Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

420 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-01-31

Study Completion Date

2006-05-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Infant, Newborn Infant, Low Birth Weight Infant, Small for Gestational Age Infant, Premature Respiratory Distress Syndrome (RDS) Sepsis Pneumonia Hypertension, Pulmonary

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Inhaled Nitric Oxide

Group Type EXPERIMENTAL

Inhaled nitric oxide

Intervention Type DRUG

Started at 5 ppm and could be increased to 10 ppm

Placebo

Inhaled Oxygen

Group Type ACTIVE_COMPARATOR

Placebo

Intervention Type DRUG

Started at 5 ppm and could be increased to 10 ppm

Interventions

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Inhaled nitric oxide

Started at 5 ppm and could be increased to 10 ppm

Intervention Type DRUG

Placebo

Started at 5 ppm and could be increased to 10 ppm

Intervention Type DRUG

Eligibility Criteria

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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.

Maximum Eligible Age

120 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Stanford University

Principal Investigators

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Krisa P. Van Meurs, MD

Role: STUDY_DIRECTOR

Stanford University

Waldemar A. Carlo, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Abbot R. Laptook, MD

Role: PRINCIPAL_INVESTIGATOR

Brown University, Women & Infants Hospital of Rhode Island

Edward F. Donovan, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

James A. Lemons, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Shahnaz Duara, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Charles R. Rosenfeld, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas, Southwestern Medical Center at Dallas

Jon E. Tyson, MD MPH

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Seetha Shankaran, MD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Richard A. Ehrenkranz, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

T. Michael O'Shea, MD MPH

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University

Neil N. Finer, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Dale L. Phelps, MD

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Mark L. Hudak, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Robin H. Steinhorn, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

G. Ganesh Konduri, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin, Milwaukee

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

University of California at San Diego

San Diego, California, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

University of Florida

Jacksonville, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Wake Forest University

Charlotte, North Carolina, United States

Site Status

RTI International

Durham, North Carolina, United States

Site Status

Cincinnati Children's Medical Center

Cincinnati, Ohio, United States

Site Status

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, United States

Site Status

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Site Status

University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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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. doi: 10.1016/s0146-0005(03)00043-0.

Reference Type BACKGROUND

PMID: 14510322 (View on PubMed)

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. doi: 10.1056/NEJMoa043927.

Reference Type RESULT

PMID: 16000352 (View on PubMed)

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. doi: 10.1038/sj.jp.7211690. Epub 2007 Apr 19.

Reference Type RESULT

PMID: 17443204 (View on PubMed)

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. doi: 10.1016/j.jpeds.2007.02.012.

Reference Type RESULT

PMID: 17517240 (View on PubMed)

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. doi: 10.1016/j.jpeds.2007.03.017.

Reference Type RESULT

PMID: 17586184 (View on PubMed)

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. doi: 10.1038/jp.2008.18. Epub 2008 Mar 13.

Reference Type RESULT

PMID: 18337740 (View on PubMed)

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. doi: 10.1055/s-0028-1104743. Epub 2008 Dec 9.

Reference Type RESULT

PMID: 19067285 (View on PubMed)