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

NCT ID: NCT05100212

Last Updated: 2025-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-01
• Study Completion Date: 2025-01-15

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Adult-RBC transfusions

Adult-red blood cell concentrate transfusions

Group Type: ACTIVE_COMPARATOR

adult donor RBC concentrates

Intervention Type: BIOLOGICAL

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

CB-RBC transfusions

Cord blood-red blood cell concentrate transfusions

Group Type: EXPERIMENTAL

cord blood-RBC concentrates

Intervention Type: 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).

Interventions

cord blood-RBC concentrates

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).

Intervention Type: BIOLOGICAL

adult donor RBC concentrates

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

Intervention Type: BIOLOGICAL

Other Intervention Names

cord blood packed RBC; adult donor packed RBC

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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.

• Minimum Eligible Age: 24 Weeks
• Maximum Eligible Age: 27 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fresenius Kabi

INDUSTRY

Sponsor Role: collaborator

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luciana Teofili, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico Gemelli IRCCS

Locations

Azienda Ospedaliero Universitaria Careggi

Florence, , Italy

Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo,

Foggia, , Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Ospedale Evangelico Villa Betania

Naples, , Italy

AORN Santobono-Pausilipon

Napoli, , Italy

Fondazione IRCCS Policlinico S. Matteo

Pavia, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Azienda Ospedaliera Bianchi Melacrino Morelli

Reggio Calabria, , Italy

Fondazione Policlinico Universitario A.Gemelli IRCCS

Rome, , Italy

Città della Salute e della Scienza

Torino, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 39113069 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36514106 (View on PubMed)

Other Identifiers

4364

Identifier Type: -

Identifier Source: org_study_id