Retinopathy of PrematurityPhase 2BORNNCT05100212
umBilical Or Adult Donor Red Blood Cells in Extremely Low Gestational Age Neonates and Retinopathy of Prematurity (BORN)
A Phase 2 study testing cord blood-RBC concentrates and adult donor RBC concentrates in people with Retinopathy of Prematurity, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 10 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 24 to 27 weeks
- Conditions the study is for
- Retinopathy of Prematurity
- What is being tested?
- cord blood-RBC concentrates and adult donor RBC concentrates
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 146 participants
- Where
- 10 sitesItaly
- Study dates
- 1 Dec 2021to 15 Jan 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 27 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- gestational age (GA) at birth between 24+0 and 27+6 weeks
- signed informed consent of parents.
Who cannot join
- 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.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Italy10 sites
Azienda Ospedaliero Universitaria Careggi
Florence
Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo,
Foggia
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan
AORN Santobono-Pausilipon
Naples
Ospedale Evangelico Villa Betania
Naples
Fondazione IRCCS Policlinico S. Matteo
Pavia
Azienda Ospedaliero Universitaria Pisana
Pisa
Azienda Ospedaliera Bianchi Melacrino Morelli
Reggio Calabria
Fondazione Policlinico Universitario A.Gemelli IRCCS
Rome, 00168
Città della Salute e della Scienza
Torino
About this study
Official title: Umbilical or Adult Donor Red Blood Cells to Transfuse Extremely Low Gestational Age Neonates. A Randomized Trial to Assess the Effect on Retinopathy of Prematurity Severity.
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
- Being tested
- cord blood-RBC concentrates, adult donor RBC concentrates
- Medical subject headings
- Retinopathy of Prematurity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cord blood-RBC concentratesBiological
Also called cord blood packed RBC
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).
adult donor RBC concentratesBiological
Also called adult donor packed RBC
Patients in the comparator arm are candidates to receive adult donor-RBC units
| Study group | Role | What they receive |
|---|---|---|
| Adult-RBC transfusions | Active comparator | Adult-red blood cell concentrate transfusions Receives: Biological: adult donor RBC concentrates |
| CB-RBC transfusions | Experimental | Cord blood-red blood cell concentrate transfusions Receives: Biological: cord blood-RBC concentrates |
What is being measured
The primary outcome is the main question the study is designed to answer.
Retinopathy of prematurity
Incidence of severe ROP (stage 3 and higher) in CB-RBC and A-RBC arms
Measured: up to the age of 40 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2021
- Study start1 Dec 2021
- Primary completion15 Jan 2025
- Study completion15 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Retinopathy of PrematurityStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Interventional, randomized, controlled, double-blind, with an adaptive design to evaluate safety and efficacy of allogeneic CB-RBC transfusions.
- Masking
- Single blind
- Who is masked
- Care provider
- Enrolment
- 146 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Fresenius Kabi
- Responsible party
- Sponsor
- Investigators
- Luciana Teofili, MD, Principal investigator, Fondazione Policlinico Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05100212
- Sponsor's protocol ID
- 4364
- Acronym
- BORN
- Status last verified
- Oct 2024
- First submitted
- 14 Oct 2021
- Last updated
- 27 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 39113069Teofili 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.
PubMed 36514106
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Umbilical or Adult Donor Red Blood Cells to Transfuse Extremely Low Gestational Age Neonates. A Randomized Trial to Assess the Effect on Retinopathy of Prematurity Severity.
- ClinicalTrials.gov ID
- NCT05100212
- Acronym / sponsor ID
- BORN / 4364
- Conditions
- Retinopathy of Prematurity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 146 participants (actual)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Collaborators
- Fresenius Kabi
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 15 Jan 2025 (actual)
- Study completion
- 15 Jan 2025 (actual)
- First posted
- 29 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (care provider)
- Number of arms
- 2
- Model description
- Interventional, randomized, controlled, double-blind, with an adaptive design to evaluate safety and efficacy of allogeneic CB-RBC transfusions.
| Arm | Type | Receives |
|---|---|---|
| Adult-RBC transfusions | Active comparator | Biological: adult donor RBC concentratesAdult-red blood cell concentrate transfusions |
| CB-RBC transfusions | Experimental | Biological: cord blood-RBC concentratesCord blood-red blood cell concentrate transfusions |
Who may qualify
- Ages
- 24 to 27 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- gestational age (GA) at birth between 24+0 and 27+6 weeks
- signed informed consent of parents.
Key exclusion criteria (8 listed)
- maternal-fetal immunization
- hydrops fetalis
- major congenital malformations associated or not with genetic syndromes
- previous transfusions
- hemorrhage at birth
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cord blood-RBC concentratesAlso: cord blood packed RBCPatients 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). | Biological | CB-RBC transfusions |
| adult donor RBC concentratesAlso: adult donor packed RBCPatients in the comparator arm are candidates to receive adult donor-RBC units | Biological | Adult-RBC transfusions |
Primary outcome
Retinopathy of prematurity
Time frame: up to the age of 40 weeks
Incidence of severe ROP (stage 3 and higher) in CB-RBC and A-RBC arms
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2025.
- Derived from this study: PubMed 39113069Teofili 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.
- Derived from this study: PubMed 36514106Teofili 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.
Related trials for Retinopathy of Prematurity
RecruitingObservational study
An Observational Study to Collect Data on How Aflibercept (Eylea) Given Using a Paediatric Dosing Device is Used in Preterm Babies With Retinopathy of Prematurity in the United Kingdom (UK)
Retinopathy of Prematurity, Preterm Infants
RecruitingObservational study
The Correlation Between Red Cell Transfusion and Complications of Prematurity
Retinopathy of Prematurity (ROP), Bronchopulmonary Dysplasia (BPD)
RecruitingObservational study
Imaging Retinal Vasculature in Infant Eyes
Retinopathy of Prematurity
RecruitingPhase 1
Safety, PK and PD of FLQ-101 in Premature Neonates
Retinopathy of Prematurity (ROP)
Recruiting
Analyzing Retinal Microanatomy in Retinopathy of Prematurity to Improve Care
Retinopathy of Prematurity (ROP)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luciana Teofili, MD principal investigator
Fondazione Policlinico Gemelli IRCCS
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cord blood-RBC concentrates and adult donor RBC concentrates in people with Retinopathy of Prematurity, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 10 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Retinopathy of prematurity (time frame: up to the age of 40 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05100212, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2025.