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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Mallinckrodt Identifier:
First received: October 30, 2007
Last updated: May 5, 2015
Last verified: May 2015
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 Intervention Phase
Lung Disease
Drug: Nitric Oxide for inhalation
Drug: Nitrogen
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: The Effects of Nitric Oxide for Inhalation on the Development of Chronic Lung Disease in Pre-term Infants

Resource links provided by NLM:

Further study details as provided by Mallinckrodt:

Primary Outcome Measures:
  • Survival Without Bronchopulmonary Dysplasia (BPD) in Preterm Infants With Respiratory Distress [ Time Frame: 36 weeks gestational age ] [ Designated as safety issue: No ]
    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.

  • Survival [ Time Frame: 36 Weeks GA ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Vital Signs [ Time Frame: Study Duration ] [ Designated as safety issue: Yes ]
  • Arterial Oxygen Saturation by Pulse Oximetry [ Time Frame: Study Duration ] [ Designated as safety issue: Yes ]
  • Adverse Events [ Time Frame: Study Duration ] [ Designated as safety issue: Yes ]
  • Methemoglobin Level [ Time Frame: Baseline, then 24 hours, 2-6 days, Day 7 and Day 14 of treatment ] [ Designated as safety issue: Yes ]

Enrollment: 800
Study Start Date: May 2005
Estimated Study Completion Date: June 2015
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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).

Ages Eligible for Study:   up to 26 Hours
Genders Eligible for Study:   Both
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.
  Contacts and Locations
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Please refer to this study by its identifier: 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
  More Information

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 
Study First Received: October 30, 2007
Results First Received: September 3, 2010
Last Updated: May 5, 2015
Health Authority: European Union: European Medicines Agency

Keywords provided by Mallinckrodt:
Preemie, Inhaled Nitric Oxide

Additional relevant MeSH terms:
Lung Diseases
Respiratory Tract Diseases
Nitric Oxide
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Endothelium-Dependent Relaxing Factors
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Vasodilator Agents processed this record on May 26, 2016