Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure - Full Text View

Sponsor:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborator:	National Center for Research Resources (NCRR)
Information provided by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00016523

Purpose

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	Intervention	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 III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure

Resource links provided by NLM:

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: High Blood Pressure Oxygen Therapy Pneumonia Premature Babies Pulmonary Hypertension Sepsis

Drug Information available for: Nitric oxide

U.S. FDA Resources

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:

Death or Bronchopulmonary Dysplasia [ Time Frame: At 36 weeks post-conceptional age ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Intraventricular Hemorrhage Grade III and IV [ Time Frame: At 36 weeks post-conceptional age ] [ Designated as safety issue: Yes ]
Days on assisted ventilation [ Time Frame: At 36 weeks post-conceptional age ] [ Designated as safety issue: No ]
Length of hospitalization [ Time Frame: At hospital discharge ] [ Designated as safety issue: No ]
Retinopathy of prematurity [ Time Frame: At hospital discharge ] [ Designated as safety issue: Yes ]
Air leaks [ Time Frame: At 36 weeks post-conceptual age ] [ Designated as safety issue: Yes ]
Days on oxygen [ Time Frame: At 36 weeks post-conceptual age ] [ Designated as safety issue: No ]
Supplemental oxygen [ Time Frame: At 36 weeks post-conceptual age ] [ Designated as safety issue: No ]
Neurodevelopmental outcome [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: No ]

Enrollment:	420
Study Start Date:	January 2001
Study Completion Date:	May 2006
Primary Completion Date:	September 2003 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility

Ages Eligible for Study:	up to 120 Hours
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00016523

Locations

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, California
Stanford University
Palo Alto, California, United States, 94304
University of California at San Diego
San Diego, California, United States, 92103-8774
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06504
United States, Florida
University of Florida
Jacksonville, Florida, United States, 32209
University of Miami
Miami, Florida, United States, 33136
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60614
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, New York
University of Rochester
Rochester, New York, United States, 14642
United States, North Carolina
Wake Forest University
Charlotte, North Carolina, United States, 27157
RTI International
Durham, North Carolina, United States, 27705
United States, Ohio
Cincinnati Children's Medical Center
Cincinnati, Ohio, United States, 45267
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States, 02905
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75235
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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, Jacksonville
Principal Investigator:	Robin H. Steinhorn, MD	Northwestern University
Principal Investigator:	G. Ganesh Konduri, MD	Medical College of Wisconsin, Milwaukee

More Information

Additional Information:

NICHD Neonatal Research Network This link exits the ClinicalTrials.gov site

Cochrane meta-analyses: "Inhaled nitric oxide for respiratory failure in preterm infants" This link exits the ClinicalTrials.gov site

NICHD Pregnancy & Perinatology Branch This link exits the ClinicalTrials.gov site

Publications:

Van Meurs KP, Wright LL, Ehrenkranz RA, Lemons JA, Ball MB, Poole WK, Perritt R, Higgins RD, Oh W, Hudak ML, Laptook AR, Shankaran S, Finer NN, Carlo WA, Kennedy KA, Fridriksson JH, Steinhorn RH, Sokol GM, Konduri GG, Aschner JL, Stoll BJ, D'Angio CT, Stevenson DK; Preemie Inhaled Nitric Oxide Study. Inhaled nitric oxide for premature infants with severe respiratory failure. N Engl J Med. 2005 Jul 7;353(1):13-22.

Van Meurs KP, Hintz SR, Ehrenkranz RA, Lemons JA, Ball MB, Poole WK, Perritt R, Das A, Higgins RD, Stevenson DK. Inhaled nitric oxide in infants >1500 g and <34 weeks gestation with severe respiratory failure. J Perinatol. 2007 Jun;27(6):347-52. Epub 2007 Apr 19.

Hintz SR, Slovis T, Bulas D, Van Meurs KP, Perritt R, Stevenson DK, Poole WK, Das A, Higgins RD; NICHD Neonatal Research Network. Interobserver reliability and accuracy of cranial ultrasound scanning interpretation in premature infants. J Pediatr. 2007 Jun;150(6):592-6, 596.e1-5.

Hintz SR, Van Meurs KP, Perritt R, Poole WK, Das A, Stevenson DK, Ehrenkranz RA, Lemons JA, Vohr BR, Heyne R, Childers DO, Peralta-Carcelen M, Dusick A, Johnson YR, Morris B, Dillard R, Vaucher Y, Steichen J, Adams-Chapman I, Konduri G, Myers GJ, de Ungria M, Tyson JE, Higgins RD; NICHD Neonatal Research Network. Neurodevelopmental outcomes of premature infants with severe respiratory failure enrolled in a randomized controlled trial of inhaled nitric oxide. J Pediatr. 2007 Jul;151(1):16-22, 22.e1-3.

Ambalavanan N, Van Meurs KP, Perritt R, Carlo WA, Ehrenkranz RA, Stevenson DK, Lemons JA, Poole WK, Higgins RD; NICHD Neonatal Research Network, Bethesda, MD. Predictors of death or bronchopulmonary dysplasia in preterm infants with respiratory failure. J Perinatol. 2008 Jun;28(6):420-6. Epub 2008 Mar 13.

Chock VY, Van Meurs KP, Hintz SR, Ehrenkranz RA, Lemons JA, Kendrick DE, Stevenson DK; NICHD Neonatal Research Network. Inhaled nitric oxide for preterm premature rupture of membranes, oligohydramnios, and pulmonary hypoplasia. Am J Perinatol. 2009 Apr;26(4):317-22. Epub 2008 Dec 9.

Sokol GM, Ehrenkranz RA. Inhaled nitric oxide therapy in neonatal hypoxic respiratory failure: insights beyond primary outcomes. Semin Perinatol. 2003 Aug;27(4):311-9. Review.

Responsible Party:	Krisa P. Van Meurs, MD, Lead Principal Investigator, Stanford University
ClinicalTrials.gov Identifier:	NCT00016523 History of Changes
Other Study ID Numbers:	NICHD-NRN-0026, U10HD034216, M01RR000032, U10HD027904, U10HD027853, M01RR008084, U10HD027856, M01RR000750, U10HD021397, M01RR016587, U10HD027880, M01RR000070, U10HD040689, M01RR000633, U10HD021373, U10HD021385, U10HD027871, M01RR006022, U10HD040498, M01RR007122, U10HD040461, U10HD040521, M01RR000044
Study First Received:	May 14, 2001
Last Updated:	January 10, 2011
Health Authority:	United States: Federal Government; United States: Institutional Review Board; United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

NICHD Neonatal Research Network
Extremely Low Birth Weight (ELBW)
Very Low Birth Weight (VLBW)
Prematurity

Inhaled nitric oxide
Aspiration syndrome
Idiopathic pulmonary hypertension
Pulmonary hypoplasia

Additional relevant MeSH terms:

Birth Weight
Hypertension
Hypertension, Pulmonary
Pneumonia
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Sepsis
Respiratory Insufficiency
Body Weight
Signs and Symptoms
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections

Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on February 12, 2012