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

Sponsor

NICHD Neonatal Research Network (Other)

Overall Status

Terminated

CT.gov ID

NCT00016523

Collaborator

National Center for Research Resources (NCRR) (NIH)

420

Enrollment

Locations

Arms

63.9

Duration (Months)

24.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

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 :

Jan 1, 2001

Actual Primary Completion Date :

Sep 1, 2003

Actual Study Completion Date :

May 1, 2006

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Death or Bronchopulmonary Dysplasia [At 36 weeks post-conceptional age]

Secondary Outcome Measures

Intraventricular Hemorrhage Grade III and IV [At 36 weeks post-conceptional age]
Days on assisted ventilation [At 36 weeks post-conceptional age]
Length of hospitalization [At hospital discharge]
Retinopathy of prematurity [At hospital discharge]
Air leaks [At 36 weeks post-conceptual age]
Days on oxygen [At 36 weeks post-conceptual age]
Supplemental oxygen [At 36 weeks post-conceptual age]
Neurodevelopmental outcome [18-22 months corrected age]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 120 Hours

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Stanford University	Palo Alto	California	United States	94304
3	University of California at San Diego	San Diego	California	United States	92103-8774
4	Yale University	New Haven	Connecticut	United States	06504
5	University of Florida	Jacksonville	Florida	United States	32209
6	University of Miami	Miami	Florida	United States	33136
7	Northwestern University	Chicago	Illinois	United States	60614
8	Indiana University	Indianapolis	Indiana	United States	46202
9	Wayne State University	Detroit	Michigan	United States	48201
10	University of Rochester	Rochester	New York	United States	14642
11	Wake Forest University	Charlotte	North Carolina	United States	27157
12	RTI International	Durham	North Carolina	United States	27705
13	Cincinnati Children's Medical Center	Cincinnati	Ohio	United States	45267
14	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905
15	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75235
16	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030
17	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

NICHD Neonatal Research Network
National Center for Research Resources (NCRR)

Investigators

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