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

Phase 3
Completed
Conditions
Lung Disease
Interventions
Drug: Placebo
Registration Number
NCT00551642
Lead Sponsor
Mallinckrodt
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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
800
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo gas administered by nasal continuous positive airway pressure, nasal cannula or face mask, for a maximum of 21 days.
Inhaled Nitric Oxide (INO)Nitric oxideINO administered by nasal continuous positive airway pressure, nasal cannula or face mask at 5 parts per million (ppm) for between 7 and 21 days
Primary Outcome Measures
NameTimeMethod
Survival Without Bronchopulmonary Dysplasia (BPD) in Preterm Infants With Respiratory Distress21 days

Survival without BPD is defined as the number of preterm infants of 36 weeks gestational age who survived the treatment period without the need for supplemental oxygen

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (35)

Clinique St. Vincent CHC

🇧🇪

Rocourt, Belgium

Beatrix Children's Hospital, University Medical Center Groningen

🇳🇱

Groningen, Netherlands

Policlinico S. Orsola

🇮🇹

Bologna, Italy

Clinique Notre Dame

🇧🇪

Charleroi, Belgium

Centre Hospitalier Intercommunal de Creteil

🇫🇷

Creteil, France

Universitair Ziekenhuis Antwerpen

🇧🇪

Edegem, Belgium

Hospital Robert Debre

🇫🇷

Paris, France

Oulun yliopsistollinen sairaala

🇫🇮

Oulu, Finland

Campus Charite Mitte

🇩🇪

Berlin, Germany

Hospital Mere-Enfant

🇫🇷

Nantes Cedex 1, France

Universitaetsklinikum Marburg

🇩🇪

Marburg, Germany

Universitaeklinikum Tuebingen

🇩🇪

Tuebingen, Germany

Universitaetsklinikum Muenchen

🇩🇪

Muenchen, Germany

Universitaetsklinikum Heidelberg

🇩🇪

Heidelberg, Germany

Universitaetsklinikum Mannheim

🇩🇪

Mannheim, Germany

Univeritaetsklinik Ulm

🇩🇪

Ulm, Germany

Az. Osp. G. Salesi

🇮🇹

Ancona, Italy

Ospedali Riuniti

🇮🇹

Bergamo, Italy

Azienda Ospedaliera Careggi

🇮🇹

Firenze, Italy

Policlinico Gemelli

🇮🇹

Roma, Italy

University Padova

🇮🇹

Padova, Italy

Sophia Kinderziekenhuis

🇳🇱

Rotterdam, Netherlands

Hospital de Cruces

🇪🇸

Barakaldo, Spain

Hospital Universitario Vall d'Hebron

🇪🇸

Barcelona, Spain

Hospital Universitario Gregorio Mar

🇪🇸

Madrid, Spain

Hosspital Univeritario La Paz

🇪🇸

Madrid, Spain

Hospital Universitario Canarias

🇪🇸

Santa Cruz de Tenerife, Spain

Hospital Universitario Virgen del Rocio

🇪🇸

Sevilla, Spain

Hospital Universitario La Fe

🇪🇸

Valencia, Spain

Astrid Lindgrens barnsjukjus, Karolinska Unviersritets sjukhuset-Solna

🇸🇪

Stockholm, Sweden

Leicester Royal Infirmary

🇬🇧

Leicester, United Kingdom

Akademiska Sjukhuset

🇸🇪

Uppsala, Sweden

Kings College

🇬🇧

London, United Kingdom

Meedway Mariton Hospital

🇬🇧

Gillingham, United Kingdom

UCL St. LUC

🇧🇪

Bruxelles, Belgium

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