PrematurityPhase 2/3NOVA2NCT00515281
Inhaled Nitric Oxide and Neuroprotection in Premature Infants
A Phase 2/3 study testing inhaled nitric oxide and oxygen in people with Prematurity and Bronchopulmonary Dysplasia, run by University of Chicago at 1 site in United States.
Trial summary
The purpose of this study is to determine whether inhaled nitric oxide improves the neurological outcome for premature infants. Read more about this study
- Who is it for?
- Ages 2 to 72 hours
- Conditions the study is for
- Prematurity, Bronchopulmonary Dysplasia, Intraventricular Hemorrhage
- What is being tested?
- inhaled nitric oxide and oxygen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 273 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to 28 Nov 2023
- Phase
- Phase 2/3
- 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 2 to 72 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Prematurity (birthweight ≤ 1500g, < 31 weeks gestation)
- Requiring respiratory support
- Admitted to the NICU at the University of Chicago
Who cannot join
- Severe congenital anomalies
- Genetic syndromes
- Extremely sick preterm infants requiring very high ventilatory pressures (OI ≥ 20)
- Premature infants judged by the physician as nonviable
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine whether inhaled nitric oxide improves the neurological outcome for premature infants.
Read the detailed description
With the advances in modern neonatal intensive care medicine in the last 20 years, survival of extremely preterm infants weighing less than 1500g (< 3 lbs, 5 oz) has risen markedly. However, with this increased survival has come a marked increase in the number of infants with serious neurodevelopmental disabilities: Premature infants with birth weights less than 1500g who survive to go home are at significant risk for serious neurodevelopmental problems: cognitive and motor delays, blindness, deafness, and cerebral palsy. In a recent randomized, placebo-controlled clinical trial, we assessed whether giving mechanically ventilated preterm infants inhaled nitric oxide gas (iNO) for 1 week after birth decreased the incidence of death and chronic lung disease. An unanticipated outcome of that study (Schreiber et. al. 2003) and a subsequent study of those infants at 2 years of age (Mestan et. al. 2005) was that premature infants treated with inhaled nitric oxide (iNO) have improved neurodevelopmental outcomes and physical growth at 2 years corrected age, compared with placebo-treated infants (Mestan et. al. 2005). INO therapy, therefore, appears to be a new treatment to protect the premature brain during development outside the womb. The overall goal of this application is understand the efficacy of iNO treatment in improving neurodevelopmental outcomes in at-risk premature infants.
- Conditions
- Prematurity, Bronchopulmonary Dysplasia, Intraventricular Hemorrhage, Periventricular Leukomalacia
- Being tested
- inhaled nitric oxide, oxygen
- Keywords
- prematurity, nitric oxide, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, neurodevelopment
- Medical subject headings
- Premature Birth, Bronchopulmonary Dysplasia, Leukomalacia, Periventricular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
inhaled nitric oxideDrug
Also called INO
The amount of gas will be carefully controlled and adjusted to the level that best improves the function of subject's lungs. The subject will remain on inhaled nitric oxide until he/she reaches 33 weeks of gestation if assigned to the treatment arm, or until the 8th day of the study if he/she is assigned to the control arm.
oxygenDrug
Also called O2
The amount of gas will be carefully controlled and adjusted to the level that best improves the function of the subject's lungs. Subjects in the control arm of the study will receive oxygen beginning on the 8th day of the study until he/she reaches 33 weeks of gestation.
| Study group | Role | What they receive |
|---|---|---|
| INO Control (Short iNO) | Placebo comparator | INO will be given to infants in the control group for the first 7 days of the study gas, then O2 or room air, as clinically appropriate, on the 8th day, until 33 weeks corrected age Receives: Drug: inhaled nitric oxide |
| INO Treatment (Long iNO) | Experimental | The treatment group will receive iNO, combined with O2 or room air, until 33 weeks corrected age. Receives: Drug: inhaled nitric oxide; Drug: oxygen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurodevelopment
Measured: Two years
Bronchopulmonary Dysplasia (BPD) or Death
Need for respiratory support at 36 weeks post-menstrual age, either as positive pressure or supplemental oxygen to maintain oxygen saturations >90%, or death before discharge
Measured: 36 weeks of age corrected (BPD) or before discharge (death)
Secondary outcomes (6)
Death
Death before discharge
Measured: through discharge (up to 400 days)
Bronchopulmonary Dysplasia
Need for respiratory support at 36 weeks post-menstrual age (PMA), either as positive pressure or supplemental oxygen to maintain oxygen saturations >90%
Measured: 36 weeks of age corrected
Supplemental Oxygen Use
Measured: 40 weeks PMA
BPD or Death in Infants Weighing < 750g
Need for respiratory support at 36 weeks post-menstrual age, either as positive pressure or supplemental oxygen to maintain oxygen saturations >90%, or death before discharge among infants < 750g
Measured: 36 weeks of age corrected (BPD) or before discharge (death)
BPD or Death in Infants Weighing 750-999g
Need for respiratory support at 36 weeks post-menstrual age, either as positive pressure or supplemental oxygen to maintain oxygen saturations >90%, or death before discharge among infants 750-999g
Measured: 36 weeks of age corrected (BPD) or before discharge (death)
BPD or Death in Black Infants
Need for respiratory support at 36 weeks post-menstrual age, either as positive pressure or supplemental oxygen to maintain oxygen saturations >90%, or death before discharge among Black infants
Measured: 36 weeks of age corrected (BPD) or before discharge (death)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2007 (estimated)
- Study startMay 2008
- Primary completion7 Jun 2023
- Study completion28 Nov 2023
Why it stopped: The pace of patient enrolledment forced recruitment to stop after 273 patients.
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 (2)Papers the sponsor has linked to this study.
- Other trials for PrematurityStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe 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 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 273 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael D. Schreiber, M.D., Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00515281
- Sponsor's protocol ID
- 15405A
- Acronym
- NOVA2
- Status last verified
- Jul 2024
- First submitted
- 9 Aug 2007
- Last updated
- 17 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Schreiber MD, Gin-Mestan K, Marks JD, Huo D, Lee G, Srisuparp P. Inhaled nitric oxide in premature infants with the respiratory distress syndrome. N Engl J Med. 2003 Nov 27;349(22):2099-107. doi: 10.1056/NEJMoa031154.
PubMed 14645637Mestan KK, Marks JD, Hecox K, Huo D, Schreiber MD. Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide. N Engl J Med. 2005 Jul 7;353(1):23-32. doi: 10.1056/NEJMoa043514.
PubMed 16000353
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled Nitric Oxide and Neuroprotection in Premature Infants
- ClinicalTrials.gov ID
- NCT00515281
- Acronym / sponsor ID
- NOVA2 / 15405A
- Conditions
- Prematurity, Bronchopulmonary Dysplasia, Intraventricular Hemorrhage, Periventricular Leukomalacia
- Keywords
- prematurity, nitric oxide, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, neurodevelopment
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The pace of patient enrolledment forced recruitment to stop after 273 patients.
- Enrolment
- 273 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- May 2008 (actual)
- Primary completion
- 7 Jun 2023 (actual)
- Study completion
- 28 Nov 2023 (actual)
- First posted
- 13 Aug 2007 (estimated)
- Results
- Posted 17 Oct 2024
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 determine whether inhaled nitric oxide improves the neurological outcome for premature infants.
Detailed description
With the advances in modern neonatal intensive care medicine in the last 20 years, survival of extremely preterm infants weighing less than 1500g (< 3 lbs, 5 oz) has risen markedly. However, with this increased survival has come a marked increase in the number of infants with serious neurodevelopmental disabilities: Premature infants with birth weights less than 1500g who survive to go home are at significant risk for serious neurodevelopmental problems: cognitive and motor delays, blindness, deafness, and cerebral palsy. In a recent randomized, placebo-controlled clinical trial, we assessed whether giving mechanically ventilated preterm infants inhaled nitric oxide gas (iNO) for 1 week after birth decreased the incidence of death and chronic lung disease. An unanticipated outcome of that study (Schreiber et. al. 2003) and a subsequent study of those infants at 2 years of age (Mestan et. al. 2005) was that premature infants treated with inhaled nitric oxide (iNO) have improved neurodevelopmental outcomes and physical growth at 2 years corrected age, compared with placebo-treated infants (Mestan et. al. 2005). INO therapy, therefore, appears to be a new treatment to protect the premature brain during development outside the womb. The overall goal of this application is understand the efficacy of iNO treatment in improving neurodevelopmental outcomes in at-risk premature infants.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| INO Control (Short iNO) | Placebo comparator | Drug: inhaled nitric oxideINO will be given to infants in the control group for the first 7 days of the study gas, then O2 or room air, as clinically appropriate, on the 8th day, until 33 weeks corrected age |
| INO Treatment (Long iNO) | Experimental | Drug: inhaled nitric oxide, Drug: oxygenThe treatment group will receive iNO, combined with O2 or room air, until 33 weeks corrected age. |
Who may qualify
- Ages
- 2 to 72 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Prematurity (birthweight ≤ 1500g, < 31 weeks gestation)
- Requiring respiratory support
- Admitted to the NICU at the University of Chicago
Key exclusion criteria (4 listed)
- Severe congenital anomalies
- Genetic syndromes
- Extremely sick preterm infants requiring very high ventilatory pressures (OI ≥ 20)
- Premature infants judged by the physician as nonviable
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 |
|---|---|---|
| inhaled nitric oxideAlso: INOThe amount of gas will be carefully controlled and adjusted to the level that best improves the function of subject's lungs. The subject will remain on inhaled nitric oxide until he/she reaches 33 weeks of gestation if assigned to the treatment arm, or until the 8th day of the study if he/she is assigned to the control arm. | Drug | INO Control (Short iNO), INO Treatment (Long iNO) |
| oxygenAlso: O2The amount of gas will be carefully controlled and adjusted to the level that best improves the function of the subject's lungs. Subjects in the control arm of the study will receive oxygen beginning on the 8th day of the study until he/she reaches 33 weeks of gestation. | Drug | INO Treatment (Long iNO) |
Primary outcome
Neurodevelopment
Time frame: Two years
Bronchopulmonary Dysplasia (BPD) or Death
Time frame: 36 weeks of age corrected (BPD) or before discharge (death)
Need for respiratory support at 36 weeks post-menstrual age, either as positive pressure or supplemental oxygen to maintain oxygen saturations >90%, or death before discharge
6 secondary outcomes
Death
Time frame: through discharge (up to 400 days)
Bronchopulmonary Dysplasia
Time frame: 36 weeks of age corrected
Supplemental Oxygen Use
Time frame: 40 weeks PMA
BPD or Death in Infants Weighing < 750g
Time frame: 36 weeks of age corrected (BPD) or before discharge (death)
BPD or Death in Infants Weighing 750-999g
Time frame: 36 weeks of age corrected (BPD) or before discharge (death)
BPD or Death in Black Infants
Time frame: 36 weeks of age corrected (BPD) or before discharge (death)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 14645637Schreiber MD, Gin-Mestan K, Marks JD, Huo D, Lee G, Srisuparp P. Inhaled nitric oxide in premature infants with the respiratory distress syndrome. N Engl J Med. 2003 Nov 27;349(22):2099-107. doi: 10.1056/NEJMoa031154.
- Background: PubMed 16000353Mestan KK, Marks JD, Hecox K, Huo D, Schreiber MD. Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide. N Engl J Med. 2005 Jul 7;353(1):23-32. doi: 10.1056/NEJMoa043514.
- Individual participant dataSharing planned: Undecided
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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.
Michael D. Schreiber, M.D. principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing inhaled nitric oxide and oxygen in people with Prematurity and Bronchopulmonary Dysplasia, run by University of Chicago at 1 site in United States.
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 3 inclusion and 4 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: stopped early, as of the sponsor's last update on 17 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 17 Oct 2024). 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?
Neurodevelopment (time frame: Two years). The study lists 2 primary outcomes in all. 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 NCT00515281, which also lists 2 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 17 Oct 2024.