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

Phase 1

• Conditions: Anemia
• Interventions: Drug: Inhaled Nitric Oxide; Drug: Placebo

• Registration Number: NCT02851472
• Lead Sponsor: New York Medical College

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.

Detailed 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

Study Timeline

• Study First Submitted: 2016-07-20
• Study First Submitted QC: 2016-07-29
• Study First Posted: 2016-08-01
• Study Start: 2019-02-06
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-22
• Last Update Posted: 2019-04-24
• Primary Completion: 2021-02-05
• Study Completion: 2021-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Inhaled Nitric Oxide	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
Placebo	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

Primary Outcome Measures

Name	Time	Method
Increased NIRS oxygenation after a PRBC transfusion in iNO treated neonates vs Placebo	19 hours	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.

Secondary Outcome Measures

Name	Time	Method
Lower fractional tissue oxygen extraction (FTOE) in iNO treated neonates after PRBC transfusion vs Placebo	19 hours	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.

Trial Locations

Locations (4)

Stony Brook Children's Hospital; 🇺🇸 Stony Brook, New York, United States

Maria Fareri Childrens Hospital; 🇺🇸 Valhalla, New York, United States

East Carolina University; 🇺🇸 Greenville, North Carolina, United States

Baystate Children's Hospital; 🇺🇸 Springfield, Massachusetts, United States