Back to results

Early iNO for Oxidative Stress, Vascular Tone and Inflammation in Babies With Hypoxic Respiratory Failure

Primary Purpose

Persistent Fetal Circulation Syndrome, Hypertension, Pulmonary, of Newborn, Persistent, Persistent Pulmonary Hypertension of Newborn

Status

Withdrawn

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Inhaled nitric oxide

Nitrogen Gas

Crossover iNO

About this trial

This is an interventional treatment trial for Persistent Fetal Circulation Syndrome focused on measuring Persistent Fetal Circulation Syndrome, Infant, Newborn, Nitric Oxide, Oxidative Stress, Endothelin 1, Vascular Endothelial Growth Factor

Eligibility Criteria

30 Minutes - 48 Hours (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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.

Sites / Locations

Shands Hospital at the University of Florida

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Active Comparator

Arm Label

Early inhaled nitric oxide

Bioinert inhaled gas (nitrogen gas)

Crossover iNO

Arm Description

Patients randomized to receive iNO at OI 10-15.

Patients randomized to bioinert inhaled gas at OI 10-15.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Expression of endothelin-1.

Earlier treatment with iNO may potentiate pulmonary vasodilation by modulating endothelin-1 expression.

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.

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.

Expression of VEGF (vascular endothelial growth factor).

Earlier treatment with iNO may potentiate pulmonary vasodilation by preventing hyperoxic down regulation of VEGF.

Full Information

NCT ID

NCT01891500

First Posted

June 19, 2013

Last Updated

January 5, 2020

Sponsor

University of Florida

Collaborators

Mallinckrodt

1. Study Identification

Unique Protocol Identification Number

NCT01891500

Brief Title

Early iNO for Oxidative Stress, Vascular Tone and Inflammation in Babies With Hypoxic Respiratory Failure

Official Title

Effect of Early iNO on Oxidative Stress, Vascular Tone and Inflammation in Term and Late-Preterm Infants With Hypoxic Respiratory Failure

Study Type

Interventional

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Withdrawn

Why Stopped

Difficult to identify subjects who meet enrollment criteria.

Study Start Date

May 2016 (Actual)

Primary Completion Date

September 18, 2019 (Actual)

Study Completion Date

September 19, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Florida

Collaborators

Mallinckrodt

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Early inhaled nitric oxide

Arm Type

Experimental

Arm Description

Patients randomized to receive iNO at OI 10-15.

Arm Title

Bioinert inhaled gas (nitrogen gas)

Arm Type

Placebo Comparator

Arm Description

Patients randomized to bioinert inhaled gas at OI 10-15.

Arm Title

Crossover iNO

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Inhaled nitric oxide

Other Intervention Name(s)

INOmax

Intervention Description

Drug is initiated at 20ppm. Patients randomized to receive iNO at OI 10-15.

Intervention Type

Drug

Intervention Name(s)

Nitrogen Gas

Other Intervention Name(s)

bioinert

Intervention Description

Placebo gas (bioinert), Patients randomized to bioinert inhaled gas at OI 10-15.

Intervention Type

Drug

Intervention Name(s)

Crossover iNO

Other Intervention Name(s)

bioinert, INOmax

Intervention Description

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.

Primary Outcome Measure Information:

Title

Biomarkers of oxidative injury.

Description

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.

Secondary Outcome Measure Information:

Title

Responsiveness to study treatment.

Description

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.

Title

Expression of endothelin-1.

Description

Earlier treatment with iNO may potentiate pulmonary vasodilation by modulating endothelin-1 expression.

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.

Title

Markers of inflammation.

Description

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.

Title

Duration of oxygen treatment.

Description

Early administration of iNO to infants with HRF will result in at least a 15% reduction in total days of oxygen therapy.

Time Frame

Participants will be followed for the duration of their hospital stay, with an expected average stay of 4 weeks.

Title

Expression of VEGF (vascular endothelial growth factor).

Description

Earlier treatment with iNO may potentiate pulmonary vasodilation by preventing hyperoxic down regulation of VEGF.

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Minutes

Maximum Age & Unit of Time

48 Hours

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Catalina Bazacliu, MD

Organizational Affiliation

University of Florida

Official's Role

Principal Investigator

Facility Information:

Facility Name

Shands Hospital at the University of Florida

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32610

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Early iNO for Oxidative Stress, Vascular Tone and Inflammation in Babies With Hypoxic Respiratory Failure

We'll reach out to this number within 24 hrs