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Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure (Preemie iNO)

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ClinicalTrials.gov Identifier: NCT00016523
Recruitment Status : Terminated (Preliminary results showed increased intraventricular hemorrhage (IVH) in experimental arm)
First Posted : May 16, 2001
Last Update Posted : September 26, 2017
National Center for Research Resources (NCRR)
Information provided by:
NICHD Neonatal Research Network

Brief Summary:
This multicenter trial tested whether inhaled nitric oxide would reduce death or the need for oxygen in preterm infants (less than 34 weeks gestational age) with severe lung disease.

Condition or disease Intervention/treatment Phase
Infant, Newborn Infant, Low Birth Weight Infant, Small for Gestational Age Infant, Premature Respiratory Distress Syndrome (RDS) Sepsis Pneumonia Hypertension, Pulmonary Drug: Inhaled nitric oxide Drug: Placebo Phase 3

Detailed Description:

This multicenter, randomized, double-masked, controlled clinical trial evaluated 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 were followed until death or discharge to home. The trial compared iNO therapy to mock gas delivery as the control, and otherwise incorporated conventional management strategies (including treatment with surfactant and high frequency ventilation as adjuncts to iNO therapy).

During the initial dosing, iNO was started at 5 ppm and could be increased to 10 ppm. If the infant did not respond, study gas was discontinued. For infants who responded to study gas, a gradual weaning was initiated. The total exposure to study gas did not exceed 336 hours (14 days). Infants were monitored for signs of toxicity.

Medical and neurodevelopmental outcome of surviving infants were assessed at 18 to 22 months corrected age by masked, certified examiners.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 420 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure
Study Start Date : January 2001
Actual Primary Completion Date : September 2003
Actual Study Completion Date : May 2006

Arm Intervention/treatment
Experimental: Inhaled Nitric Oxide
Inhaled Nitric Oxide
Drug: Inhaled nitric oxide
Started at 5 ppm and could be increased to 10 ppm

Active Comparator: Placebo
Inhaled Oxygen
Drug: Placebo
Started at 5 ppm and could be increased to 10 ppm

Primary Outcome Measures :
  1. Death or Bronchopulmonary Dysplasia [ Time Frame: At 36 weeks post-conceptional age ]

Secondary Outcome Measures :
  1. Intraventricular Hemorrhage Grade III and IV [ Time Frame: At 36 weeks post-conceptional age ]
  2. Days on assisted ventilation [ Time Frame: At 36 weeks post-conceptional age ]
  3. Length of hospitalization [ Time Frame: At hospital discharge ]
  4. Retinopathy of prematurity [ Time Frame: At hospital discharge ]
  5. Air leaks [ Time Frame: At 36 weeks post-conceptual age ]
  6. Days on oxygen [ Time Frame: At 36 weeks post-conceptual age ]
  7. Supplemental oxygen [ Time Frame: At 36 weeks post-conceptual age ]
  8. Neurodevelopmental outcome [ Time Frame: 18-22 months corrected age ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 120 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00016523

Show Show 17 study locations
Sponsors and Collaborators
NICHD Neonatal Research Network
National Center for Research Resources (NCRR)
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Study Director: Krisa P. Van Meurs, MD Stanford University
Principal Investigator: Waldemar A. Carlo, MD University of Alabama at Birmingham
Principal Investigator: Abbot R. Laptook, MD Brown University, Women & Infants Hospital of Rhode Island
Principal Investigator: Edward F. Donovan, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: James A. Lemons, MD Indiana University
Principal Investigator: Shahnaz Duara, MD University of Miami
Principal Investigator: Charles R. Rosenfeld, MD University of Texas, Southwestern Medical Center at Dallas
Principal Investigator: Jon E. Tyson, MD MPH The University of Texas Health Science Center, Houston
Principal Investigator: Seetha Shankaran, MD Wayne State University
Principal Investigator: Richard A. Ehrenkranz, MD Yale University
Principal Investigator: T. Michael O'Shea, MD MPH Wake Forest University
Principal Investigator: Neil N. Finer, MD University of California, San Diego
Principal Investigator: Dale L. Phelps, MD University of Rochester
Principal Investigator: Mark L. Hudak, MD University of Florida
Principal Investigator: Robin H. Steinhorn, MD Northwestern University
Principal Investigator: G. Ganesh Konduri, MD Medical College of Wisconsin, Milwaukee
Additional Information:
Publications of Results:

Other Publications:
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Responsible Party: Krisa P. Van Meurs, MD, Lead Principal Investigator, Stanford University
ClinicalTrials.gov Identifier: NCT00016523    
Other Study ID Numbers: NICHD-NRN-0026
U10HD034216 ( U.S. NIH Grant/Contract )
M01RR000032 ( U.S. NIH Grant/Contract )
U10HD027904 ( U.S. NIH Grant/Contract )
U10HD027853 ( U.S. NIH Grant/Contract )
M01RR008084 ( U.S. NIH Grant/Contract )
U10HD027856 ( U.S. NIH Grant/Contract )
M01RR000750 ( U.S. NIH Grant/Contract )
U10HD021397 ( U.S. NIH Grant/Contract )
M01RR016587 ( U.S. NIH Grant/Contract )
U10HD027880 ( U.S. NIH Grant/Contract )
M01RR000070 ( U.S. NIH Grant/Contract )
U10HD040689 ( U.S. NIH Grant/Contract )
M01RR000633 ( U.S. NIH Grant/Contract )
U10HD021373 ( U.S. NIH Grant/Contract )
U10HD021385 ( U.S. NIH Grant/Contract )
U10HD027871 ( U.S. NIH Grant/Contract )
M01RR006022 ( U.S. NIH Grant/Contract )
U10HD040498 ( U.S. NIH Grant/Contract )
M01RR007122 ( U.S. NIH Grant/Contract )
U10HD040461 ( U.S. NIH Grant/Contract )
U10HD040521 ( U.S. NIH Grant/Contract )
M01RR000044 ( U.S. NIH Grant/Contract )
First Posted: May 16, 2001    Key Record Dates
Last Update Posted: September 26, 2017
Last Verified: September 2017
Keywords provided by NICHD Neonatal Research Network:
NICHD Neonatal Research Network
Extremely Low Birth Weight (ELBW)
Very Low Birth Weight (VLBW)
Inhaled nitric oxide
Aspiration syndrome
Idiopathic pulmonary hypertension
Pulmonary hypoplasia
Additional relevant MeSH terms:
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Respiratory Distress Syndrome
Respiratory Distress Syndrome, Newborn
Respiratory Insufficiency
Hypertension, Pulmonary
Birth Weight
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Body Weight
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Protective Agents