Persistent Fetal Circulation SyndromePhase 4NCT01891500
Early iNO for Oxidative Stress, Vascular Tone and Inflammation in Babies With Hypoxic Respiratory Failure
A Phase 4 study testing Inhaled nitric oxide, Nitrogen Gas and Crossover iNO in people with Persistent Fetal Circulation Syndrome and Hypertension, Pulmonary, of Newborn, Persistent, run by University of Florida at 1 site in United States.
Trial summary
The investigators in this study are concerned about the harmful effects of oxygen exposure in newborn infants, particularly at high concentrations. Inhaled nitric oxide (iNO) is an FDA approved drug for the treatment of hypoxic respiratory failure (HRF) in term and late-preterm babies greater than 34 weeks gestation. Read more about this study
- Who is it for?
- Ages 30 minutes to 48 hours
- Conditions the study is for
- Persistent Fetal Circulation Syndrome, Hypertension, Pulmonary, of Newborn, Persistent, Persistent Pulmonary Hypertension of Newborn
- What is being tested?
- Inhaled nitric oxide, Nitrogen Gas and Crossover iNO
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- May 2016to 19 Sep 2019
- Phase
- Phase 4
- 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 30 minutes to 48 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Gestational age ≥ 35 weeks gestation
- Age of life ≤ 48 hours
- Diagnosis of hypoxic respiratory failure (HRF) as defined by a post-ductal SaO2 ≤90% in ≥50% oxygen with a PEEP of ≥ 6cm or an oxygenation index (OI) ≥ 10 but ≤ 15 when mean airway pressure and PaO2 are known.
- Mothers (ages 18 - 65) of eligible subjects for additional data collection
Who cannot join
- Gestational age < 35 weeks gestation.
- Post-natal age > 48 hours.
- Previous treatment with 100% oxygen for longer than 4 hours.
- Confirmed congenital diaphragmatic hernia.
- Suspected or confirmed congenital airway or pulmonary anomaly.
- Suspected or confirmed chromosomal anomaly or genetic aberration, with the exception of patients with trisomy 21 who do not have complex congenital heart disease.
- Infants with pneumothorax as the primary cause of their HRF.
- Infants with confirmed complex congenital heart disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
Shands Hospital at the University of Florida
Gainesville, Florida, 32610
About this study
Official title: Effect of Early iNO on Oxidative Stress, Vascular Tone and Inflammation in Term and Late-Preterm Infants With Hypoxic Respiratory Failure
The investigators in this study are concerned about the harmful effects of oxygen exposure in newborn infants, particularly at high concentrations. Inhaled nitric oxide (iNO) is an FDA approved drug for the treatment of hypoxic respiratory failure (HRF) in term and late-preterm babies greater than 34 weeks gestation. Hypoxic respiratory failure occurs when a patient's lungs cannot get enough oxygen into their bloodstream. This condition is traditionally treated with high concentrations of oxygen and most often requires the patient be placed on a ventilator (breathing machine). The administration of inhaled nitric oxygen directly into the lungs often improves blood oxygen levels and allows caretakers to reduce the amount of oxygen given to the baby. The purpose of this research study is to evaluate if giving the inhaled nitric oxide earlier in the course of disease improves the effectiveness of the drug, reduces the amount of cellular injury from oxygen exposure, and decreases the total amount of time a patient requires supplemental oxygen. This study uses an FDA approved drug in a new manner.
- Conditions
- Persistent Fetal Circulation Syndrome, Hypertension, Pulmonary, of Newborn, Persistent, Persistent Pulmonary Hypertension of Newborn
- Being tested
- Inhaled nitric oxide, Nitrogen Gas, Crossover iNO
- Keywords
- Persistent Fetal Circulation Syndrome, Infant, Newborn, Nitric Oxide, Oxidative Stress, Endothelin 1, Vascular Endothelial Growth Factor
- Medical subject headings
- Persistent Fetal Circulation Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inhaled nitric oxideDrug
Also called INOmax
Drug is initiated at 20ppm. Patients randomized to receive iNO at OI 10-15.
Nitrogen GasDrug
Also called bioinert
Placebo gas (bioinert), Patients randomized to bioinert inhaled gas at OI 10-15.
Crossover iNODrug
Also called bioinert, INOmax
Patients who deteriorate (OI >20 on two consecutive blood gases) will be unblinded. If they are receiving placebo gas, they will be started on iNO and make up the crossover cohort.
| Study group | Role | What they receive |
|---|---|---|
| Early inhaled nitric oxide | Experimental | Patients randomized to receive iNO at OI 10-15. Receives: Drug: Inhaled nitric oxide |
| Bioinert inhaled gas (nitrogen gas) | Placebo comparator | Patients randomized to bioinert inhaled gas at OI 10-15. Receives: Drug: Nitrogen Gas |
| Crossover iNO | Active comparator | Patients who deteriorate (OI >20 on two consecutive blood gases) will be unblinded. If they are receiving placebo gas, they will be started on iNO and make up the crossover cohort. Receives: Drug: Crossover iNO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biomarkers of oxidative injury.
Early administration of iNO to infants with HRF will result in reduced hyperoxia-mediated oxidative injury as measured by known biomarkers of oxygen free radical injury, including malondialdehyde and 8-hydroxy-2'-deoxyguanosine.
Measured: Urine samples will be collected upon enrollment and then at specific time points within the first 48 hours of study intervention to compare the change in biomarker concentrations from baseline up to hour 48.
Secondary outcomes (5)
Responsiveness to study treatment.
Earlier administration of iNO to infants with HRF/PPHN (persistent pulmonary hypertension of the newborn) will lessen reactive oxygen species formation resulting in improved responsiveness to the drug as measured by the initial changes in arterial oxygen concentration after administration of the drug.
Measured: Arterial oxygen concentration will be measured upon enrollment and at specific time points in the first 36 hours of study intervention to compare the change in arterial oxygen concentration from baseline up to hour 36.
Expression of endothelin-1.
Earlier treatment with iNO may potentiate pulmonary vasodilation by modulating endothelin-1 expression.
Measured: Concentration of endothelin-1 will be measured upon enrollment and at specific time points in the first 36 hours of study intervention to compare the change in concentration from baseline up to hour 36.
Markers of inflammation.
Early iNO may up-regulate production of endogenous anti-inflammatory eicosanoids such as PGE2 (prostaglandin E2). Additionally, avoidance of hyperoxia in these patients may mitigate pro-inflammatory cytokines known to potentiate lung injury.
Measured: Concentrations of pro and anti-inflammatory markers will be measured upon enrollment and at specific time points in the first 36 hours of study intervention to compare the change in concentrations from baseline up to hour 36.
Duration of oxygen treatment.
Early administration of iNO to infants with HRF will result in at least a 15% reduction in total days of oxygen therapy.
Measured: Participants will be followed for the duration of their hospital stay, with an expected average stay of 4 weeks.
Expression of VEGF (vascular endothelial growth factor).
Earlier treatment with iNO may potentiate pulmonary vasodilation by preventing hyperoxic down regulation of VEGF.
Measured: Concentration of VEGF will be measured upon enrollment and at specific time points in the first 36 hours of study intervention to compare the change in concentration from baseline up to hour 36.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2013 (estimated)
- Study startMay 2016
- Primary completion18 Sep 2019
- Study completion19 Sep 2019
Why it stopped: Difficult to identify subjects who meet enrollment criteria.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Persistent Fetal Circulation SyndromeStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Mallinckrodt
- Responsible party
- Sponsor
- Investigators
- Catalina Bazacliu, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01891500
- Sponsor's protocol ID
- IRB201400791
- Other IDs
- 00089105, OCR17867
- Status last verified
- Jan 2020
- First submitted
- 19 Jun 2013
- Last updated
- 7 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Early iNO on Oxidative Stress, Vascular Tone and Inflammation in Term and Late-Preterm Infants With Hypoxic Respiratory Failure
- ClinicalTrials.gov ID
- NCT01891500
- Acronym / sponsor ID
- IRB201400791
- Conditions
- Persistent Fetal Circulation Syndrome, Hypertension, Pulmonary, of Newborn, Persistent, Persistent Pulmonary Hypertension of Newborn
- Keywords
- Persistent Fetal Circulation Syndrome, Infant, Newborn, Nitric Oxide, Oxidative Stress, Endothelin 1, Vascular Endothelial Growth Factor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Difficult to identify subjects who meet enrollment criteria.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Mallinckrodt
- Study start
- May 2016 (actual)
- Primary completion
- 18 Sep 2019 (actual)
- Study completion
- 19 Sep 2019 (actual)
- First posted
- 3 Jul 2013 (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.
The investigators in this study are concerned about the harmful effects of oxygen exposure in newborn infants, particularly at high concentrations. Inhaled nitric oxide (iNO) is an FDA approved drug for the treatment of hypoxic respiratory failure (HRF) in term and late-preterm babies greater than 34 weeks gestation. Hypoxic respiratory failure occurs when a patient's lungs cannot get enough oxygen into their bloodstream. This condition is traditionally treated with high concentrations of oxygen and most often requires the patient be placed on a ventilator (breathing machine). The administration of inhaled nitric oxygen directly into the lungs often improves blood oxygen levels and allows caretakers to reduce the amount of oxygen given to the baby. The purpose of this research study is to evaluate if giving the inhaled nitric oxide earlier in the course of disease improves the effectiveness of the drug, reduces the amount of cellular injury from oxygen exposure, and decreases the total amount of time a patient requires supplemental oxygen. This study uses an FDA approved drug in a new manner.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Early inhaled nitric oxide | Experimental | Drug: Inhaled nitric oxidePatients randomized to receive iNO at OI 10-15. |
| Bioinert inhaled gas (nitrogen gas) | Placebo comparator | Drug: Nitrogen GasPatients randomized to bioinert inhaled gas at OI 10-15. |
| Crossover iNO | Active comparator | Drug: Crossover iNOPatients who deteriorate (OI >20 on two consecutive blood gases) will be unblinded. If they are receiving placebo gas, they will be started on iNO and make up the crossover cohort. |
Who may qualify
- Ages
- 30 minutes to 48 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Gestational age ≥ 35 weeks gestation
- Age of life ≤ 48 hours
- Diagnosis of hypoxic respiratory failure (HRF) as defined by a post-ductal SaO2 ≤90% in ≥50% oxygen with a PEEP of ≥ 6cm or an oxygenation index (OI) ≥ 10 but ≤ 15 when mean airway pressure and PaO2 are known.
- Mothers (ages 18 - 65) of eligible subjects for additional data collection
Key exclusion criteria (8 listed)
- Gestational age < 35 weeks gestation.
- Post-natal age > 48 hours.
- Previous treatment with 100% oxygen for longer than 4 hours.
- Confirmed congenital diaphragmatic hernia.
- Suspected or confirmed congenital airway or pulmonary anomaly.
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: INOmaxDrug is initiated at 20ppm. Patients randomized to receive iNO at OI 10-15. | Drug | Early inhaled nitric oxide |
| Nitrogen GasAlso: bioinertPlacebo gas (bioinert), Patients randomized to bioinert inhaled gas at OI 10-15. | Drug | Bioinert inhaled gas (nitrogen gas) |
| Crossover iNOAlso: bioinert, INOmaxPatients who deteriorate (OI >20 on two consecutive blood gases) will be unblinded. If they are receiving placebo gas, they will be started on iNO and make up the crossover cohort. | Drug | Crossover iNO |
Primary outcome
Biomarkers of oxidative injury.
Time frame: Urine samples will be collected upon enrollment and then at specific time points within the first 48 hours of study intervention to compare the change in biomarker concentrations from baseline up to hour 48.
Early administration of iNO to infants with HRF will result in reduced hyperoxia-mediated oxidative injury as measured by known biomarkers of oxygen free radical injury, including malondialdehyde and 8-hydroxy-2'-deoxyguanosine.
5 secondary outcomes
Responsiveness to study treatment.
Time frame: Arterial oxygen concentration will be measured upon enrollment and at specific time points in the first 36 hours of study intervention to compare the change in arterial oxygen concentration from baseline up to hour 36.
Expression of endothelin-1.
Time frame: Concentration of endothelin-1 will be measured upon enrollment and at specific time points in the first 36 hours of study intervention to compare the change in concentration from baseline up to hour 36.
Markers of inflammation.
Time frame: Concentrations of pro and anti-inflammatory markers will be measured upon enrollment and at specific time points in the first 36 hours of study intervention to compare the change in concentrations from baseline up to hour 36.
Duration of oxygen treatment.
Time frame: Participants will be followed for the duration of their hospital stay, with an expected average stay of 4 weeks.
Expression of VEGF (vascular endothelial growth factor).
Time frame: Concentration of VEGF will be measured upon enrollment and at specific time points in the first 36 hours of study intervention to compare the change in concentration from baseline up to hour 36.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2020.
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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.
Catalina Bazacliu, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Inhaled nitric oxide, Nitrogen Gas and Crossover iNO in people with Persistent Fetal Circulation Syndrome and Hypertension, Pulmonary, of Newborn, Persistent, run by University of Florida 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 4 inclusion and 8 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: withdrawn, as of the sponsor's last update on 7 Jan 2020. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was withdrawn before enrolling participants, so there are no results.
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?
Biomarkers of oxidative injury. (time frame: Urine samples will be collected upon enrollment and then at specific time points within the first 48 hours of study intervention to compare the change in biomarker concentrations from baseline up to hour 48.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Jan 2020.