Red Blood Cells From Umbilical Cord for Transfusion of Preterm Infants

Erythrocyte Transfusion Clinical Trial

Official title:

Safety, Feasibility and Efficacy of Red Blood Cells From Umbilical Cord Blood for Transfusion of Extremely Preterm Infants: Clinical Phase

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05612919
• Other study ID #: BST-TSCU-01
• Status: Recruiting
• Phase: N/A
• Start date: September 13, 2023
• Est. completion date: August 2025

Study information

• Verified date: September 2023
• Source: Hospital Clinic of Barcelona
• Contact: Miguel María Alsina Casanova, MD
• Phone: 0034 93 227 56 00
• Email: mmalsina[@]clinic.cat
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study has been designed to demonstrate that red blood cell from umbilical cord blood (UCB-RBC) is a safe and available product for extremely preterm infants (EPI) transfusion and that transfusion of UCB-RBC is non-less effective than RBC from adult donor for the treatment of anemia of prematurity in this group of patients.

Description:

Prematurity is an important maternal and child health problem due to its incidence and associated complications. Anaemia is a frequent problem in extremely preterm infants (EPI) whose treatment often requires red blood cell (RBC) transfusion. This product is currently obtained from adult blood (AB) donor. The incidence of some prematurity complications have been demonstrated to increase with AB-RBC tranfusions mainly because of the higher oxygen tissue release, such as retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC). In addition, AB-RBC could contain small amounts of heavy metals that could be toxic for EPI.

RBC from umbilical cord blood (UCB-RBC) might be a better alternative as it does not change the hemoglobin profile and consequently might decrease the oxygen toxicity.

Several studies have evaluated the safety of UCB-RBC transfusions in preterm infants without finding a higher risk of complications compared with AB-RBC transfusions.

A pilot study has been designed to evaluate the safety of UCB-RBC for transfusion in EPI and to determine the feasibility and efficacy of UCB-RBC for transfusion in this group of patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 12 Weeks

Eligibility

Inclusion Criteria:

• Signed informed consent from parents or legal guardians

• Preterm infants born earlier than 28 weeks of gestational age.

• Admission to the neonatal intensive care unit of the participating hospital (Hospital Clínic of Barcelona)

Exclusion Criteria:

• Previous transfusion

• Isoimmunization

• Hydrops fetalis

• Major congenital malformations

• Congenital infections

• Hemoglobinopathies

• Extreme urgency of blood availability (hypovolemic shock, disseminated intravascular coagulopathy...)

• Be part of another clinical trial that may interfere with the results

Related Conditions & MeSH terms

• Erythrocyte Transfusion
• Infant, Extremely Premature
• Premature Birth
• Umbilical Cord Issue

Intervention

Other:
• Red blood cell from umbilical cord blood
Patients will receive a volume of 15-20 ml/kg of red blood cell from umbilical cord blood (UCB-RBC). The transfusion will be prescribed and administered with all the routine safety measures carried out by the nurses to ensure compatibility between the administered RBC and the patient. The UCB-RBC bags will contain a minimum volume of 20 mL of RBC, with a haematocrit of about 60% and an acceptable residual leucocyte content of <106/mm3. Product validation is currently under development.
• Red blood cell from adult donor
Patients will receive a volume of 15-20 ml/kg of red blood cell from adult donor according to standard guidelines. The transfusion will be prescribed and administered with all the routine safety measures carried out by the nurses to ensure compatibility between the administered RBC and the patient. Blood samples are irradiated according to standard practise.

Locations

Country	Name	City	State
Spain	Hospital Clinic of Barcelona	Barcelona

Sponsors (3)

Lead Sponsor	Collaborator
Hospital Clinic of Barcelona	Banc de Sang i Teixits, Institut d'Investigacions Biomèdiques August Pi i Sunyer

Country where clinical trial is conducted

Spain, 

References & Publications (10)

Bianchi M, Giannantonio C, Spartano S, Fioretti M, Landini A, Molisso A, Tesfagabir GM, Tornesello A, Barbagallo O, Valentini CG, Vento G, Zini G, Romagnoli C, Papacci P, Teofili L. Allogeneic umbilical cord blood red cell concentrates: an innovative blood product for transfusion therapy of preterm infants. Neonatology. 2015;107(2):81-6. doi: 10.1159/000368296. Epub 2014 Nov 15. — View Citation

Bianchi M, Orlando N, Barbagallo O, Sparnacci S, Valentini CG, Carducci B, Teofili L. Allogeneic cord blood red blood cells: assessing cord blood unit fractionation and validation. Blood Transfus. 2021 Sep;19(5):435-444. doi: 10.2450/2020.0138-20. Epub 2020 Nov 3. — View Citation

Gonzalez EG, Casanova MA, Samarkanova D, Aldecoa-Bilbao V, Teresa-Palacio M, Busquets EF, Figueras-Aloy J, Salvia-Roiges M, Querol S. Feasibility of umbilical cord blood as a source of red blood cell transfusion in preterm infants. Blood Transfus. 2021 Nov;19(6):510-517. doi: 10.2450/2020.0169-20. Epub 2020 Dec 18. — View Citation

Hellstrom W, Martinsson T, Hellstrom A, Morsing E, Ley D. Fetal haemoglobin and bronchopulmonary dysplasia in neonates: an observational study. Arch Dis Child Fetal Neonatal Ed. 2021 Jan;106(1):88-92. doi: 10.1136/archdischild-2020-319181. Epub 2020 Aug 26. — View Citation

Jiramongkolchai K, Repka MX, Tian J, Aucott SW, Shepard J, Collins M, Kraus C, Clemens J, Feller M, Burd I, Roizenblatt M, Goldberg MF, Arevalo JF, Gehlbach P, Handa JT. Lower foetal haemoglobin levels at 31- and 34-weeks post menstrual age is associated with the development of retinopathy of prematurity : PacIFiHER Report No. 1 PacIFiHER Study Group (Preterm Infants and Fetal Haemoglobin in ROP). Eye (Lond). 2021 Feb;35(2):659-664. doi: 10.1038/s41433-020-0938-5. Epub 2020 May 14. — View Citation

Kotowski M, Litwinska Z, Klos P, Pius-Sadowska E, Zagrodnik-Ulan E, Ustianowski P, Rudnicki J, Machalinski B. Autologous cord blood transfusion in preterm infants - could its humoral effect be the kez to control prematurity-related complications? A preliminary study. J Physiol Pharmacol. 2017 Dec;68(6):921-927. — View Citation

Mohamed A, Shah PS. Transfusion associated necrotizing enterocolitis: a meta-analysis of observational data. Pediatrics. 2012 Mar;129(3):529-40. doi: 10.1542/peds.2011-2872. Epub 2012 Feb 20. — View Citation

Strauss RG, Widness JA. Is there a role for autologous/placental red blood cell transfusions in the anemia of prematurity? Transfus Med Rev. 2010 Apr;24(2):125-9. doi: 10.1016/j.tmrv.2009.11.003. — View Citation

Teofili L, Papacci P, Orlando N, Bianchi M, Molisso A, Purcaro V, Valentini CG, Giannantonio C, Serrao F, Chiusolo P, Nicolotti N, Pellegrino C, Carducci B, Vento G, De Stefano V. Allogeneic cord blood transfusions prevent fetal haemoglobin depletion in preterm neonates. Results of the CB-TrIP study. Br J Haematol. 2020 Oct;191(2):263-268. doi: 10.1111/bjh.16851. Epub 2020 Jun 8. — View Citation

Widness JA. Pathophysiology of Anemia During the Neonatal Period, Including Anemia of Prematurity. Neoreviews. 2008 Nov 1;9(11):e520. doi: 10.1542/neo.9-11-e520. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Marrow regeneration	Comparison of reticulocyte counts between transfused and non-transfused patients.	1 month
Other	Ferritin value in transfused and non-transfused patients	Ferritin value will be assessed to comparison iron metabolism in transfused and non-transfused patients	1 month
Other	Transferrin saturation index (%) in transfused and non-transfused patients	Transferrin saturation index (%) will be assessed to comparison iron metabolism in transfused and non-transfused patients	1 month
Primary	Number of participants with abnormal physical examination after red blood cells from umbilical cord blood (UCB-RBC) transfusion	The number of participants with abnormal physical examination after UCB-RBC transfusion will be analyzed to evaluated the safety of UCB-RBC in extremely preterm infants (EPI)	24 hours after the procedure
Primary	Number of participants with abnormal vital signs after UCB-RBC transfusion	The number of participants with abnormal physical examination after UCB-RBC transfusion will be analyzed to evaluated the safety of UCB-RBC in EPI	24 hours after the procedure
Primary	Number of participants with altered value of continous monitoring of regional cerebral and somatic oxygen saturation by near-infrared spectroscopy after UCB-RBC transfusion	The number of participants with Altered value of continous monitoring of regional cerebral and somatic oxygen saturation by near-infrared spectroscopy after UCB-RBC transfusion will be analyzed to evaluated the safety of UCB-RBC in EPI	24 hours after the procedure
Primary	Number of participants with abnormalities in the result of acid-base balance and ionogram after UCB-RBC transfusion	The number of participants with abnormalities in the result of acid-base balance and ionogram after UCB-RBC transfusion will be analyzed to evaluated the safety of UCB-RBC in EPI	24 hours after the procedure
Primary	Number of participants with morbidities up to 36 weeks of postmenstrual age after UCB-RBC transfusion	The number of participants with Morbidities up to 36 weeks of postmenstrual age after UCB-RBC transfusion will be analyzed to evaluated the safety of UCB-RBC in EPI	24 hours after the procedure
Secondary	Feasibility of UCB-RBC in EPI	Feasibility will be considered proven if UCB-RBC is available in >50% of patients	within 6 hours of the request
Secondary	Total volumen of RBC transfused in transfused patients	Total volumen of RBC transfused measured in milliliters will be evaluated to assess the efficacy of UCB-RBC in EPI according to the treatment group (only UCB-RBC, only AB-RBC, both)	An average of 3 month (when patients are 36 weeks of postmenstrual age)
Secondary	Number of RBC tranfusions in transfused patients	The total number of RBC transfusions will be evaluated to assess the efficacy of UCB-RBC in EPI according to the treatment group (only UCB-RBC, only AB-RBC, both)	An average of 3 month (when patients are 36 weeks of postmenstrual age)
Secondary	The number of days between two consecutive RBC transfusion in transfused patients	The number of days between two consecutive RBC transfusion in each transfused patient will be evaluated to assess the efficacy of UCB-RBC in EPI according to the treatment group (only UCB-RBC, only AB-RBC, both)	An average of 3 month (when patients are 36 weeks of postmenstrual age)
Secondary	Total hemoglobin value (g/dl) in transfused patients	Total hemoglobin (g/dl) in transfused patients will be evaluated to assess the efficacy of UCB-RBC in EPI according to the type of transfusion (UCB-RBC vs AB-RBC) An increment in total hemoglobin by 4 ± 2 g / dL 24 hours after the transfusion will be considered significative. Samples will be analysed by microhematocrit method ("Rapidpoint 5000 system, Siemens").	Before transfusion, 24 hours, 1 week, 1 month after transfusion
Secondary	Hematocrit value (%) in transfused patients	Hematocrit (%) in transfused patients will be evaluated to assess the efficacy of UCB-RBC in EPI according to the type of transfusion (UCB-RBC vs AB-RBC) An increment in hematocrit by 12 ± 5 points 24 hours after the transfusion will be considered significative. Samples will be analysed by microhematocrit method ("Rapidpoint 5000 system, Siemens").	Before transfusion, 24 hours, 1 week, 1 month after transfusion
Secondary	Fetal haemoglobin value (%) in transfused patients	Fetal haemoglobin (%) in transfused patients will be evaluated to assess the efficacy of UCB-RBC in EPI according to the type of transfusion (UCB-RBC vs AB-RBC) A variation of fetal haemoglobin percentage between values before and after the transfusion will be considered significative. It will be analysed by capillary electrophoresis ("Capillary neonatal Hb" kit).	Before transfusion, 24 hours, 1 week, 1 month after transfusion
Secondary	Regional cerebral and somatic oxygen saturation (%) value	Regional cerebral and somatic oxygen saturation (%) in transfused patients will be evaluated to assess the efficacy of UCB-RBC in EPI according to the type of transfusion (UCB-RBC vs AB-RBC). Measurements will be taken by near-infrared spectroscopy	Before transfusion, 24 hours, 1 week, 1 month after transfusion