Bronchopulmonary DysplasiaPhase 3NCT00000548
Inhaled NO in Prevention of Chronic Lung Disease
A Phase 3 study testing mechanical ventilation in people with Bronchopulmonary Dysplasia and Lung Diseases, run by University of California, San Francisco.
Trial summary
To test the hypothesis that low-dose inhaled nitric oxide administered to preterm infants who continue to require mechanical ventilation at 14 days of age will reduce the incidence of chronic lung disease. Read more about this study
- Who is it for?
- Ages Up to 1 year
- Conditions the study is for
- Bronchopulmonary Dysplasia, Lung Diseases
- What is being tested?
- mechanical ventilation
- Type of treatment
- Surgery or procedure
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Mar 2000to Feb 2006
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 1 year
- All sexes
- No healthy volunteers
- Child
Preterm infants who are 500-1250 grams at birth and who require mechanical ventilation at 10 to 21 days of age. Exclusions include congenital heart disease or pulmonary abnormalities, including a patent ductus arteriosus, ventilation solely for apnea, small-for-gestational age, or clinical bleeding.
About this study
To test the hypothesis that low-dose inhaled nitric oxide administered to preterm infants who continue to require mechanical ventilation at 14 days of age will reduce the incidence of chronic lung disease.
Read the detailed description
BACKGROUND:
Respiratory morbidity, particularly chronic lung disease (CLD), remains a major cause of long-term morbidity and mortality for preterm infants. Although surfactant replacement has decreased acute respiratory morbidity and mortality, it has not reduced the incidence of CLD. A number of other approaches, including antenatal thyrotropin releasing hormone in conjunction with corticosteroids, postnatal steroid administration, as well as administration of Vitamin E, diuretics, and bronchodilators, have not resulted in clinically important decreases in CLD. Infants with the most severe CLD go on to develop findings suggestive of pulmonary hypertension with cor pulmonale. There is preliminary evidence in the preterm infant with severe chronic lung disease that low-dose inhaled nitric oxide may significantly attenuate the disease and decrease mortality.
DESIGN NARRATIVE:
The multi-center, controlled and blinded trial investigates the hypothesis that low-dose inhaled nitric oxide administered to preterm infants between 500 and 1250 grams birth weight who continue to require mechanical ventilation at 10 days of age will increase survival without chronic lung disease (CLD) at 36 weeks post menstrual age. Secondary outcomes are duration of ventilation, oxygen requirement and duration of hospitalization. In addition, that there will be expected improvement in infant respiratory status (ventilatory support, airway resistance and compliance) associated with inhaled nitric oxide treatment. Indicators of inflammation and oxidant stress will be assessed by measurements of specific cytokines and protein modifications in tracheal aspirate and plasma samples, respectively. The safety of this therapy will be evaluated by assessing toxicity as measured by clinical bleeding, including intraventricular hemorrhage as well as the incidence of other morbidities of the preterm infant (necrotizing enterocolitis, retinopathy of prematurity and infection) and assessing neurodevelopmental outcome through two years of age. A total of 480 infants were randomized to either inhaled NO or placebo. In summary, this clinical trial will assess the efficacy and safety of inhaled nitric oxide for amelioration of a major disease of premature infants.
- Conditions
- Bronchopulmonary Dysplasia, Lung Diseases
- Being tested
- mechanical ventilation
- Medical subject headings
- Bronchopulmonary Dysplasia, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mechanical ventilationProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival without chronic lung disease (CLD)
Measured: 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 1999 (estimated)
- Study startMar 2000
- Study completionFeb 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Bronchopulmonary DysplasiaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Masking
- Double blind
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Investigators
- Roberta Ballard, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000548
- Sponsor's protocol ID
- 92
- Other IDs
- U01HL062514
- Status last verified
- Mar 2015
- First submitted
- 27 Oct 1999
- Last updated
- 5 Mar 2015
- Results posted
- No
Publications
Ballard PL, Merrill JD, Godinez RI, Godinez MH, Truog WE, Ballard RA. Surfactant protein profile of pulmonary surfactant in premature infants. Am J Respir Crit Care Med. 2003 Nov 1;168(9):1123-8. doi: 10.1164/rccm.200304-479OC. Epub 2003 Aug 6.
PubMed 12904326Merrill JD, Ballard RA, Cnaan A, Hibbs AM, Godinez RI, Godinez MH, Truog WE, Ballard PL. Dysfunction of pulmonary surfactant in chronically ventilated premature infants. Pediatr Res. 2004 Dec;56(6):918-26. doi: 10.1203/01.PDR.0000145565.45490.D9. Epub 2004 Oct 20.
PubMed 15496605Ghotbi E, Hathaway QA, Jannatdoust P, Hadidchi R, Bancks MP, Bluemke DA, Budoff M, Post W, Hoffman EA, Smith BM, Lima JAC, Barr RG, Demehri S. CT Emphysema and Deep Learning-derived Vertebral Bone Loss in Individuals without COPD: Findings from MESA. Radiology. 2026 Apr;319(1):e252251. doi: 10.1148/radiol.252251.
PubMed 42012343Walsh MC, Hibbs AM, Martin CR, Cnaan A, Keller RL, Vittinghoff E, Martin RJ, Truog WE, Ballard PL, Zadell A, Wadlinger SR, Coburn CE, Ballard RA; NO CLD Study Group. Two-year neurodevelopmental outcomes of ventilated preterm infants treated with inhaled nitric oxide. J Pediatr. 2010 Apr;156(4):556-61.e1. doi: 10.1016/j.jpeds.2009.10.011. Epub 2010 Feb 6.
PubMed 20138299Zupancic JA, Hibbs AM, Palermo L, Truog WE, Cnaan A, Black DM, Ballard PL, Wadlinger SR, Ballard RA; NO CLD Trial Group. Economic evaluation of inhaled nitric oxide in preterm infants undergoing mechanical ventilation. Pediatrics. 2009 Nov;124(5):1325-32. doi: 10.1542/peds.2008-3214. Epub 2009 Oct 19.
PubMed 19841125Ballard RA, Truog WE, Cnaan A, Martin RJ, Ballard PL, Merrill JD, Walsh MC, Durand DJ, Mayock DE, Eichenwald EC, Null DR, Hudak ML, Puri AR, Golombek SG, Courtney SE, Stewart DL, Welty SE, Phibbs RH, Hibbs AM, Luan X, Wadlinger SR, Asselin JM, Coburn CE; NO CLD Study Group. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med. 2006 Jul 27;355(4):343-53. doi: 10.1056/NEJMoa061088.
PubMed 16870913
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled NO in Prevention of Chronic Lung Disease
- ClinicalTrials.gov ID
- NCT00000548
- Acronym / sponsor ID
- 92
- Conditions
- Bronchopulmonary Dysplasia, Lung Diseases
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Mar 2000
- Study completion
- Feb 2006 (actual)
- First posted
- 28 Oct 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To test the hypothesis that low-dose inhaled nitric oxide administered to preterm infants who continue to require mechanical ventilation at 14 days of age will reduce the incidence of chronic lung disease.
Detailed description
BACKGROUND:
Respiratory morbidity, particularly chronic lung disease (CLD), remains a major cause of long-term morbidity and mortality for preterm infants. Although surfactant replacement has decreased acute respiratory morbidity and mortality, it has not reduced the incidence of CLD. A number of other approaches, including antenatal thyrotropin releasing hormone in conjunction with corticosteroids, postnatal steroid administration, as well as administration of Vitamin E, diuretics, and bronchodilators, have not resulted in clinically important decreases in CLD. Infants with the most severe CLD go on to develop findings suggestive of pulmonary hypertension with cor pulmonale. There is preliminary evidence in the preterm infant with severe chronic lung disease that low-dose inhaled nitric oxide may significantly attenuate the disease and decrease mortality.
DESIGN NARRATIVE:
The multi-center, controlled and blinded trial investigates the hypothesis that low-dose inhaled nitric oxide administered to preterm infants between 500 and 1250 grams birth weight who continue to require mechanical ventilation at 10 days of age will increase survival without chronic lung disease (CLD) at 36 weeks post menstrual age. Secondary outcomes are duration of ventilation, oxygen requirement and duration of hospitalization. In addition, that there will be expected improvement in infant respiratory status (ventilatory support, airway resistance and compliance) associated with inhaled nitric oxide treatment. Indicators of inflammation and oxidant stress will be assessed by measurements of specific cytokines and protein modifications in tracheal aspirate and plasma samples, respectively. The safety of this therapy will be evaluated by assessing toxicity as measured by clinical bleeding, including intraventricular hemorrhage as well as the incidence of other morbidities of the preterm infant (necrotizing enterocolitis, retinopathy of prematurity and infection) and assessing neurodevelopmental outcome through two years of age. A total of 480 infants were randomized to either inhaled NO or placebo. In summary, this clinical trial will assess the efficacy and safety of inhaled nitric oxide for amelioration of a major disease of premature infants.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Masking
- Double blind
Who may qualify
- Ages
- Up to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
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 |
|---|---|---|
| mechanical ventilation | Procedure or surgery | – |
Primary outcome
Survival without chronic lung disease (CLD)
Time frame: 36 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2015.
- Background: PubMed 12904326Ballard PL, Merrill JD, Godinez RI, Godinez MH, Truog WE, Ballard RA. Surfactant protein profile of pulmonary surfactant in premature infants. Am J Respir Crit Care Med. 2003 Nov 1;168(9):1123-8. doi: 10.1164/rccm.200304-479OC. Epub 2003 Aug 6.
- Background: PubMed 15496605Merrill JD, Ballard RA, Cnaan A, Hibbs AM, Godinez RI, Godinez MH, Truog WE, Ballard PL. Dysfunction of pulmonary surfactant in chronically ventilated premature infants. Pediatr Res. 2004 Dec;56(6):918-26. doi: 10.1203/01.PDR.0000145565.45490.D9. Epub 2004 Oct 20.
- Derived from this study: PubMed 42012343Ghotbi E, Hathaway QA, Jannatdoust P, Hadidchi R, Bancks MP, Bluemke DA, Budoff M, Post W, Hoffman EA, Smith BM, Lima JAC, Barr RG, Demehri S. CT Emphysema and Deep Learning-derived Vertebral Bone Loss in Individuals without COPD: Findings from MESA. Radiology. 2026 Apr;319(1):e252251. doi: 10.1148/radiol.252251.
- Derived from this study: PubMed 20138299Walsh MC, Hibbs AM, Martin CR, Cnaan A, Keller RL, Vittinghoff E, Martin RJ, Truog WE, Ballard PL, Zadell A, Wadlinger SR, Coburn CE, Ballard RA; NO CLD Study Group. Two-year neurodevelopmental outcomes of ventilated preterm infants treated with inhaled nitric oxide. J Pediatr. 2010 Apr;156(4):556-61.e1. doi: 10.1016/j.jpeds.2009.10.011. Epub 2010 Feb 6.
- Derived from this study: PubMed 19841125Zupancic JA, Hibbs AM, Palermo L, Truog WE, Cnaan A, Black DM, Ballard PL, Wadlinger SR, Ballard RA; NO CLD Trial Group. Economic evaluation of inhaled nitric oxide in preterm infants undergoing mechanical ventilation. Pediatrics. 2009 Nov;124(5):1325-32. doi: 10.1542/peds.2008-3214. Epub 2009 Oct 19.
- Derived from this study: PubMed 16870913Ballard RA, Truog WE, Cnaan A, Martin RJ, Ballard PL, Merrill JD, Walsh MC, Durand DJ, Mayock DE, Eichenwald EC, Null DR, Hudak ML, Puri AR, Golombek SG, Courtney SE, Stewart DL, Welty SE, Phibbs RH, Hibbs AM, Luan X, Wadlinger SR, Asselin JM, Coburn CE; NO CLD Study Group. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med. 2006 Jul 27;355(4):343-53. doi: 10.1056/NEJMoa061088.
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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.
Roberta Ballard
Children's Hospital of Philadelphia
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing mechanical ventilation in people with Bronchopulmonary Dysplasia and Lung Diseases, run by University of California, San Francisco.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 chronic lung disease (CLD) (time frame: 36 weeks). 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 NCT00000548, which also lists 6 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 Mar 2015.