To determine whether or not inhaled nitric oxide (NO) safely decreases the incidence of chronic lung disease in premature infants.

Condition	Treatment or Intervention	Phase
Lung Diseases Bronchopulmonary Dysplasia	Procedure: mechanical ventilation	Phase III

Further Study Details: 

BACKGROUND: Despite advances in medical, nursing, and respiratory care, chronic lung disease (CLD) inflicts up to 50 percent of the prematurely born infants. As a result, nearly 50,000 infants in the United States develop CLD. It is desirable to investigate therapies that decrease the incidence of CLD because it is associated with failure to thrive and developmental delay, and increased risk of pulmonary infection, reactive airway disease, pulmonary hypertension, and death.

DESIGN NARRATIVE: Randomized, double-blind, placebo-controlled, and multi-centered. Three specific hypotheses are tested: that inhaled nitric oxide reduces the incidence of chronic lung disease, that inhaled nitric oxide reduces serum and lung (tracheal aspirate) markers of inflammation, and that inhaled nitric oxide does not increase the incidence of intraventricular hemorrhage in premature neonates. The primary endpoint is survival without chronic lung disease (defined as continued oxygen requirement) at 36 weeks post conceptional age.

A total of 800 premature newborns will be enrolled from 14 centers within 48 hours of life and be randomized to receive either placebo or inhaled nitric oxide (iNO) at 5 ppm until extubation or 21 days. The randomization will be performed using random blocks of 2 or 4 babies within each center by 3 gestational age strata (500-749 grams, 750-999 grams, and 1000-1250 grams). The iNO will be delivered by an INOvent delivery system which will be shrouded so that treating physicians and nurses will be unaware of the treatment group. Management strategies for aspects of patient care including mechanical ventilation, surfactant administration, fluid administration and steroid use will be determined by each center. Serial cranial ultrasounds and methemoglobin levels will be monitored to determine adverse events. The first 200 patients will also have serial blood samples and tracheal aspirates obtained for measurements of inflammatory mediators including interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), endothelin-1, myeloperoxidase and neutrophil counts (tracheal aspirates) and endothelin-1 (blood). To determine the incidence of long-term cardiopulmonary or neurologic sequelae, patients will be seen at 12 and 24 months of age. At these assessments a health questionnaire will be administered and Bayley II scales of infant development will be completed.

Ages Eligible for Study:  up to  1 Year,  Genders Eligible for Study:  Both

Criteria

Eligibility Inclusion Criteria: -500-1250 grams birth weight and gestational age < 34 weeks -Less than 48 hours old -Respiratory Failure on mechanical ventilation -Absence of structural heart disease (except PDA, ASD<1cm, or VSD<2mm if known prior to randomization) -Absence of lethal congenital anomaly Exclusion Criteria: -Participating in another concurrent experimental study (observational studies will be allowed with prior approval by the Steering Committee and Data and Safety Monitoring Board) -Active Pulmonary Hemorrhage -Unevacuated Pneumothorax -High frequency jet ventilation -Expected short duration of ventilation (< 48 hours from birth)

Arizona
      St. Joseph's Hospital, Phoenix,  Arizona,  85013,  United States; Recruiting
California
      Loma Linda U. Medical Center, Loma Linda,  California,  92350,  United States; Recruiting
      USC/Good Samaritan Hospital, Los Angeles,  California,  90033,  United States; Recruiting
Colorado
      Children's Hospital, Denver,  Colorado,  80218-1088,  United States; Recruiting
Connecticut
      Univ. of Connecticut Health Center, Farmington,  Connecticut,  06030,  United States; Recruiting
Iowa
      Univ. of Iowa Hosp. & Clinics, Iowa City,  Iowa,  52242,  United States; Recruiting
North Carolina
      Duke Univ. Medical Center, Durham,  North Carolina,  27710,  United States; Recruiting
      Univ. of North Carolina Chapel Hill, Chapel Hill,  North Carolina,  27599,  United States; Recruiting
Oklahoma
      Children's Hospital of Okla, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Pennsylvania
      Magee-Women's Hospital, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
      Pennsylvania Hospital, Philadelphia,  Pennsylvania,  19107,  United States; Recruiting
South Carolina
      Medical University of So. Carolina, Charleston,  South Carolina,  29425,  United States; Recruiting
Tennessee
      Vanderbilt Univ. Med. Center, Nashville,  Tennessee,  37232,  United States; Recruiting
Utah
      Utah Valley Regional Med. Ctr., Provo,  Utah,  84604,  United States; Recruiting

Study chairs or principal investigators

John Kinsella,  Children's Hospital   

Study ID Numbers:  135
Record last reviewed:  March 2005
Last Updated:  March 17, 2005
Record first received:  October 12, 2000
ClinicalTrials.gov Identifier:  NCT00006401
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08