Lung DiseasePhase 3NCT00551642
Safety and Efficacy Study of Nitric Oxide for Inhalation on Chronic Lung Disease in Premature Babies
A Phase 3 study testing Nitric oxide in people with Lung Disease, run by Mallinckrodt at 35 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 26 hours
- Conditions the study is for
- Lung Disease
- What is being tested?
- Nitric oxide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 800 participants
- Where
- 35 sitesin 9 countries
- Study dates
- 29 May 2005to 17 Jul 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 26 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
35 sites in 9 countries.
35 sites in 9 countries
Germany7 sites
Campus Charite Mitte
Berlin, 10117
Universitaetsklinikum Heidelberg
Heidelberg, 69115
Universitaetsklinikum Mannheim
Mannheim, 68167
Universitaetsklinikum Marburg
Marburg, 35033
Universitaetsklinikum Muenchen
München, 81377
Universitaeklinikum Tuebingen
Tübingen, 72076
Univeritaetsklinik Ulm
Ulm, 89075
Spain7 sites
Hospital de Cruces
Barakaldo, 48903
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Hospital Universitario Gregorio Mar
Madrid, 28007
Hosspital Univeritario La Paz
Madrid, 28046
Hospital Universitario Canarias
Santa Cruz de Tenerife, 38320
Hospital Universitario Virgen del Rocio
Seville, 41013
Hospital Universitario La Fe
Valencia, 46009
Italy6 sites
Az. Osp. G. Salesi
Ancona, 60123
Ospedali Riuniti
Bergamo, 24128
Policlinico S. Orsola
Bologna, 40138
Azienda Ospedaliera Careggi
Florence, 50134
University Padova
Padova, 35128
Policlinico Gemelli
Roma, 00168
Belgium4 sites
UCL St. LUC
Brussels
Clinique Notre Dame
Charleroi
Universitair Ziekenhuis Antwerpen
Edegem
Clinique St. Vincent CHC
Rocourt
France3 sites
Centre Hospitalier Intercommunal de Creteil
Créteil, 94000
Hospital Mere-Enfant
Nantes, 44093
Hospital Robert Debre
Paris, 75019
United Kingdom3 sites
Meedway Mariton Hospital
Gillingham, ME7 5NY
Leicester Royal Infirmary
Leicester, LE1 5WW
Kings College
London, SE5 9RS
Netherlands2 sites
Beatrix Children's Hospital, University Medical Center Groningen
Groningen, 9713 GZ
Sophia Kinderziekenhuis
Rotterdam, 3000 CB
Sweden2 sites
Astrid Lindgrens barnsjukjus, Karolinska Unviersritets sjukhuset-Solna
Stockholm, SE-171 76
Akademiska Sjukhuset
Uppsala, SE-751 85
About this study
Official title: The Effects of Nitric Oxide for Inhalation on the Development of Chronic Lung Disease in Pre-term Infants
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.
Read the 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
- Being tested
- Nitric oxide, Placebo
- Keywords
- Preemie, Inhaled Nitric Oxide
- Medical subject headings
- Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric oxideDrug
Also called INO max®
Nitric Oxide vapour (gas) for inhalation (400 ppm)
PlaceboDrug
Placebo gas for inhalation
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2007 (estimated)
- Study start29 May 2005
- Primary completion16 Mar 2008
- Study completion17 Jul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Lung DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 800 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mallinckrodt
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Team Leader, Study director, Mallinckrodt
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00551642
- Sponsor's protocol ID
- INOT27
- Other IDs
- 2004-002312-29, 2004
- Status last verified
- Feb 2021
- First submitted
- 30 Oct 2007
- Last updated
- 5 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Publications
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.
PubMed 28046032Durrmeyer 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.
PubMed 23940237Mercier 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.
PubMed 20655106
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Nitric Oxide for Inhalation on the Development of Chronic Lung Disease in Pre-term Infants
- ClinicalTrials.gov ID
- NCT00551642
- Acronym / sponsor ID
- INOT27
- Conditions
- Lung Disease
- Keywords
- Preemie, Inhaled Nitric Oxide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 800 participants (actual)
- Lead sponsor
- MallinckrodtIndustry (pharma, biotech, devices)
- Study start
- 29 May 2005 (actual)
- Primary completion
- 16 Mar 2008 (actual)
- Study completion
- 17 Jul 2015 (actual)
- First posted
- 31 Oct 2007 (estimated)
- Results
- Posted 18 Oct 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inhaled Nitric Oxide (INO) | Active comparator | Drug: 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 |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo gas administered by nasal continuous positive airway pressure, nasal cannula or face mask, for a maximum of 21 days. |
Who may qualify
- Ages
- Up to 26 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (7 listed)
- 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%.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitric oxideAlso: INO max®Nitric Oxide vapour (gas) for inhalation (400 ppm) | Drug | Inhaled Nitric Oxide (INO) |
| PlaceboPlacebo gas for inhalation | Drug | Placebo |
Primary outcome
Survival Without Bronchopulmonary Dysplasia (BPD) in Preterm Infants With Respiratory Distress
Time frame: 21 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28046032Laube 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.
- Derived from this study: PubMed 23940237Durrmeyer 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.
- Derived from this study: PubMed 20655106Mercier 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.
- Individual participant dataSharing planned: No. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Team Leader study director
Mallinckrodt
35 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nitric oxide in people with Lung Disease, run by Mallinckrodt at 35 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in Germany, Spain, Italy, Belgium, France and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Oct 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival Without Bronchopulmonary Dysplasia (BPD) in Preterm Infants With Respiratory Distress (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00551642, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2021.