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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00005776
Other study ID # NICHD-NRN-0014
Secondary ID U01HD019897U10HD
Status Terminated
Phase Phase 3
First received June 1, 2000
Last updated September 22, 2017
Start date October 1995
Est. completion date May 1998

Study information

Verified date September 2017
Source NICHD Neonatal Research Network
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Respiratory failure in term newborns is associated with increased rates of death and long-term neurodevelopmental problems. This large international multicenter trial randomized newborns who had failed to respond to intensive care, including high levels of ventilator support, to receive either inhaled nitric oxide (iNO) or 100 percent oxygen to test whether iNO would decrease their risk of dying or requiring temporary lung bypass. Infants were followed during their initial hospitalization; their outcome was assessed at 18 to 24 mos of age.


Description:

Respiratory failure in term newborns is associated with significant morbidity and mortality, despite maximal conventional therapy. Neonates with pulmonary hypertension have been treated with iNO, a selective pulmonary vasodilator. This multicenter, double-masked placebo-controlled randomized trial tested whether iNO would reduce the risk of death and/or the initiation of extracorporeal membrane oxygenation (ECMO) in a prospectively defined cohort of term or near-term neonates with hypoxic respiratory failure unresponsive to conventional therapy. The sample size was based on a reduction of the primary event (death or ECMO) from 50 percent to 30 percent; 90 percent power; and a two-tailed Type I error of 0.05.

Infants were evaluated at baseline for pulmonary, cardiac, bleeding status, and therapies received. Those who were greater than 34 wks gestation and 14 days old or less and required assisted ventilation with an OI (mean airway pressure x FiO2 divided by the PaO2 x 100) greater than 25 were eligible. They were randomly assigned to receive iNO at 20 ppm or 100 percent oxygen as a control. Infants whose PaO2 increased by less than 20 mm Hg after 30 minutes were studied at 80ppm iNO or control gas.; MetHg and NO2 concentrations were monitored regularly. Management, including surfactant administration, included prospectively defined criteria for study gas response, escalation, reinitiation, and weaning. The maximum total time on study gas was 336 hrs (after 240 hrs, the INO concentration was required to be no more than 5 ppm). Patients were followed to death, discharge, or 120 days and evaluated at 18-24 mos by a masked certified examiner.


Recruitment information / eligibility

Status Terminated
Enrollment 235
Est. completion date May 1998
Est. primary completion date May 1996
Accepts healthy volunteers No
Gender All
Age group N/A to 14 Days
Eligibility Inclusion Criteria:

- Greater than 34 wks gestational age

- One or more of the following diagnoses: primary pulmonary hypertension of the newborn, respiratory distress syndrome, perinatal aspiration syndrome, pneumonia/sepsis, suspected pulmonary hypoplasia

- Oxygenation Index (OI) greater than 15 and less than 25 on 2 arterial blood gases at least 15 min apart

- Indwelling arterial line

- Echocardiography before randomization

- Parental consent

Exclusion Criteria:

- Congenital diaphragmatic hernia

- Known congenital heart disease

- Decision not to provide full therapy

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Inhaled nitric oxide
Inhaled Nitric oxide at a concentration of 20 ppm
Placebo
100% Oxygen

Locations

Country Name City State
Canada Foothills Hospital Calgary Alberta
Canada Royal Alexandra Hospital Edmonton Alberta
Canada McMaster University Hamilton Ontario
Canada Montreal Children's Hospital Montreal Quebec
Canada Children's Hospital of Eastern Ontario Ottawa Ontario
Canada Royal University Hospital Saskatoon Saskatchewan
Canada Université de Sherbrooke, Sherbrooke, Quebec
Canada British Columbia Children's Hospital Vancouver British Columbia
Canada Health Sciences Center Winnipeg Manitoba
United States University of New Mexico Albuquerque New Mexico
United States Cincinnati Children's Medical Center Cincinnati Ohio
United States Case Western Reserve University, Rainbow Babies and Children's Hospital Cleveland Ohio
United States Wayne State University Detroit Michigan
United States Texas Children's Hospital Houston Texas
United States Indiana University Indianapolis Indiana
United States University of Tennessee Memphis Tennessee
United States Yale University New Haven Connecticut
United States Stanford University Palo Alto California
United States Brown University, Women & Infants Hospital of Rhode Island Providence Rhode Island
United States George Washington University Washington, D.C. District of Columbia

Sponsors (3)

Lead Sponsor Collaborator
NICHD Neonatal Research Network Medical Research Council of Canada, National Center for Research Resources (NCRR)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (5)

Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia. The Neonatal Inhaled Nitric Oxide Study Group (NINOS). Pediatrics. 1997 Jun;99(6):838-45. — View Citation

Inhaled nitric oxide in term and near-term infants: neurodevelopmental follow-up of the neonatal inhaled nitric oxide study group (NINOS). J Pediatr. 2000 May;136(5):611-7. — View Citation

Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med. 1997 Feb 27;336(9):597-604. Erratum in: N Engl J Med 1997 Aug 7;337(6):434. — View Citation

Sokol GM, Ehrenkranz RA. Inhaled nitric oxide therapy in neonatal hypoxic respiratory failure: insights beyond primary outcomes. Semin Perinatol. 2003 Aug;27(4):311-9. Review. — View Citation

Sokol GM, Fineberg NS, Wright LL, Ehrenkranz RA. Changes in arterial oxygen tension when weaning neonates from inhaled nitric oxide. Pediatr Pulmonol. 2001 Jul;32(1):14-9. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Death or initiation of ECMO Before hospital discharge or 120 days of life
Secondary PaO2 levels, oxygenation index, and alveolar-arterial oxygen gradient 30 minutes after drug administration
Secondary Neurodevelopmental outcome 18-22 Months Corrected Age
Secondary Duration of hospital stay At hospital discharge
Secondary Duration of assisted ventilation, air leaks, or chronic lung disease At hospital discharge
Secondary Transfers for ECMO At hospital discharge
Secondary Meeting ECMO criteria At hospital discharge
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