Respiratory Distress Syndrome in Premature InfantsiNONCT01220687
Inhaled Nitric Oxide (iNO) as an Adjunct to Neonatal Resuscitation
A study testing iNO and Nitrogen in people with Respiratory Distress Syndrome in Premature Infants and Very Low Birth Weight Baby, run by University of Oklahoma at 2 sites in United States.
Trial summary
This study hopes to determine whether nitric oxide along with oxygen during the first 20 minutes of life in infants needing help with breathing will reduce the percentage and total exposure to oxygen during that time frame. Read more about this study
- Who is it for?
- Ages 1 minute to 2 minutes
- Conditions the study is for
- Respiratory Distress Syndrome in Premature Infants, Very Low Birth Weight Baby
- What is being tested?
- iNO and Nitrogen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2011to 1 May 2017
- Phase
- Interventional
- 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 1 minute to 2 minutes
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants that are 25 0/7 - 31 6/7 weeks gestation
- Infants who require Continuous Positive Airway Pressure (CPAP) or Positive Pressure Ventilation ( PPV) during delivery room resuscitation.
Who cannot join
- Refusal of consent
- Known complex congenital anomalies of the heart or lungs
- Known major genetic defects
- Hydrops fetalis
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
University of Oklahoma, Childrens Hospital
Oklahoma City, Oklahoma, 73104
About this study
Official title: Administration of Inhaled Nitric Oxide (iNO) as an Adjunct to Neonatal Resuscitation Protocol: A Pilot Trial
This study hopes to determine whether nitric oxide along with oxygen during the first 20 minutes of life in infants needing help with breathing will reduce the percentage and total exposure to oxygen during that time frame. Although the use of oxygen in management of breathing is an important part of supporting baby immediately after delivery, there is more evidence that too much exposure to oxygen may lead to potential problems for your baby later. Oxygen exposure can be harmful to premature babies developing lungs.
Read the detailed description
Current Neonatal Resuscitation Program (NRP) guidelines suggest the use of supplemental oxygen up to fraction of inspired oxygen of 1.0 during neonatal resuscitation for both term and preterm newborns. Exposure to supplemental oxygen in preterm babies has been shown to have significant toxicity. Even minimal exposure in the first hours of life has been shown to be associated with morbidity including later onset of cancer. The transition from fetal circulation to neonatal circulation is a complex process requiring lung inflation and decrease in pulmonary vascular resistance. Endogenous nitric oxide, along with oxygen, plays a major role in facilitating this transition by decreasing pulmonary vascular resistance. It is not known whether exogenous nitric oxide would facilitate this transition. In this study, we propose a novel approach to resuscitation of preterm infants where inhaled nitric oxide (iNO) will be used as an adjunct to oxygen with the primary goal of reducing supplemental oxygen exposure. This study is designed to be a double-blind, randomized, -placebo- controlled pilot trial with strict monitoring of parameters during transition in the delivery room.
- Being tested
- iNO, Nitrogen
- Keywords
- Prematurity, Oxygen exposure, Nitric Oxide
- Medical subject headings
- Respiratory Distress Syndrome In Premature Infants, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iNODrug
Also called Inhaled Nitric Oxide
Immediately after birth, subjects will be randomized to receive iNO (20ppm) or nitrogen (placebo gas) with blended oxygen (starting with 0.3). Fraction of inspired oxygen will be adjusted by 0.1 increments every 15 seconds targeting pre-ductal oxygen saturation of 70-85% in the first 2 minutes of life, and then 85-93% until the end of the study period while requiring supplemental oxygen.
NitrogenOther
Subjects will be randomized to receive iNO (20ppm) or nitrogen (placebo gas) with blended oxygen (starting with 0.3). Fraction of inspired oxygen will be adjusted by 0.1 increments every 15 seconds targeting pre-ductal oxygen saturation of 70-85% in the first 2 minutes of life, and then 85-93% until the end of the study period while requiring supplemental oxygen.
| Study group | Role | What they receive |
|---|---|---|
| Placebo 20ppm | Placebo comparator | Nitrogen at 20 ppm at the beginning of study start with gradual taper at 10 minutes of the study and completely off by 17 minutes of the study Receives: Other: Nitrogen |
| Inhaled Nitric Oxide (iNO) 20 ppm | Experimental | Inhaled Nitric Oxide 20 ppm at the beginning of study start with gradual taper at 10 minutes of the study and completely off by 17 minutes of the study Receives: Drug: iNO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Factional Inspired Oxygen Percent (FiO2)
To investigate whether iNO decreases the supplemental oxygen exposure in the preterm infants who require continuous positive airway pressure (CPAP) or positive pressure ventilation (PPV) during resuscitation as per Neonatal Resuscitation Program (NRP) protocol.
Measured: 20 minutes
Rate of Hyperoxia
FiO2 >60% at any 5 second increment during the study period of 20 minutes for each infant in each arm.
Measured: 20 minutes
Pre and Postductal Saturation Levels
Oxygen saturations as described as preductal (right hand) as well as post ductal (either foot) and measured as percent of saturated hemoglobin by pulse oximetry.
Measured: at 20 minutes (end of study)
Heart Rate During Resuscitation
Measured and recorded heart rates every 5 seconds on study as described as beats per minute (BPM)
Measured: 5, 10 and 20 minutes on study
Need for Intubation
Infants requiring placement of endotracheal tube as part of the Neonatal Resuscitation Program algorithm for airway management.
Measured: by end of study, 20 minutes
Secondary outcomes (6)
Intraventricular Hemorrhage > Grade 2
Intraventricular Hemorrhage (IVH) > Gr 2 as described by radiographic scale as described in "Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm.", Papile L A; Burstein J; Burstein R; Koffler H, The Journal of pediatrics, (1978 Apr) Vol. 92, No. 4, pp. 529-34. Journal code: 0375410. ISSN: 0022-3476. L-ISSN: 0022-3476.
IVH classification systems Papile system Grade I Subependymal hemorrhage Grade II IVH without ventricular dilation Grade III IVH with ventricular dilation Grade IV Extensive IVH with parenchymal involvement
Measured: Hospital Discharge
Infants With Patent Ductus Arteriosus (PDA) Requiring Treatment
Count of patients requiring either pharmacologic or surgical treatment for persistent PDA
Measured: Prior to infant discharge from the hospital
Retinopathy of Prematurity (ROP)> Stage 2
Staging of any retinal disease as described by the standard screening by the American Association for Pediatric Ophthalmology and Strabismus. Only infants who survived to obtain retinal imaging are included (12 in Placebo arm and 11 in INO arm)
Measured: Prior to infant discharge from the hospital
Mechanical Ventilation, Non-invasive Ventilation (NIV), and Length of Stay in Days (LOS)
endotracheal or other airway placement and mechanical ventilation in days, days of non-invasive ventilation as described as nasal ventilation, CPAP, high flow and low flow oxygen as counted in days. Only infants who survived to discharge were included in this analysis.
Measured: Prior to infant discharge from the hospital
Bronchopulmonary Dysplasia
Bronchopulmonary Dysplasia as described as oxygen need at 36 weeks adjusted gestational age. Only infants who survived to 36 weeks gestation were included in this analysis.
Measured: at 36 weeks adjusted gestational age of participant
Late Onset Sepsis
Late Onset Sepsis as described as infection after day 5 of life. This would include all patients who survived to day of life 5.
Measured: at any time during study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2010 (estimated)
- Study startApr 2011
- Primary completionJan 2017
- Study completion1 May 2017
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.
- Other trials for Respiratory Distress Syndrome in Premature InfantsStudies of the same condition, open and under way.
- More trials run by University of OklahomaThe 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oklahoma
- Sponsor type
- University, hospital or other
- Collaborators
- Mallinckrodt
- Responsible party
- Sponsor
- Investigators
- Kris Sekar, M.D., Principal investigator, University of Oklahoma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01220687
- Sponsor's protocol ID
- 1976
- Acronym
- iNO
- Status last verified
- Aug 2020
- First submitted
- 7 Oct 2010
- Last updated
- 19 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Abstract presented to The Pediatric Academic Society Meeting, May 9, 2017
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of Inhaled Nitric Oxide (iNO) as an Adjunct to Neonatal Resuscitation Protocol: A Pilot Trial
- ClinicalTrials.gov ID
- NCT01220687
- Acronym / sponsor ID
- iNO / 1976
- Keywords
- Prematurity, Oxygen exposure, Nitric Oxide
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- University of OklahomaUniversity, hospital or other
- Collaborators
- Mallinckrodt
- Study start
- Apr 2011
- Primary completion
- Jan 2017 (actual)
- Study completion
- 1 May 2017 (actual)
- First posted
- 14 Oct 2010 (estimated)
- Results
- Posted 19 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study hopes to determine whether nitric oxide along with oxygen during the first 20 minutes of life in infants needing help with breathing will reduce the percentage and total exposure to oxygen during that time frame. Although the use of oxygen in management of breathing is an important part of supporting baby immediately after delivery, there is more evidence that too much exposure to oxygen may lead to potential problems for your baby later. Oxygen exposure can be harmful to premature babies developing lungs.
Detailed description
Current Neonatal Resuscitation Program (NRP) guidelines suggest the use of supplemental oxygen up to fraction of inspired oxygen of 1.0 during neonatal resuscitation for both term and preterm newborns. Exposure to supplemental oxygen in preterm babies has been shown to have significant toxicity. Even minimal exposure in the first hours of life has been shown to be associated with morbidity including later onset of cancer. The transition from fetal circulation to neonatal circulation is a complex process requiring lung inflation and decrease in pulmonary vascular resistance. Endogenous nitric oxide, along with oxygen, plays a major role in facilitating this transition by decreasing pulmonary vascular resistance. It is not known whether exogenous nitric oxide would facilitate this transition. In this study, we propose a novel approach to resuscitation of preterm infants where inhaled nitric oxide (iNO) will be used as an adjunct to oxygen with the primary goal of reducing supplemental oxygen exposure. This study is designed to be a double-blind, randomized, -placebo- controlled pilot trial with strict monitoring of parameters during transition in the delivery room.
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 |
|---|---|---|
| Placebo 20ppm | Placebo comparator | Other: NitrogenNitrogen at 20 ppm at the beginning of study start with gradual taper at 10 minutes of the study and completely off by 17 minutes of the study |
| Inhaled Nitric Oxide (iNO) 20 ppm | Experimental | Drug: iNOInhaled Nitric Oxide 20 ppm at the beginning of study start with gradual taper at 10 minutes of the study and completely off by 17 minutes of the study |
Who may qualify
- Ages
- 1 minute to 2 minutes
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Infants that are 25 0/7 - 31 6/7 weeks gestation
- Infants who require Continuous Positive Airway Pressure (CPAP) or Positive Pressure Ventilation ( PPV) during delivery room resuscitation.
Key exclusion criteria (4 listed)
- Refusal of consent
- Known complex congenital anomalies of the heart or lungs
- Known major genetic defects
- Hydrops fetalis
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 |
|---|---|---|
| iNOAlso: Inhaled Nitric OxideImmediately after birth, subjects will be randomized to receive iNO (20ppm) or nitrogen (placebo gas) with blended oxygen (starting with 0.3). Fraction of inspired oxygen will be adjusted by 0.1 increments every 15 seconds targeting pre-ductal oxygen saturation of 70-85% in the first 2 minutes of life, and then 85-93% until the end of the study period while requiring supplemental oxygen. | Drug | Inhaled Nitric Oxide (iNO) 20 ppm |
| NitrogenSubjects will be randomized to receive iNO (20ppm) or nitrogen (placebo gas) with blended oxygen (starting with 0.3). Fraction of inspired oxygen will be adjusted by 0.1 increments every 15 seconds targeting pre-ductal oxygen saturation of 70-85% in the first 2 minutes of life, and then 85-93% until the end of the study period while requiring supplemental oxygen. | Other | Placebo 20ppm |
Primary outcome
Maximum Factional Inspired Oxygen Percent (FiO2)
Time frame: 20 minutes
To investigate whether iNO decreases the supplemental oxygen exposure in the preterm infants who require continuous positive airway pressure (CPAP) or positive pressure ventilation (PPV) during resuscitation as per Neonatal Resuscitation Program (NRP) protocol.
Rate of Hyperoxia
Time frame: 20 minutes
FiO2 >60% at any 5 second increment during the study period of 20 minutes for each infant in each arm.
Pre and Postductal Saturation Levels
Time frame: at 20 minutes (end of study)
Oxygen saturations as described as preductal (right hand) as well as post ductal (either foot) and measured as percent of saturated hemoglobin by pulse oximetry.
Heart Rate During Resuscitation
Time frame: 5, 10 and 20 minutes on study
Measured and recorded heart rates every 5 seconds on study as described as beats per minute (BPM)
Need for Intubation
Time frame: by end of study, 20 minutes
Infants requiring placement of endotracheal tube as part of the Neonatal Resuscitation Program algorithm for airway management.
6 secondary outcomes
Intraventricular Hemorrhage > Grade 2
Time frame: Hospital Discharge
Infants With Patent Ductus Arteriosus (PDA) Requiring Treatment
Time frame: Prior to infant discharge from the hospital
Retinopathy of Prematurity (ROP)> Stage 2
Time frame: Prior to infant discharge from the hospital
Mechanical Ventilation, Non-invasive Ventilation (NIV), and Length of Stay in Days (LOS)
Time frame: Prior to infant discharge from the hospital
Bronchopulmonary Dysplasia
Time frame: at 36 weeks adjusted gestational age of participant
Late Onset Sepsis
Time frame: at any time during study period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Abstract presented to The Pediatric Academic Society Meeting, May 9, 2017
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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.
Kris Sekar, M.D. principal investigator
University of Oklahoma
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing iNO and Nitrogen in people with Respiratory Distress Syndrome in Premature Infants and Very Low Birth Weight Baby, run by University of Oklahoma at 2 sites 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 2 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: finished, as of the sponsor's last update on 19 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Aug 2020). 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?
Maximum Factional Inspired Oxygen Percent (FiO2) (time frame: 20 minutes). The study lists 5 primary outcomes in all. 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 19 Aug 2020.