This multicenter trial tests whether inhaled nitric oxide will reduce death or the need for oxygen at 36 weeks postmenstrual age in preterm infants with severe lung disease.

Condition	Treatment or Intervention	Phase
Respiratory Distress Syndrome Infant, Premature Sepsis Pneumonia Hypertension, Pulmonary	Drug: inhaled nitric oxide	Phase III

Further Study Details: 

Expected Total Enrollment:  440

This multicenter, randomized, double-masked, controlled clinical trial evaluates the efficacy of inhaled nitric oxide (iNO) in the treatment of the preterm infant with respiratory failure secondary to respiratory distress syndrome (RDS), sepsis/pneumonia, aspiration syndrome, idiopathic pulmonary hypertension and/or suspected pulmonary hypoplasia. Infants are followed until death or discharge to home. The trial compares iNO therapy to mock gas delivery as the control and otherwise incorporates conventional management strategies (including treatment with surfactant and high frequency ventilation as adjuncts to iNO therapy). During the initial dosing, iNO is started at 5 ppm and may be increased to 10 ppm. If the infant does not respond, study gas is discontinued. For infants who respond to study gas, a gradual weaning is initiated following a well-defined protocol. The total exposure to study gas may not exceed 336 hours (14 days). Infants are monitored for signs of toxicity. Medical and neurodevelopmental outcome of surviving infants will be assessed at 18 to 22 months corrected age by masked, certified examiners.

To demonstrate that the use of iNO is associated with a clinically significant reduction (from 75% to 60%) in the primary outcome variable (incidence of death or BPD during initial hospitalization) using a power of 0.90 and an alpha of 0.05 for a two-tailed test, a sample of 440 will be required (220 infants in each arm of the study).

Ages Eligible for Study:  up to  120 Hours,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

• Any infant with a birth weight 401 - 1500 grams and < 34 weeks gestational age with an OI (mean Paw x FiO2 x 100/PaO2) > 10 on two consecutive blood gases at least 30 minutes apart, but no more than 12 hours apart.

or

• Infants > 1500 grams and < 34 weeks gestational age will be entered in the Larger Preemie Pilot Study if they have an OI greater than or equal to 15 on two consecutive blood gases at least 30 minutes apart, but no more than 12 hours apart.
• Infants requiring assisted ventilation with a diagnosis of RDS/HMD, pneumonia and/or sepsis, aspiration syndrome, idiopathic pulmonary hypertension, or suspected pulmonary hypoplasia associated with PROM and/or oligohydramnios.
• Greater than or equal to 4 hours after one dose of surfactant.
• Less than or equal to 120 hours of age.
• All infants must have an indwelling arterial line.

Exclusion Criteria

• Any infant in whom a decision has been made not to provide full treatment (e.g. chromosomal anomalies or severe birth asphyxia).
• Known structural congenital heart disease, except patent ductus arteriosus and atrial-level shunts.
• Infants with any major abnormality involving the respiratory system such as congenital diaphragmatic hernia, tracheoesophageal fistula or cystic fibrosis.
• Any bleeding diathesis considered to be clinically significant or thrombocytopenia with platelet count < 50,000.
• Prior enrollment into a conflicting clinical trial such as the Neonatal Network Surfactant CPAP trial.Inclusion Criteria

Rosemary Higgins      301-496-5575    higginsr@mail.nih.gov

Alabama
      University of Alabama, Birmingham,  Alabama,  United States; Recruiting
California
      Stanford University, Stanford,  California,  United States; Recruiting
      University of California San Diego, San Diego,  California,  United States; Not yet recruiting
Connecticut
      Yale University, New Haven,  Connecticut,  United States; Recruiting
Florida
      University of Miami, Miami,  Florida,  United States; Recruiting
Georgia
      Emory University, Atlanta,  Georgia,  United States; Recruiting
Indiana
      University of Indiana, Indianapolis,  Indiana,  United States; Recruiting
Michigan
      Wayne State University, Detroit,  Michigan,  United States; Recruiting
New York
      University of Rochester, Rochester,  New York,  United States; Not yet recruiting
Ohio
      University of Cincinnati, Cincinnati,  Ohio,  United States; Recruiting
Rhode Island
      Brown University, Providence,  Rhode Island,  United States; Recruiting
Texas
      University of Texas Southwestern Medical Center, Dallas,  Texas,  United States; Recruiting
      University of Texas, Houston,  Texas,  United States; Recruiting

Study chairs or principal investigators

Krisa VanMeurs, MD,  Principal Investigator,  Stanford University   

Study ID Numbers:  NICHD-1011
Record last reviewed:  March 2003
Last Updated:  October 13, 2004
Record first received:  May 14, 2001
ClinicalTrials.gov Identifier:  NCT00016523
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08