Clinical trial NCT02851472: Prevention of Transfusion Related Acute Gut Injury (TRAGI) in Extremely Low Gestational Age Neonates (ELGANs) Using iNO
Official title: Prevention of Transfusion Related Acute Gut Injury (TRAGI) in Extremely Low Gestational Age Neonates (ELGAN) Neonates Using iNO
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
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)
Lead sponsor: New York Medical College
Sponsor class: OTHER
Collaborators: name: Stony Brook University
name: Baystate Medical Center
name: East Carolina University
name: New York University
First posted: 2016-08-01
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: subjects are randomize into either of two groups: intervention or placebo
Primary purpose: TREATMENT

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

Eligibility criteria: 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)

Primary outcomes:
measure: Increased NIRS oxygenation after a PRBC transfusion in iNO treated neonates vs Placebo
timeFrame: 19 hours
Secondary outcomes:
measure: Lower fractional tissue oxygen extraction (FTOE) in iNO treated neonates after PRBC transfusion vs Placebo
timeFrame: 19 hours
Other outcomes:
Locations:
city: Springfield
country: United States
facility: Baystate Children's Hospital
state: Massachusetts
city: Stony Brook
country: United States
facility: Stony Brook Children's Hospital
state: New York
city: Valhalla
country: United States
facility: Maria Fareri Childrens Hospital
state: New York
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
Study officials:
affiliation: New York Medical College
name: Edmund LaGamma, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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-1477213.
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.
citation: 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.
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.
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