Safety and Efficacy Study of Nitric Oxide for Inhalation on Chronic Lung Disease in Premature Babies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00551642
Recruitment Status : Completed
First Posted : October 31, 2007
Results First Posted : October 18, 2010
Last Update Posted : December 21, 2016
Information provided by (Responsible Party):

Brief Summary:
The purpose of this study is to assess the safety and efficacy of inhaled nitric oxide to reduce the risk of chronic lung disease in pre-term infants with respiratory distress, and to assess the long-term effects of the therapy on the development of these children over 7 years of clinical follow-up.

Condition or disease Intervention/treatment Phase
Lung Disease Drug: Nitric Oxide for inhalation Drug: Nitrogen Phase 3

Detailed Description:
Although the effects of inhaled Nitric Oxide on pulmonary vascular tone are well-described and relevant to term infants with persistent pulmonary hypertension, the pathophysiology of respiratory failure in preterm infants may be quite different. Chronic lung disease (CLD) represents the final pathway of a heterogeneous group of pulmonary disorders of infancy that usually start in the neonatal period. CLD most commonly occurs in preterm (<30 weeks of gestational age (GA) infants with birth weights less than 1,500 g, and especially in those very preterm (<26 wks GA) with birth weights less than 1,000 g, and who have been treated for respiratory distress syndrome (RDS).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 800 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: The Effects of Nitric Oxide for Inhalation on the Development of Chronic Lung Disease in Pre-term Infants
Study Start Date : May 2005
Actual Primary Completion Date : February 2008
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Diseases
U.S. FDA Resources

Arm Intervention/treatment
Group A
24+0-25+6 days weeks gestational age
Drug: Nitric Oxide for inhalation
inhaled nitric oxide given at 5 parts per million (ppm) for 7-21 days
Other Name: INOmax®
Drug: Nitrogen
nitrogen gas given at 5ppm for 7-21 days
Group B
26+0 - 28+6 days weeks Gestational Age
Drug: Nitric Oxide for inhalation
inhaled nitric oxide given at 5 parts per million (ppm) for 7-21 days
Other Name: INOmax®
Drug: Nitrogen
nitrogen gas given at 5ppm for 7-21 days

Primary Outcome Measures :
  1. Survival Without Bronchopulmonary Dysplasia (BPD) in Preterm Infants With Respiratory Distress [ Time Frame: 36 weeks gestational age ]
    The primary outcome was determined by assessment of survival and incidence of BPD,which was defined by the need for supplemental oxygen at 36 weeks gestational age (GA); an infant who was alive without BPD at 36 weeks GA was counted as success; an infant who died or had BPD at 36 weeks GA was counted as a failure.

  2. Survival [ Time Frame: 36 Weeks GA ]

Secondary Outcome Measures :
  1. Vital Signs [ Time Frame: Study Duration ]
  2. Arterial Oxygen Saturation by Pulse Oximetry [ Time Frame: Study Duration ]
  3. Adverse Events [ Time Frame: Study Duration ]
  4. Methemoglobin Level [ Time Frame: Baseline, then 24 hours, 2-6 days, Day 7 and Day 14 of treatment ]

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Ages Eligible for Study:   up to 26 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Inborn preterm infants 24+0 weeks-28+6 days weeks gestational age (defined by first trimester ultrasound or if not available based on the last menstrual period) who requires the use of surfactant within 24 hours of birth (either prophylactically, or for signs of developing respiratory distress), or who requires the use of continuous positive airway pressure (CPAP) (fraction of inspired oxygen concentration (FiO2) ≥ 0.30 on a mean airway pressure ≥ 4cm water (H2O)) within 24 hours of birth in order to maintain an oxygen saturation (SpO2) ≥ 85%.
  • Informed consent of the guardian.

Exclusion Criteria:

  • Outborn infants.
  • Infants ≥ 29 weeks gestational age.
  • Infants requiring FiO2 >0.5 to maintain SpO2 >85%, on a sufficient mean airway pressure (e.g., > 8 cm H2O on controlled mechanical ventilation (CMV)) in order to achieve adequate chest inflation (8-9 ribs on Chest X-ray) two hours after the proper administration of exogenous surfactant.
  • Any suspected congenital heart disease other than patent ductus arteriosus or atrial septal defect.
  • Any infant with severe bleeding or coagulation abnormalities at high-risk of diathesis, e.g., platelet <50,000/mm³, fibrinogen <0.5 g/L, other clotting factors <10%.
  • Any infant in whom a decision has been made not to provide full treatment, e.g., chromosomal abnormalities, severe multiple abnormalities, severe birth asphyxia, etc.
  • Use of another investigational drug or device before or during the active study period.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00551642

  Hide Study Locations
Bruxelles, Belgium
Clinique Notre Dame
Charleroi, Belgium
Universitair Ziekenhuis Antwerpen
Edegem, Belgium
Clinique St. Vincent CHC
Rocourt, Belgium
Oulun yliopsistollinen sairaala
Oulu, Finland, FI-90220
Centre Hospitalier Intercommunal de Creteil
Creteil, France, 94000
Hospital Mere-Enfant
Nantes Cedex 1, France, 44093
Hospital Robert Debre
Paris, France, 75019
Campus Charite Mitte
Berlin, Germany, 10117
Universitaetsklinikum Heidelberg
Heidelberg, Germany, 69115
Universitaetsklinikum Mannheim
Mannheim, Germany, 68167
Universitaetsklinikum Marburg
Marburg, Germany, 35033
Universitaetsklinikum Muenchen
Muenchen, Germany, 81377
Universitaeklinikum Tuebingen
Tuebingen, Germany, 72076
Univeritaetsklinik Ulm
Ulm, Germany, 89075
Az. Osp. G. Salesi
Ancona, Italy, 60123
Ospedali Riuniti
Bergamo, Italy, 24128
Policlinico S. Orsola
Bologna, Italy, 40138
Azienda Ospedaliera Careggi
Firenze, Italy, 50134
University Padova
Padova, Italy, 35128
Policlinico Gemelli
Roma, Italy, 00168
Beatrix Children's Hospital, University Medical Center Groningen
Groningen, Netherlands, 9713 GZ
Sophia Kinderziekenhuis
Rotterdam, Netherlands, 3000 CB
Hospital de Cruces
Barakaldo (Vizcaya), Spain, 48903
Hospital Universitario Vall d'Hebron
Barcelona, Spain, 08035
Hospital Universitario Gregorio Mar
Madrid, Spain, 28007
Hosspital Univeritario La Paz
Madrid, Spain, 28046
Hospital Universitario Canarias
Santa Cruz de Tenerife, Spain, 38320
Hospital Universitario Virgen del Rocio
Sevilla, Spain, 41013
Hospital Universitario La Fe
Valencia, Spain, 46009
Astrid Lindgrens barnsjukjus, Karolinska Unviersritets sjukhuset-Solna
Stockholm, Sweden, SE-171 76
Akademiska Sjukhuset
Uppsala, Sweden, SE-751 85
United Kingdom
Meedway Mariton Hospital
Kent, United Kingdom, ME7 5NY
Leicester Royal Infirmary
Leicester, United Kingdom, LE1 5WW
Kings College
London, United Kingdom, SE5 9RS
Sponsors and Collaborators
Study Chair: Jean-Christophe Mercier Hospital Robert Debre

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Mallinckrodt Identifier: NCT00551642     History of Changes
Other Study ID Numbers: INOT27
EUNO, EU Preemie
First Posted: October 31, 2007    Key Record Dates
Results First Posted: October 18, 2010
Last Update Posted: December 21, 2016
Last Verified: November 2016

Keywords provided by Mallinckrodt:
Preemie, Inhaled Nitric Oxide

Additional relevant MeSH terms:
Lung Diseases
Respiratory Tract Diseases
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Protective Agents