Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure

Sepsis Clinical Trial

— Preemie iNO  

Official title:

Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00016523
• Other study ID #: NICHD-NRN-0026
• Secondary ID: U10HD034216M01RR
• Status: Terminated
• Phase: Phase 3
• First received: May 14, 2001
• Last updated: September 22, 2017
• Start date: January 2001
• Est. completion date: May 2006

Study information

• Verified date: September 2017
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 420
• Est. completion date: May 2006
• Est. primary completion date: September 2003
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 120 Hours

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Inhaled nitric oxide
Started at 5 ppm and could be increased to 10 ppm
• Placebo
Started at 5 ppm and could be increased to 10 ppm

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Wake Forest University	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Cincinnati Children's Medical Center	Cincinnati	Ohio
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	RTI International	Durham	North Carolina
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Florida	Jacksonville	Florida
United States	University of Miami	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Yale University	New Haven	Connecticut
United States	Stanford University	Palo Alto	California
United States	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	University of Rochester	Rochester	New York
United States	University of California at San Diego	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

References & Publications (7)

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 — View Citation

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 — View Citation

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 Ju — View Citation

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 Ungri — View Citation

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. — View Citation

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 — View Citation

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, Ste — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death or Bronchopulmonary Dysplasia		At 36 weeks post-conceptional age
Secondary	Intraventricular Hemorrhage Grade III and IV		At 36 weeks post-conceptional age
Secondary	Days on assisted ventilation		At 36 weeks post-conceptional age
Secondary	Length of hospitalization		At hospital discharge
Secondary	Retinopathy of prematurity		At hospital discharge
Secondary	Air leaks		At 36 weeks post-conceptual age
Secondary	Days on oxygen		At 36 weeks post-conceptual age
Secondary	Supplemental oxygen		At 36 weeks post-conceptual age
Secondary	Neurodevelopmental outcome		18-22 months corrected age

External Links

•   NICHD Neonatal Research Network