Ischemia/Reperfusion Injury After Neonatal Cardiac SurgeryNCT02151877

Efficacy of Nitric Oxide Administration in Attenuating Ischemia/Reperfusion Injury During Neonatal Cardiopulmonary Bypass

A study testing Inhaled Nitric Oxide in people with Ischemia/Reperfusion Injury After Neonatal Cardiac Surgery and Inflammatory Reaction After Neonatal Cardiac Surgery, run by Wake Forest University Health Sciences at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 1 day to 30 days
Conditions the study is for: Ischemia/Reperfusion Injury After Neonatal Cardiac Surgery, Inflammatory Reaction After Neonatal Cardiac Surgery
What is being tested?: Inhaled Nitric Oxide
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 24 participants
Where: 1 siteUnited States
Study dates: Jul 2014to 15 Aug 2018
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 day to 30 days
All sexes
No healthy volunteers
Child

Who may be able to join

Neonates, age 0-30 days
Full term, > 37 weeks gestation
Birth weight ≥ 2.6 kg

Who cannot join

Preoperative sepsis
Preoperative renal dysfunction
Preoperative intracranial hemorrhage
Chromosomal abnormalities and/or genetic syndromes
Prior intervention (catheter based or surgical)

Trial locations and contacts

1 site in 1 country.

United States1 site

Advocate Children's Hospital
Oak Lawn, Illinois, 60453

Other trials in United States

About this study

Official title: Efficacy of Nitric Oxide Administration in Attenuating Ischemia/Reperfusion Injury During Neonatal Cardiopulmonary Bypass.

Around 7500 neonates born yearly in the United States have complex congenital heart disease that require surgical repair in the first few days of life. The complexity of the surgical repair requires long periods of cardiopulmonary bypass (CPB) and the use of intermittent periods of low flow or complete circulatory arrest. The immature neonatal vital organs are more prone to the complications of the cardiopulmonary bypass circulation, namely ischemia/reperfusion (I/R) injury and systemic inflammatory response. Inhaled nitric oxide (NO) is used frequently in neonates for the treatment of pulmonary hypertension, Additionally, many studies have shown that NO has an anti-inflammatory effect by reducing I/R injury and endothelial dysfunction.

The purpose of this pilot study is to assess the efficacy of NO administration via the CPB circuit in attenuating the CPB induced I/R injury and systemic inflammatory reaction in neonates undergoing repair of complex congenital heart defects. Specific goals will be to demonstrate that NO use via CPB will:

Decrease markers of I/R injury and systemic inflammatory response.
Decrease platelet activation leading to reduced postoperative bleeding and transfusion requirements.
Decrease postoperative organ dysfunction, and hence decrease operative mortality and postoperative morbidity.

Twelve neonates undergoing repair of complex congenital heart defects will receive NO via the CPB circuit, for the duration of surgery. They will be compared to a control group of 12 similar patients. Serum levels of different ischemic reperfusion injury and inflammatory markers will be measured at different time points after surgery and will be correlated with different end organ function tests and clinical course in the postoperative period. The results will be compared between the two groups to try to determine the clinical benefit of NO administration through CPB circuit.

Conditions: Ischemia/Reperfusion Injury After Neonatal Cardiac Surgery, Inflammatory Reaction After Neonatal Cardiac Surgery
Being tested: Inhaled Nitric Oxide, placebo
Keywords: Ischemia/reperfusion injury
Medical subject headings: Ischemia, Reperfusion Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Inhaled Nitric OxideDrug
Also called study group
delivering inhaled Nitric Oxide into the cardiopulmonary bypass circuit during neonatal cardiac surgery
placeboDrug
Also called control group
inhaled Nitric Oxide not delivered to the cardiopulmonary bypass circuit during neonatal cardiac surgery

Study groups in NCT02151877
Study group	Role	What they receive
Nitric oxide on CPB	Experimental	neonates receiving inhaled NO into the cardiopulmonary bypass circuit during cardiac surgery Receives: Drug: Inhaled Nitric Oxide
control	Placebo comparator	neonates not receiving inhaled NO into the cardiopulmonary bypass Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op)
The primary study endpoints are to evaluate whether NO delivered through the neonatal cardiopulmonary bypass (CPB) circuit can decrease various biochemical markers of ischemia/reperfusion injury and oxidative damage. Markers to be analyzed will include cardiac troponin I, interleukins (IL), tumor necrosis factor, N-terminal prohormone for brain natriuretic peptide (NT-proBNP),lactate dehydrogenase (LDH), plasma anti-oxidant levels, plasma malondialdehyde (MDA) levels.
Measured: Pre-op baseline and up to 12 hours after surgery

Secondary outcomes (4)

Total Fluid Balance at 48 Hours
The secondary study endpoints are to evaluate whether NO delivered through the neonatal CPB circuit can decrease the clinical signs of ischemia/reperfusion injury and/or cardiac dysfunction. Clinical parameters (post surgery) include inotropic support, fluid balances, diuretic support, ventilator times, and length of ICU stay will be evaluated.
Measured: 48 hours post surgery
Time Until Start of Diuretic Therapy
hours until start of diuretic therapy
Measured: Pre-op to 72 hours post surgery
Inotropic Score Day 1
The Inotropic Score is an objective clinical tool used to quantify the need for cardiovascular support in children and adolescents after surgery and to predict prognosis of pediatric septic shock (higher score predicts higher risk or worse prognosis).The Inotropic Score is low if <= 20, intermediate if 21-30, and high if > 30.
Formula used in the study:
Daily inotropic score (mcg/kg/min) = Dopamine drip dose+ dobutamine drip dose+ (milrinone drip dose times 10) + (epinephrine drip dose times 100 )
Measured: 24 hours post surgery
Length of Intubation and PSHU Stay
Days to extubation and Pediatric Surgical Heart Unit (PSHU) length of stay (LOS) as measuring patient surgical outcomes.
Measured: Surgery to discharge

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 201415 Aug 2018

First posted2 Jun 2014 (estimated)
Study startJul 2014
Primary completion15 Aug 2018
Study completion15 Aug 2018

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 Ischemia/Reperfusion Injury After Neonatal Cardiac SurgeryStudies of the same condition, open and under way.
More trials run by Wake Forest University Health SciencesThe 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: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02151877
Sponsor's protocol ID: K5900209
Status last verified: Oct 2024
First submitted: 27 May 2014
Last updated: 8 Oct 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 8 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Efficacy of Nitric Oxide Administration in Attenuating Ischemia/Reperfusion Injury During Neonatal Cardiopulmonary Bypass.
ClinicalTrials.gov ID: NCT02151877
Acronym / sponsor ID: K5900209
Conditions: Ischemia/Reperfusion Injury After Neonatal Cardiac Surgery, Inflammatory Reaction After Neonatal Cardiac Surgery
Keywords: Ischemia/reperfusion injury
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: Wake Forest University Health SciencesUniversity, hospital or other
Collaborators: Mallinckrodt
Study start: Jul 2014
Primary completion: 15 Aug 2018 (actual)
Study completion: 15 Aug 2018 (actual)
First posted: 2 Jun 2014 (estimated)
Results: Posted 3 Apr 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Decrease markers of I/R injury and systemic inflammatory response.
Decrease platelet activation leading to reduced postoperative bleeding and transfusion requirements.
Decrease postoperative organ dysfunction, and hence decrease operative mortality and postoperative morbidity.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Nitric oxide on CPB	Experimental	Drug: Inhaled Nitric Oxideneonates receiving inhaled NO into the cardiopulmonary bypass circuit during cardiac surgery
control	Placebo comparator	Drug: placeboneonates not receiving inhaled NO into the cardiopulmonary bypass

Who may qualify

Ages: 1 day to 30 days
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (3 listed)

Neonates, age 0-30 days
Full term, > 37 weeks gestation
Birth weight ≥ 2.6 kg

Key exclusion criteria (5 listed)

Preoperative sepsis
Preoperative renal dysfunction
Preoperative intracranial hemorrhage
Chromosomal abnormalities and/or genetic syndromes
Prior intervention (catheter based or surgical)

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: study groupdelivering inhaled Nitric Oxide into the cardiopulmonary bypass circuit during neonatal cardiac surgery	Drug	Nitric oxide on CPB
placeboAlso: control groupinhaled Nitric Oxide not delivered to the cardiopulmonary bypass circuit during neonatal cardiac surgery	Drug	control

Primary outcome

Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op)
Time frame: Pre-op baseline and up to 12 hours after surgery
The primary study endpoints are to evaluate whether NO delivered through the neonatal cardiopulmonary bypass (CPB) circuit can decrease various biochemical markers of ischemia/reperfusion injury and oxidative damage. Markers to be analyzed will include cardiac troponin I, interleukins (IL), tumor necrosis factor, N-terminal prohormone for brain natriuretic peptide (NT-proBNP),lactate dehydrogenase (LDH), plasma anti-oxidant levels, plasma malondialdehyde (MDA) levels.

4 secondary outcomes

Total Fluid Balance at 48 Hours
Time frame: 48 hours post surgery
Time Until Start of Diuretic Therapy
Time frame: Pre-op to 72 hours post surgery
Inotropic Score Day 1
Time frame: 24 hours post surgery
Length of Intubation and PSHU Stay
Time frame: Surgery to discharge

Results and safety

Results posted to the registry on 3 Apr 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Nitric Oxide on CPB	12	12
Control	12	12

Primary outcome: Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op)

Time frame: Pre-op baseline and up to 12 hours after surgery. Mean (Standard Deviation). Unit: ng/ml

Measure	Nitric Oxide on CPB n = 12	Control n = 12
cardiac troponin I change	0.46 (0.55)	0.64 (0.64)
IL-6 change	11.52 (12.98)	26.98 (27.67)
IL-8 change	49.36 (42.86)	68.46 (81.09)
TNF alpha change	0.03 (0.20)	-0.12 (0.21)
NT pro-BNP change	7.03 (22.84)	1.51 (2.29)
LDH change	48.85 (117.39)	53.44 (73.58)
Superoxide Dismutase change	-0.04 (0.04)	-0.05 (0.06)
Plasma MDA change	7.61 (12.90)	10.65 (14.99)

Nitric Oxide on CPB vs Control: p >0.05, t-test, 2 sided

Population analysed: Intent to treat (ITT)

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events (AEs) were collected for the entire hospitalization period, from surgical date to 104 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Nitric Oxide on CPB	0 of 12 (0%)	2 of 12 (16.7%)	0 of 12
Control	0 of 12 (0%)	1 of 12 (8.3%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: No

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.

Chawki F Elzein, MD principal investigator

Advocate Healthcare

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 5 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 8 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Apr 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?

Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op) (time frame: Pre-op baseline and up to 12 hours after surgery). 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 NCT02151877.

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 8 Oct 2024.