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

Anemia Clinical Trial

— iNO-TRAGI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02851472
• Other study ID #: FDA IND 126254
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 6, 2019
• Est. completion date: June 30, 2021

Study information

• Verified date: April 2019
• Source: New York Medical College
• Contact: Edmund LaGamma, MD
• Phone: 914-493-8558
• Email: edmund_lagamma[@]nymc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 30, 2021
• Est. primary completion date: February 5, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Anemia

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	East Carolina University	Greenville	North Carolina
United States	Baystate Children's Hospital	Springfield	Massachusetts
United States	Stony Brook Children's Hospital	Stony Brook	New York
United States	Maria Fareri Childrens Hospital	Valhalla	New York

Sponsors (5)

Lead Sponsor	Collaborator
New York Medical College	Baystate Medical Center, East Carolina University, New York University, Stony Brook University

Country where clinical trial is conducted

United States, 

References & 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. Review. — View Citation

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

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. — View Citation

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-1477 — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Lower fractional tissue oxygen extraction (FTOE) in iNO treated neonates after PRBC transfusion vs Placebo	FTOE will be calculated from the 5 minute epochs of the recorded pulse oximeter and NIRS devices. The investigators hypothesize that FTOE will be significantly lower (i.e. improved) in the iNO treated group during the 2nd hour after transfusion is concluded vs Placebo. One entire hour before and another after the transfusion will be combined for each patient for statistical analysis.	19 hours