umBilical Or Adult Donor Red Blood Cells in Extremely Low Gestational Age Neonates and Retinopathy of Prematurity (BORN)

NCT05100212 | Completed Phase 2

• 1 other identifier: 4364
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 10

Brief Summary

Extremely low gestational age neonates (ELGAN, i.e., born before 28 gestation weeks) are among the most heavily transfused pediatric patients. In this clinical setting, repeated red blood cell (RBC) transfusions independently predict a poor outcome, with a higher risk for mortality and morbidity. Recent studies from our own and other groups highlighted a close association between low levels of fetal hemoglobin (HbF) and severity of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD), two disabilities that frequently complicate preterm birth. This association is not surprising, considering that 1) preterm neonates have a highly immature antioxidant reserve and both ROP and BPD rely on the oxidative damage as underlying mechanism; 2) in comparison with HbA, HbF is endowed with higher oxygen affinity, greater redox potential, higher tetrameric stability, and higher ability to generate unbound nitric oxide, all functions potentially protective in presence of an oxidative challenge; 3) in normal prenatal life, developing organ and tissues are exposed exclusively to HbF until last weeks of gestation; 4) in preterm neonates, the switch of the synthesis from HbF to HbA occurs around their due date, i.e., several weeks after the premature birth; 5) when preterm neonates receive transfusions, their tissues are abruptly exposed to high levels of HbA. We have recently run a pilot trial demonstrating as a proof-of-concept that transfusing cord blood red blood cell concentrates (CB-RBC) effectively prevents or restrains the HbF loss consequent to adult donor standard transfusions (A-RBC). This study explores the hypothesis that transfusing CB-RBCs instead of A-RBC may lower the incidence of severe ROP in ELGANs needing transfusions.

Conditions

Retinopathy of Prematurity

Outcome Measures

Primary Outcomes (1)

• Retinopathy of prematurity

  Incidence of severe ROP (stage 3 and higher) in CB-RBC and A-RBC arms

  up to the age of 40 weeks

Study Arms (2)

Adult-RBC transfusions

ACTIVE COMPARATOR

Adult-red blood cell concentrate transfusions

Biological: adult donor RBC concentrates

CB-RBC transfusions

EXPERIMENTAL

Cord blood-red blood cell concentrate transfusions

Biological: cord blood-RBC concentrates

Interventions

cord blood-RBC concentrates BIOLOGICAL

Patients in the experimental arm are candidates to receive CB-RBC units until the completion of 29 weeks of postmenstrual age (29+6). In case of unavailability of an ABO/Rh matched CB-RBC unit, patients receive adult -RBC (standard transfusions).

Also known as: cord blood packed RBC

CB-RBC transfusions

adult donor RBC concentrates BIOLOGICAL

Patients in the comparator arm are candidates to receive adult donor-RBC units

Also known as: adult donor packed RBC

Adult-RBC transfusions

Eligibility Criteria

• Age: 24 Weeks - 27 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• gestational age (GA) at birth between 24+0 and 27+6 weeks
• signed informed consent of parents.

You may not qualify if:

• One or more of the following:
• maternal-fetal immunization
• hydrops fetalis
• major congenital malformations associated or not with genetic syndromes
• previous transfusions
• hemorrhage at birth
• congenital infections
• health care team deeming it inappropriate to approach the infant's family for informed consent.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead
• Fresenius Kabi: collaborator

Study Sites (10)

Azienda Ospedaliero Universitaria Careggi

Florence, Italy

Location

Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo,

Foggia, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Italy

Location

Ospedale Evangelico Villa Betania

Naples, Italy

Location

AORN Santobono-Pausilipon

Napoli, Italy

Location

Fondazione IRCCS Policlinico S. Matteo

Pavia, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, Italy

Location

Azienda Ospedaliera Bianchi Melacrino Morelli

Reggio Calabria, Italy

Location

Fondazione Policlinico Universitario A.Gemelli IRCCS

Rome, 00168, Italy

Location

Città della Salute e della Scienza

Torino, Italy

Location

Related Publications (2)

• Teofili L, Papacci P, Dani C, Cresi F, Remaschi G, Pellegrino C, Bianchi M, Ansaldi G, Campagnoli MF, Vania B, Lepore D, Franco FGS, Fabbri M, de Vera d' Aragona RP, Molisso A, Beccastrini E, Dragonetti A, Orazi L, Pasciuto T, Mozzetta I, Baldascino A, Locatelli E, Valentini CG, Giannantonio C, Carducci B, Gabbriellini S, Albiani R, Ciabatti E, Nicolotti N, Baroni S, Mazzoni A, Besso FG, Serrao F, Purcaro V, Coscia A, Pizzolo R, Raffaeli G, Villa S, Mondello I, Trimarchi A, Beccia F, Ghirardello S, Vento G. Cord blood transfusions in extremely low gestational age neonates to reduce severe retinopathy of prematurity: results of a prespecified interim analysis of the randomized BORN trial. Ital J Pediatr. 2024 Aug 7;50(1):142. doi: 10.1186/s13052-024-01714-w.

  PMID: 39113069 DERIVED

• Teofili L, Papacci P, Orlando N, Bianchi M, Pasciuto T, Mozzetta I, Palluzzi F, Giaco L, Giannantonio C, Remaschi G, Santosuosso M, Beccastrini E, Fabbri M, Valentini CG, Bonfini T, Cloclite E, Accorsi P, Dragonetti A, Cresi F, Ansaldi G, Raffaeli G, Villa S, Pucci G, Mondello I, Santodirocco M, Ghirardello S, Vento G. BORN study: a multicenter randomized trial investigating cord blood red blood cell transfusions to reduce the severity of retinopathy of prematurity in extremely low gestational age neonates. Trials. 2022 Dec 13;23(1):1010. doi: 10.1186/s13063-022-06949-8.

  PMID: 36514106 DERIVED

MeSH Terms

Conditions

Retinopathy of Prematurity

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Luciana Teofili, MD

  Fondazione Policlinico Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Interventional, randomized, controlled, double-blind, with an adaptive design to evaluate safety and efficacy of allogeneic CB-RBC transfusions.

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: October 29, 2021
• Study Start: December 1, 2021
• Primary Completion: January 15, 2025
• Study Completion: January 15, 2025
• Last Updated: February 27, 2025

Record last verified: 2024-10

Locations

IT (10)