Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure

NCT00016523 | Terminated Phase 3 DMC

• 23 other identifiers: NICHD-NRN-0026U10HD034216M01RR000032U10HD027904U10HD027853M01RR008084U10HD027856M01RR000750U10HD021397M01RR016587U10HD027880M01RR000070U10HD040689M01RR000633U10HD021373U10HD021385U10HD027871M01RR006022U10HD040498M01RR007122U10HD040461U10HD040521M01RR000044
• Study Type: interventional
• Target: 420
• Locations: 1 country
• Sites: 17

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Death or Bronchopulmonary Dysplasia

  At 36 weeks post-conceptional age

Secondary Outcomes (8)

• 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

Study Arms (2)

Inhaled Nitric Oxide

EXPERIMENTAL

Inhaled Nitric Oxide

Drug: Inhaled nitric oxide

Placebo

ACTIVE COMPARATOR

Inhaled Oxygen

Drug: Placebo

Interventions

Inhaled nitric oxide DRUG

Started at 5 ppm and could be increased to 10 ppm

Inhaled Nitric Oxide

Placebo DRUG

Started at 5 ppm and could be increased to 10 ppm

Placebo

Eligibility Criteria

• Age: Up to 120 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• NICHD Neonatal Research Network: lead
• National Center for Research Resources (NCRR): collaborator

Study Sites (17)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

University of California at San Diego

San Diego, California, 92103-8774, United States

Location

Yale University

New Haven, Connecticut, 06504, United States

Location

University of Florida

Jacksonville, Florida, 32209, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Northwestern University

Chicago, Illinois, 60614, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Wake Forest University

Charlotte, North Carolina, 27157, United States

Location

RTI International

Durham, North Carolina, 27705, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45267, United States

Location

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (7)

• 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.

  PMID: 14510322 BACKGROUND

• 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.

  PMID: 16000352 RESULT

• 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.

  PMID: 17443204 RESULT

• 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.

  PMID: 17517240 RESULT

• 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.

  PMID: 17586184 RESULT

• 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.

  PMID: 18337740 RESULT

• 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.

  PMID: 19067285 RESULT

Related Links

• NICHD Neonatal Research Network

MeSH Terms

Conditions

Premature Birth; Respiratory Distress Syndrome; Sepsis; Pneumonia; Hypertension, Pulmonary; Familial Primary Pulmonary Hypertension

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Krisa P. Van Meurs, MD

  Stanford University

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: May 14, 2001
• First Posted: May 16, 2001
• Study Start: January 1, 2001
• Primary Completion: September 1, 2003
• Study Completion: May 1, 2006
• Last Updated: September 26, 2017

Record last verified: 2017-09

Locations

US (17)