Clinical trial NCT00551642: Safety and Efficacy Study of Nitric Oxide for Inhalation on Chronic Lung Disease in Premature Babies
Official title: The Effects of Nitric Oxide for Inhalation on the Development of Chronic Lung Disease in Pre-term Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Disease
Keywords: Preemie, Inhaled Nitric Oxide
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2007-10-31
Enrollment: 800
Sex: ALL
Maximum age (years): 26
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 grams (g), and especially in those very preterm (\<26 weeks GA) with birth weights less than 1,000 g, and who have been treated for respiratory distress syndrome (RDS).

Eligibility criteria: 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 per millimeter cube (mm³), fibrinogen \<0.5 gram per liter (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.

Primary outcomes:
measure: Survival Without Bronchopulmonary Dysplasia (BPD) in Preterm Infants With Respiratory Distress
timeFrame: 21 days
Secondary outcomes:
Other outcomes:
measure: Mortality at 7-year Follow-up
timeFrame: at 7-year Follow-up
measure: Strengths and Difficulties Questionnaire Results for Participants at 7-year Follow-up
timeFrame: At 7-year Follow-up
Locations:
city: Bruxelles
country: Belgium
facility: UCL St. LUC
city: Charleroi
country: Belgium
facility: Clinique Notre Dame
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Rocourt
country: Belgium
facility: Clinique St. Vincent CHC
city: Oulu
country: Finland
facility: Oulun yliopsistollinen sairaala
city: Creteil
country: France
facility: Centre Hospitalier Intercommunal de Creteil
city: Nantes Cedex 1
country: France
facility: Hospital Mere-Enfant
city: Paris
country: France
facility: Hospital Robert Debre
city: Berlin
country: Germany
facility: Campus Charite Mitte
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Mannheim
country: Germany
facility: Universitaetsklinikum Mannheim
city: Marburg
country: Germany
facility: Universitaetsklinikum Marburg
city: Muenchen
country: Germany
facility: Universitaetsklinikum Muenchen
city: Tuebingen
country: Germany
facility: Universitaeklinikum Tuebingen
city: Ulm
country: Germany
facility: Univeritaetsklinik Ulm
city: Ancona
country: Italy
facility: Az. Osp. G. Salesi
city: Bergamo
country: Italy
facility: Ospedali Riuniti
city: Bologna
country: Italy
facility: Policlinico S. Orsola
city: Firenze
country: Italy
facility: Azienda Ospedaliera Careggi
city: Padova
country: Italy
facility: University Padova
city: Roma
country: Italy
facility: Policlinico Gemelli
city: Groningen
country: Netherlands
facility: Beatrix Children's Hospital, University Medical Center Groningen
city: Rotterdam
country: Netherlands
facility: Sophia Kinderziekenhuis
city: Barakaldo
country: Spain
facility: Hospital de Cruces
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Mar
city: Madrid
country: Spain
facility: Hosspital Univeritario La Paz
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital Universitario Canarias
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Stockholm
country: Sweden
facility: Astrid Lindgrens barnsjukjus, Karolinska Unviersritets sjukhuset-Solna
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Gillingham
country: United Kingdom
facility: Meedway Mariton Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Kings College
Study officials:
affiliation: Mallinckrodt
name: Clinical Team Leader
role: STUDY_DIRECTOR
References:
citation: Laube M, Amann E, Uhlig U, Yang Y, Fuchs HW, Zemlin M, Mercier JC, Maier RF, Hummler HD, Uhlig S, Thome UH. Inflammatory Mediators in Tracheal Aspirates of Preterm Infants Participating in a Randomized Trial of Inhaled Nitric Oxide. PLoS One. 2017 Jan 3;12(1):e0169352. doi: 10.1371/journal.pone.0169352. eCollection 2017.
citation: Durrmeyer X, Hummler H, Sanchez-Luna M, Carnielli VP, Field D, Greenough A, Van Overmeire B, Jonsson B, Hallman M, Mercier JC, Marlow N, Johnson S, Baldassarre J; European Union Nitric Oxide Study Group. Two-year outcomes of a randomized controlled trial of inhaled nitric oxide in premature infants. Pediatrics. 2013 Sep;132(3):e695-703. doi: 10.1542/peds.2013-0007. Epub 2013 Aug 12.
citation: Mercier JC, Hummler H, Durrmeyer X, Sanchez-Luna M, Carnielli V, Field D, Greenough A, Van Overmeire B, Jonsson B, Hallman M, Baldassarre J; EUNO Study Group. Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO): a randomised controlled trial. Lancet. 2010 Jul 31;376(9738):346-54. doi: 10.1016/S0140-6736(10)60664-2. Epub 2010 Jul 23.