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

NCT ID: NCT00551642

Last Updated: 2021-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 800 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-29
• Study Completion Date: 2015-07-17

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).

Conditions

Lung Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Inhaled Nitric Oxide (INO)

INO administered by nasal continuous positive airway pressure, nasal cannula or face mask at 5 parts per million (ppm) for between 7 and 21 days

Group Type: ACTIVE_COMPARATOR

Nitric oxide

Intervention Type: DRUG

Nitric Oxide vapour (gas) for inhalation (400 ppm)

Placebo

Placebo gas administered by nasal continuous positive airway pressure, nasal cannula or face mask, for a maximum of 21 days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo gas for inhalation

Interventions

Nitric oxide

Nitric Oxide vapour (gas) for inhalation (400 ppm)

Intervention Type: DRUG

Placebo

Placebo gas for inhalation

Intervention Type: DRUG

Other Intervention Names

INO max®

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.

• Maximum Eligible Age: 26 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mallinckrodt

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Team Leader

Role: STUDY_DIRECTOR

Mallinckrodt

Locations

UCL St. LUC

Brussels, , Belgium

Clinique Notre Dame

Charleroi, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Clinique St. Vincent CHC

Rocourt, , Belgium

Oulun yliopsistollinen sairaala

Oulu, , Finland

Centre Hospitalier Intercommunal de Creteil

Créteil, , France

Hospital Mere-Enfant

Nantes, , France

Hospital Robert Debre

Paris, , France

Campus Charite Mitte

Berlin, , Germany

Universitaetsklinikum Heidelberg

Heidelberg, , Germany

Universitaetsklinikum Mannheim

Mannheim, , Germany

Universitaetsklinikum Marburg

Marburg, , Germany

Universitaetsklinikum Muenchen

München, , Germany

Universitaeklinikum Tuebingen

Tübingen, , Germany

Univeritaetsklinik Ulm

Ulm, , Germany

Az. Osp. G. Salesi

Ancona, , Italy

Ospedali Riuniti

Bergamo, , Italy

Policlinico S. Orsola

Bologna, , Italy

Azienda Ospedaliera Careggi

Florence, , Italy

University Padova

Padua, , Italy

Policlinico Gemelli

Roma, , Italy

Beatrix Children's Hospital, University Medical Center Groningen

Groningen, , Netherlands

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

Seville, , Spain

Hospital Universitario La Fe

Valencia, , Spain

Astrid Lindgrens barnsjukjus, Karolinska Unviersritets sjukhuset-Solna

Stockholm, , Sweden

Akademiska Sjukhuset

Uppsala, , Sweden

Meedway Mariton Hospital

Gillingham, , United Kingdom

Leicester Royal Infirmary

Leicester, , United Kingdom

Kings College

London, , United Kingdom

Countries

Belgium; Finland; France; Germany; Italy; Netherlands; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 28046032 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23940237 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 20655106 (View on PubMed)

Other Identifiers

2004-002312-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INOT27

Identifier Type: -

Identifier Source: org_study_id