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

NCT02851472 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: FDA IND 126254
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Anemia

Keywords

TRAGI (transfusion related acute gut injury); inhaled nitric oxide (iNO); prematurity; PRBC transfusion; NEC (necrotizing enterocolitis); NIRS (near infrared spectroscopy); ELGAN (extremely low gestational age neonate)

Outcome Measures

Primary Outcomes (1)

• Increased NIRS oxygenation after a PRBC transfusion in iNO treated neonates vs Placebo

  The investigators hypothesize that NIRS signal will be significantly higher in the iNO treated group during the 2nd hour after transfusion is concluded vs Placebo. NIRS will be measured continuously and averaged every 5 minutes to create a single hourly point for each subject before and after the transfusion for statistical analysis.

  19 hours

Secondary Outcomes (1)

• Lower fractional tissue oxygen extraction (FTOE) in iNO treated neonates after PRBC transfusion vs Placebo

  19 hours

Study Arms (2)

Inhaled Nitric Oxide

EXPERIMENTAL

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

Drug: Inhaled Nitric Oxide

Placebo

ACTIVE COMPARATOR

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

Drug: Placebo

Interventions

Inhaled Nitric Oxide 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.

Also known as: iNO

Inhaled Nitric Oxide

Placebo 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.

Also known as: Control

Placebo

Eligibility Criteria

• Age: 2 Weeks+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• New York Medical College: lead
• Stony Brook University: collaborator
• Baystate Medical Center: collaborator
• East Carolina University: collaborator
• New York University: collaborator

Study Sites (4)

Baystate Children's Hospital

Springfield, Massachusetts, 01199, United States

RECRUITING

Stony Brook Children's Hospital

Stony Brook, New York, 11794, United States

SUSPENDED

Maria Fareri Childrens Hospital

Valhalla, New York, 10595, United States

RECRUITING

East Carolina University

Greenville, North Carolina, 27834, United States

RECRUITING

Related Publications (6)

• 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.

  PMID: 22818551 RESULT

• 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.

  PMID: 25104129 RESULT

• 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.

  PMID: 29906796 RESULT

• 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.

  PMID: 25927273 RESULT

• 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.

  PMID: 26340878 RESULT

• 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

  RESULT

MeSH Terms

Conditions

Anemia; Premature Birth; Enterocolitis, Necrotizing

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Edmund LaGamma, MD

  New York Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Edmund LaGamma, MD

CONTACT

914-493-8558; edmund_lagamma@nymc.edu

Gad Alpan, MD

CONTACT

914-493-8558; gad_alpan@nymc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Neonatology

Model Details: subjects are randomize into either of two groups: intervention or placebo

Study Record Dates

• First Submitted: July 20, 2016
• First Posted: August 1, 2016
• Study Start: February 6, 2019
• Primary Completion: February 5, 2021
• Study Completion: June 30, 2021
• Last Updated: April 24, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After publication of the primary manuscript
• Access Criteria: Data available if there is a well thought-out plan from a credible investigator who is exeprineced in neonatology, transfusion medicine or control of the microcirculation via nitric oxide.

Locations

US (4)