 5 oz) has risen markedly. However, with this increased survival has come a marked increase in the number of infants with serious neurodevelopmental disabilities: Premature infants with birth weights less than 1500g who survive to go home are at significant risk for serious neurodevelopmental problems: cognitive and motor delays, blindness, deafness, and cerebral palsy. In a recent randomized, placebo-controlled clinical trial, we assessed whether giving mechanically ventilated preterm infants inhaled nitric oxide gas (iNO) for 1 week after birth decreased the incidence of death and chronic lung disease. An unanticipated outcome of that study (Schreiber et. al. 2003) and a subsequent study of those infants at 2 years of age (Mestan et. al. 2005) was that premature infants treated with inhaled nitric oxide (iNO) have improved neurodevelopmental outcomes and physical growth at 2 years corrected age, compared with placebo-treated infants (Mestan et. al. 2005). INO therapy, therefore, appears to be a new treatment to protect the premature brain during development outside the womb. The overall goal of this application is understand the efficacy of iNO treatment in improving neurodevelopmental outcomes in at-risk premature infants.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

484 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Inhaled Nitric Oxide and Neuroprotection in Premature Infants

Study Start Date :

May 1, 2008

Anticipated Primary Completion Date :

Jun 7, 2021

Anticipated Study Completion Date :

Jun 7, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INO Treatment The treatment group will receive iNO, combined with O2 or room air, until 33 weeks corrected age.	Drug: inhaled nitric oxide The amount of gas will be carefully controlled and adjusted to the level that best improves the function of subject's lungs. The subject will remain on inhaled nitric oxide until he/she reaches 33 weeks of gestation if assigned to the treatment arm, or until the 8th day of the study if he/she is assigned to the control arm. Other Names: INO
Placebo Comparator: INO Control INO will be given to infants in the control group for the first 7 days of the study gas, then O2 or room air, as clinically appropriate, on the 8th day, until 33 weeks corrected age	Drug: inhaled nitric oxide The amount of gas will be carefully controlled and adjusted to the level that best improves the function of subject's lungs. The subject will remain on inhaled nitric oxide until he/she reaches 33 weeks of gestation if assigned to the treatment arm, or until the 8th day of the study if he/she is assigned to the control arm. Other Names: INO Drug: oxygen The amount of gas will be carefully controlled and adjusted to the level that best improves the function of the subject's lungs. Subjects in the control arm of the study will receive oxygen beginning on the 8th day of the study until he/she reaches 33 weeks of gestation. Other Names: O2

Arm

Intervention/Treatment

Experimental: INO Treatment

The treatment group will receive iNO, combined with O2 or room air, until 33 weeks corrected age.

Drug: inhaled nitric oxide

The amount of gas will be carefully controlled and adjusted to the level that best improves the function of subject's lungs. The subject will remain on inhaled nitric oxide until he/she reaches 33 weeks of gestation if assigned to the treatment arm, or until the 8th day of the study if he/she is assigned to the control arm.

Other Names:

INO

Placebo Comparator: INO Control

INO will be given to infants in the control group for the first 7 days of the study gas, then O2 or room air, as clinically appropriate, on the 8th day, until 33 weeks corrected age

Drug: inhaled nitric oxide

Other Names:

INO

Drug: oxygen

The amount of gas will be carefully controlled and adjusted to the level that best improves the function of the subject's lungs. Subjects in the control arm of the study will receive oxygen beginning on the 8th day of the study until he/she reaches 33 weeks of gestation.

Other Names:

Outcome Measures

Primary Outcome Measures

Neurodevelopment [Two years]
Bronchopulmonary dysplasia [36 weeks of age corrected]

Secondary Outcome Measures

Severe IVH / PVL [40 weeks of age corrected]

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Hours to 72 Hours

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Prematurity (birthweight ≤ 1500g, < 31 weeks gestation)
Requiring respiratory support
Admitted to the NICU at the University of Chicago

Exclusion Criteria:

Severe congenital anomalies
Genetic syndromes
Extremely sick preterm infants requiring very high ventilatory pressures (OI ≥ 20)
Premature infants judged by the physician as nonviable