Back to resultsInhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure (Preemie iNO)
Primary Purpose
Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age
Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Inhaled nitric oxide
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Infant, Newborn focused on measuring 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
Eligibility 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
Sites / Locations
- University of Alabama at Birmingham
- Stanford University
- University of California at San Diego
- Yale University
- University of Florida
- University of Miami
- Northwestern University
- Indiana University
- Wayne State University
- University of Rochester
- Wake Forest University
- RTI International
- Cincinnati Children's Medical Center
- Brown University, Women & Infants Hospital of Rhode Island
- University of Texas Southwestern Medical Center at Dallas
- University of Texas Health Science Center at Houston
- Medical College of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Inhaled Nitric Oxide
Placebo
Arm Description
Inhaled Nitric Oxide
Inhaled Oxygen
Outcomes
Primary Outcome Measures
Death or Bronchopulmonary Dysplasia
Secondary Outcome Measures
Intraventricular Hemorrhage Grade III and IV
Days on assisted ventilation
Length of hospitalization
Retinopathy of prematurity
Air leaks
Days on oxygen
Supplemental oxygen
Neurodevelopmental outcome
Full Information
NCT ID
NCT00016523
First Posted
May 14, 2001
Last Updated
September 22, 2017
Sponsor
NICHD Neonatal Research Network
Collaborators
National Center for Research Resources (NCRR)
1. Study Identification
Unique Protocol Identification Number
NCT00016523
Brief Title
Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure
Acronym
Preemie iNO
Official Title
Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Terminated
Why Stopped
Preliminary results showed increased intraventricular hemorrhage (IVH) in experimental arm
Study Start Date
January 2001 (undefined)
Primary Completion Date
September 2003 (Actual)
Study Completion Date
May 2006 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
NICHD Neonatal Research Network
Collaborators
National Center for Research Resources (NCRR)
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
420 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Inhaled Nitric Oxide
Arm Type
Experimental
Arm Description
Inhaled Nitric Oxide
Arm Title
Placebo
Arm Type
Active Comparator
Arm Description
Inhaled Oxygen
Intervention Type
Drug
Intervention Name(s)
Inhaled nitric oxide
Intervention Description
Started at 5 ppm and could be increased to 10 ppm
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Started at 5 ppm and could be increased to 10 ppm
Primary Outcome Measure Information:
Title
Death or Bronchopulmonary Dysplasia
Time Frame
At 36 weeks post-conceptional age
Secondary Outcome Measure Information:
Title
Intraventricular Hemorrhage Grade III and IV
Time Frame
At 36 weeks post-conceptional age
Title
Days on assisted ventilation
Time Frame
At 36 weeks post-conceptional age
Title
Length of hospitalization
Time Frame
At hospital discharge
Title
Retinopathy of prematurity
Time Frame
At hospital discharge
Title
Air leaks
Time Frame
At 36 weeks post-conceptual age
Title
Days on oxygen
Time Frame
At 36 weeks post-conceptual age
Title
Supplemental oxygen
Time Frame
At 36 weeks post-conceptual age
Title
Neurodevelopmental outcome
Time Frame
18-22 months corrected age
10. Eligibility
Sex
All
Maximum Age & Unit of Time
120 Hours
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Krisa P. Van Meurs, MD
Organizational Affiliation
Stanford University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Waldemar A. Carlo, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Abbot R. Laptook, MD
Organizational Affiliation
Brown University, Women & Infants Hospital of Rhode Island
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Edward F. Donovan, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
James A. Lemons, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Shahnaz Duara, MD
Organizational Affiliation
University of Miami
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Charles R. Rosenfeld, MD
Organizational Affiliation
University of Texas, Southwestern Medical Center at Dallas
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jon E. Tyson, MD MPH
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Seetha Shankaran, MD
Organizational Affiliation
Wayne State University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Richard A. Ehrenkranz, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
T. Michael O'Shea, MD MPH
Organizational Affiliation
Wake Forest University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Neil N. Finer, MD
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dale L. Phelps, MD
Organizational Affiliation
University of Rochester
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mark L. Hudak, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Robin H. Steinhorn, MD
Organizational Affiliation
Northwestern University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
G. Ganesh Konduri, MD
Organizational Affiliation
Medical College of Wisconsin, Milwaukee
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of California at San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92103-8774
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06504
Country
United States
Facility Name
University of Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Wake Forest University
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
RTI International
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Cincinnati Children's Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Brown University, Women & Infants Hospital of Rhode Island
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
University of Texas Southwestern Medical Center at Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
14510322
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. doi: 10.1016/s0146-0005(03)00043-0.
Results Reference
background
PubMed Identifier
16000352
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, 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.
Results Reference
result
PubMed Identifier
17443204
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. doi: 10.1038/sj.jp.7211690. Epub 2007 Apr 19.
Results Reference
result
PubMed Identifier
17517240
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 Jun;150(6):592-6, 596.e1-5. doi: 10.1016/j.jpeds.2007.02.012.
Results Reference
result
PubMed Identifier
17586184
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 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.
Results Reference
result
PubMed Identifier
18337740
Citation
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.
Results Reference
result
PubMed Identifier
19067285
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(4):317-22. doi: 10.1055/s-0028-1104743. Epub 2008 Dec 9.
Results Reference
result
Links:
URL
http://neonatal.rti.org
Description
NICHD Neonatal Research Network
Learn more about this trial
Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure
We'll reach out to this number within 24 hrs