Inhaled nitric oxide reduces the risk of temporary lung bypass in term and near-term infants with severe respiratory failure. Term and near-term infants with mild to moderate respiratory failure on a ventilator are randomized to inhaled nitric oxide to 100 percent oxygen to determine if administration of inhaled nitric oxide earlier in their course or to infants with less severe respiratory failure decreases the incidence of death or ECMO. The neurodevelopment of infants will be evaluated at 18 to 24 months of age.

Condition	Treatment or Intervention	Phase
Hypertension, Pulmonary Respiratory Insufficiency Infant, Newborn, Diseases Meconium Aspiration Persistent Fetal Circulation Syndrome Pneumonia, Aspiration Respiratory Distress Syndrome	Drug: Inhaled Nitric Oxide	Phase III

Further Study Details: 

Expected Total Enrollment:  400

Respiratory failure occurs in near term and term infants as a complication of perinatal aspiration syndromes, pneumonia, sepsis, respiratory distress syndrome and primary pulmonary hypertension. Recently the collaborative trial of the NICHD Neonatal Research Network and the Canadian Inhaled Nitric Oxide Study Group (the NINOS trial) demonstrated that inhaled nitric oxide decreases the need for ECMO/death from 64 percent in the control group to 46 percent in term/near term infants with respiratory failure. The purpose of this study is to determine if administration of inhaled nitric oxide earlier in the course of respiratory failure and to infants with less severe respiratory failure, decreases the incidence of ECMO or death, as suggested by the sub-group analysis of the original NINOS trial. Infants are enrolled at gestational age greater than 34 weeks (near term and term). The study is prospective, randomized and double masked. The study will compare the outcome of infants received INO at OI greater than 15 and less than 25, with a control group that does not receive early INO. INO will be delivered at 20 ppm during the initial dose-response evaluation. Infants in either group who show subsequent deterioration with OI greater than 25 on two consecutive ABGs at least one hour apart or a rapid deterioration with OI greater than 30 on two consecutive ABGs 15 minutes apart receive open label INO therapy as part of standard medical management. Specific guidelines are followed for the use of high frequency ventilation and surfactant during study gas administration to prevent them from confounding the results of the study.

Secondary hypotheses include the following: early INO will reduce the probability of OI exceeding 25 on two consecutive blood gases drawn at least one hour apart or an OI greater than 30 on two consecutive ABGs 15 minutes apart; Early INO therapy will reduce the probability of OI exceeding 40 on 2 consecutive arterial blood gases done at least 30 minutes apart; there will be no difference in neurodevelopmental or hearing impairments evaluated at 18-24 months of corrected age between INO treated and control groups.

A sample size of 400 infants (200 each for placebo and INO arms) will be needed to detect an anticipated decrease in probability of death/initiation of ECMO from 35 percent in the control group to 20 percent in the INO group at 95 percent confidence level and with 90 percent power, using a two-tailed hypothesis.

Ages Eligible for Study:  up to  14 Days,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Greater than 34 weeks gestational age
• Require assisted ventilation for hypoxic respiratory failure
• One of the following diagnoses: primary persistent pulmonary hypertension (PPHN), respiratory distress syndrome, perinatal aspiration syndrome, pneumonia/sepsis, suspected pulmonary hypoplasia
• An oxygen index greater than 15 and less than 25 on 2 arterial blood gases at least 15 minutes apart on Fi02 greater than 80 percent
• Indwelling arterial line
• Parental consent

Exclusion Criteria:

• Known structural congenital heart disease, except patent ductus arteriosus and atrial level shunts
• Congenital diaphragmatic hernia
• Use of high frequency jet ventilation at the time of randomization
• Prior exposure to inhaled nitric oxide therapy

Alabama
      University of Alabama, Birmingham,  Alabama,  35294,  United States
Arizona
      St. Joseph's Hospital, Phoenix,  Arizona,  85013,  United States
California
      Stanford University, Palo Alto,  California,  94304,  United States
      San Diego Children's Hospital, San Diego,  California,  92130,  United States
Connecticut
      Yale University, New Haven,  Connecticut,  06520,  United States
Florida
      University of Miami, Miami,  Florida,  33101,  United States
Georgia
      Emory University, Atlanta,  Georgia,  30335,  United States
Indiana
      Indiana University, Indianapolis,  Indiana,  46202-4716,  United States
Michigan
      Wayne State University, Detroit,  Michigan,  48201,  United States
New Mexico
      University of New Mexico, Albuquerque,  New Mexico,  87131,  United States
Ohio
      Case Western Reserve University, Cleveland,  Ohio,  44106,  United States
      University of Cincinnati, Cincinnati,  Ohio,  45267-0541,  United States
Rhode Island
      Women and Infants, Providence,  Rhode Island,  02903,  United States
Tennessee
      University of Tennessee, Memphis,  Tennessee,  38163,  United States
Texas
      University of Texas, Dallas,  Texas,  75235,  United States
      University of Texas, Houston,  Texas,  United States
      Texas Children's Hospital, Houston,  Texas,  77030,  United States
Washington
      University of Washington School of Medicine, Seattle,  Washington,  98195,  United States

Study chairs or principal investigators

Ganesh Konduri,  Principal Investigator,  University of Wisconsin   

Study ID Numbers:  NICHD-1005; U10 HD21397; U10 HD27853; U10 HD27871; U10 HD21364; U10 HD21415; U10 HD27856; U10 HD27904; U10 HD27881; U10 HD21385; U10 HD27880; U10 HD21373; U10 HD34216
Record last reviewed:  February 2003
Last Updated:  October 13, 2004
Record first received:  June 1, 2000
ClinicalTrials.gov Identifier:  NCT00005773
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08