Prevention of Transfusion Related Acute Gut Injury (TRAGI) in Extremely Low Gestational Age Neonates (ELGANs) Using iNO

NCT ID: NCT02851472

Last Updated: 2019-04-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-06

Study Completion Date

2021-06-30

Brief Summary

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The investigators seek to determine whether providing inhaled nitric oxide (iNO; a vasodilator) will improve the delivery of oxygen to the brain, kidney and intestines of preterm neonates during and after the subject receives a packed red blood cell transfusion (PRBC) for anemia vs. baseline period. The investigators will observe the effect of inhaled nitric oxide vs. placebo at these body sites to determine whether iNO will alter the fractional tissue oxygen extraction. Treatment and control groups will be compared to each other at equivalent epochs as will individual patients before, during and after the PRBC transfusion.

Detailed Description

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Selection criteria: 1) Neonates 24 0/7 to 27 6/7 weeks gestational age (GA) 2) More than 2 weeks postnatal age. 3) Anemia with Hct less than 28 % 4) \>50 % total daily fluids is enteral 5) History of at least 1 prior PRBC transfusion ELGANs admitted to the neonatal intensive care unit (NICU) will be screened for the study. If patients meet the selection criteria, parents will be approached to obtain informed consent. Then the patient will be randomized to either iNO or placebo group before treatment. The treating physician will make the decision regarding timing of the PRBC transfusion to treat anemia for the subject.

During the period of observation, near infrared spectroscopy (NIRS) monitoring will be performed on all enrolled subjects during which a non-invasive probe will be attached to the skin at 3 sites simultaneously- on abdomen below umbilicus, flank/back, and forehead for calculation of fractional tissue oxygen extraction ( FTOE) in conjunction with concurrent pulse oximetry recordings.

Conventional vital signs, blood gas, lactate, haptoglobin and cytokines will be measured before and after the PRBC transfusion

Conditions

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Anemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

subjects are randomize into either of two groups: intervention or placebo
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
iNO vs nitrogen will be administered from tanks labeled with a code number that is known by the manufacturer and a campus safety officer but masked to investigators and to bedside personnel.

Study Groups

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Inhaled Nitric Oxide

iNO will be given at 20 ppm, continuous, via inhalation before (1 hour), during (3 hours) and after (2 hours) elective blood transfusion and NIRS monitoring

Group Type EXPERIMENTAL

Inhaled Nitric Oxide

Intervention Type DRUG

Nitric oxide gas will be added to the inhaled gas mixture that the patient was already receiving at baseline, using standard of care gas delivery systems adapted specifically for this study.

Placebo

Placebo gas (nitrogen) will be given continuous, via inhalation at the same ppm, before (1 hour), during (3 hours) and after (2 hours) elective blood transfusion and NIRS monitoring

Group Type ACTIVE_COMPARATOR

Placebo

Intervention Type DRUG

Placebo gas (nitrogen) will be added to the inhaled gas mixture that the patient was already receiving at baseline, using standard of care gas delivery systems specifically adapted for this study.

Interventions

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Inhaled Nitric Oxide

Nitric oxide gas will be added to the inhaled gas mixture that the patient was already receiving at baseline, using standard of care gas delivery systems adapted specifically for this study.

Intervention Type DRUG

Placebo

Placebo gas (nitrogen) will be added to the inhaled gas mixture that the patient was already receiving at baseline, using standard of care gas delivery systems specifically adapted for this study.

Intervention Type DRUG

Other Intervention Names

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iNO Control

Eligibility Criteria

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Inclusion Criteria

* Neonates 24 0/7 to 27 6/7 weeks gestational age
* More than 2 weeks postnatal age.
* Anemia with hematocrit (Hct) less than 28 %
* More than 50 % total daily fluids is enteral
* History of at least 1 prior PRBC transfusion (preferably same donor)

Exclusion Criteria

* Prior history of necrotizing enterocolitis (NEC) to avoid a confounder
* Clinically significant patent ductus arteriosus (PDA) requiring treatment (Rx) within 24h
* Hypotensive for age or active bleeding
* \< 50% of total fluids are enteral (breast milk or formula)
* Major congenital or surgical malformations
* Known chromosomal anomalies detected by antepartum testing or direct physical examination with subsequent postnatal laboratory confirmation
* Absence of parental or treating physician consent
* A concurrent randomized clinical trial (RCT) with another randomized drug
* Death expected \< 48h
* Another major concern by the treating physician that either mandates or prohibits study treatment such as known adverse reaction to prior transfusion (Tx)
Minimum Eligible Age

2 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stony Brook University

OTHER

Sponsor Role collaborator

Baystate Medical Center

OTHER

Sponsor Role collaborator

East Carolina University

OTHER

Sponsor Role collaborator

New York University

OTHER

Sponsor Role collaborator

New York Medical College

OTHER

Sponsor Role lead

Responsible Party

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Edmund LaGamma

Chief of Neonatology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Edmund LaGamma, MD

Role: PRINCIPAL_INVESTIGATOR

New York Medical College

Locations

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Baystate Children's Hospital

Springfield, Massachusetts, United States

Site Status RECRUITING

Stony Brook Children's Hospital

Stony Brook, New York, United States

Site Status SUSPENDED

Maria Fareri Childrens Hospital

Valhalla, New York, United States

Site Status RECRUITING

East Carolina University

Greenville, North Carolina, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Edmund LaGamma, MD

Role: CONTACT

914-493-8558

Gad Alpan, MD

Role: CONTACT

914-493-8558

Facility Contacts

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Rachana Singh, MD

Role: primary

413-794-2207

Ed LaGamma, MD

Role: primary

914-493-8558

Gad Alpan, MD

Role: backup

914 493 8558

Uduak Akpan, MD

Role: primary

252-744-1111

References

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La Gamma EF, Blau J. Transfusion-related acute gut injury: feeding, flora, flow, and barrier defense. Semin Perinatol. 2012 Aug;36(4):294-305. doi: 10.1053/j.semperi.2012.04.011.

Reference Type RESULT
PMID: 22818551 (View on PubMed)

Mintzer JP, Parvez B, Chelala M, Alpan G, LaGamma EF. Monitoring regional tissue oxygen extraction in neonates <1250 g helps identify transfusion thresholds independent of hematocrit. J Neonatal Perinatal Med. 2014 Jan 1;7(2):89-100. doi: 10.3233/NPM-1477213.

Reference Type RESULT
PMID: 25104129 (View on PubMed)

Mintzer JP, Parvez B, La Gamma EF. Regional Tissue Oxygen Extraction and Severity of Anemia in Very Low Birth Weight Neonates: A Pilot NIRS Analysis. Am J Perinatol. 2018 Dec;35(14):1411-1418. doi: 10.1055/s-0038-1660458. Epub 2018 Jun 15.

Reference Type RESULT
PMID: 29906796 (View on PubMed)

Mintzer JP, Parvez B, Alpan G, LaGamma EF. Effects of sodium bicarbonate correction of metabolic acidosis on regional tissue oxygenation in very low birth weight neonates. J Perinatol. 2015 Aug;35(8):601-6. doi: 10.1038/jp.2015.37. Epub 2015 Apr 30.

Reference Type RESULT
PMID: 25927273 (View on PubMed)

Mintzer JP, Parvez B, La Gamma EF. Umbilical Arterial Blood Sampling Alters Cerebral Tissue Oxygenation in Very Low Birth Weight Neonates. J Pediatr. 2015 Nov;167(5):1013-7. doi: 10.1016/j.jpeds.2015.08.016. Epub 2015 Sep 1.

Reference Type RESULT
PMID: 26340878 (View on PubMed)

LaGamma, EF, Feldman, A, Mintzer, J, Lakshminrusimha, S, Alpan, G. Red Blood Cell Storage in Transfusion-Related Acute Gut Injury. NeoReviews 16 (7): e420-e430, 2015

Reference Type RESULT

Other Identifiers

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FDA IND 126254

Identifier Type: -

Identifier Source: org_study_id

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