NCT00551642

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
800

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started May 2005

Longer than P75 for phase_3

Geographic Reach
9 countries

35 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 29, 2005

Completed
2.4 years until next milestone

First Submitted

Initial submission to the registry

October 30, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 31, 2007

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 16, 2008

Completed
2.6 years until next milestone

Results Posted

Study results publicly available

October 18, 2010

Completed
4.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 17, 2015

Completed
Last Updated

February 5, 2021

Status Verified

February 1, 2021

Enrollment Period

2.8 years

First QC Date

October 30, 2007

Results QC Date

September 3, 2010

Last Update Submit

February 4, 2021

Conditions

Lung Disease

Keywords

Preemie, Inhaled Nitric Oxide

Outcome Measures

Primary Outcomes (1)

  • Survival Without Bronchopulmonary Dysplasia (BPD) in Preterm Infants With Respiratory Distress

    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

    21 days

Other Outcomes (2)

  • Mortality at 7-year Follow-up

    at 7-year Follow-up

  • Strengths and Difficulties Questionnaire Results for Participants at 7-year Follow-up

    At 7-year Follow-up

Study Arms (2)

Inhaled Nitric Oxide (INO)

ACTIVE COMPARATOR

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

Drug: Nitric oxide

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Nitric oxideDRUG

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

Also known as: INO max®
Inhaled Nitric Oxide (INO)
PlaceboDRUG

Placebo gas for inhalation

Placebo

Eligibility Criteria

AgeUp to 26 Hours
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (35)

UCL St. LUC

Brussels, Belgium

Location

Clinique Notre Dame

Charleroi, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, Belgium

Location

Clinique St. Vincent CHC

Rocourt, Belgium

Location

Oulun yliopsistollinen sairaala

Oulu, FI-90220, Finland

Location

Centre Hospitalier Intercommunal de Creteil

Créteil, 94000, France

Location

Hospital Mere-Enfant

Nantes, 44093, France

Location

Hospital Robert Debre

Paris, 75019, France

Location

Campus Charite Mitte

Berlin, 10117, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69115, Germany

Location

Universitaetsklinikum Mannheim

Mannheim, 68167, Germany

Location

Universitaetsklinikum Marburg

Marburg, 35033, Germany

Location

Universitaetsklinikum Muenchen

München, 81377, Germany

Location

Universitaeklinikum Tuebingen

Tübingen, 72076, Germany

Location

Univeritaetsklinik Ulm

Ulm, 89075, Germany

Location

Az. Osp. G. Salesi

Ancona, 60123, Italy

Location

Ospedali Riuniti

Bergamo, 24128, Italy

Location

Policlinico S. Orsola

Bologna, 40138, Italy

Location

Azienda Ospedaliera Careggi

Florence, 50134, Italy

Location

University Padova

Padua, 35128, Italy

Location

Policlinico Gemelli

Roma, 00168, Italy

Location

Beatrix Children's Hospital, University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Sophia Kinderziekenhuis

Rotterdam, 3000 CB, Netherlands

Location

Hospital de Cruces

Barakaldo, 48903, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Gregorio Mar

Madrid, 28007, Spain

Location

Hosspital Univeritario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Canarias

Santa Cruz de Tenerife, 38320, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitario La Fe

Valencia, 46009, Spain

Location

Astrid Lindgrens barnsjukjus, Karolinska Unviersritets sjukhuset-Solna

Stockholm, SE-171 76, Sweden

Location

Akademiska Sjukhuset

Uppsala, SE-751 85, Sweden

Location

Meedway Mariton Hospital

Gillingham, ME7 5NY, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Kings College

London, SE5 9RS, United Kingdom

Location

Related Publications (3)

  • 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.

    PMID: 28046032DERIVED

  • 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.

    PMID: 23940237DERIVED

  • 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.

    PMID: 20655106DERIVED

MeSH Terms

Conditions

Lung Diseases

Interventions

Nitric Oxide

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Reactive Nitrogen SpeciesFree RadicalsInorganic ChemicalsNitrogen OxidesNitrogen CompoundsOxidesOxygen CompoundsOrganic Chemicals

Results Point of Contact

Title
Medical Information Call Center
Organization
Mallinckrodt
medinfo@mnk.com
800-556-3314

Study Officials

  • Clinical Team Leader

    Mallinckrodt

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 30, 2007

First Posted

October 31, 2007

Study Start

May 29, 2005

Primary Completion

March 16, 2008

Study Completion

July 17, 2015

Last Updated

February 5, 2021

Results First Posted

October 18, 2010

Record last verified: 2021-02

Data Sharing

IPD Sharing
Will not share

Discussion of statistical endpoints and analysis are included in manuscripts. Summary aggregate (basic) results (including adverse events information) and the study protocol are made available on clinicaltrials.gov (NCT00551642) when required by regulation. Individual de-identified patient data will not be disclosed. Requests for additional information should be directed to the company at medinfo@mnk.com.

Locations

FR(3)NL(2)GB(3)BE(4)FI(1)DE(7)IT(6)ES(7)SE(2)