Inhaled Nitric Oxide and Neuroprotection in Premature Infants

NCT ID: NCT00515281

Last Updated: 2024-10-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 273 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2023-11-28

Brief Summary

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

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.

Conditions

Prematurity; Bronchopulmonary Dysplasia; Intraventricular Hemorrhage; Periventricular Leukomalacia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

INO Control (Short iNO)

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

Group Type: PLACEBO_COMPARATOR

inhaled nitric oxide

Intervention Type: DRUG

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.

INO Treatment (Long iNO)

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

Group Type: EXPERIMENTAL

inhaled nitric oxide

Intervention Type: DRUG

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.

oxygen

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

INO; O2

Eligibility Criteria

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

• Minimum Eligible Age: 2 Hours
• Maximum Eligible Age: 72 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael D. Schreiber, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

The University of Chicago

Chicago, Illinois, United States

Countries

United States

References

Schreiber MD, Gin-Mestan K, Marks JD, Huo D, Lee G, Srisuparp P. Inhaled nitric oxide in premature infants with the respiratory distress syndrome. N Engl J Med. 2003 Nov 27;349(22):2099-107. doi: 10.1056/NEJMoa031154.

Reference Type: BACKGROUND

PMID: 14645637 (View on PubMed)

Mestan KK, Marks JD, Hecox K, Huo D, Schreiber MD. Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide. N Engl J Med. 2005 Jul 7;353(1):23-32. doi: 10.1056/NEJMoa043514.

Reference Type: BACKGROUND

PMID: 16000353 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

15405A

Identifier Type: -

Identifier Source: org_study_id