Red Blood Cells From Umbilical Cord for Transfusion of Preterm Infants

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Infant, Extremely Premature, Erythrocyte Transfusion, Umbilical Cord Issue

Intervention / Treatment
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* Other: Red blood cell from umbilical cord blood
* Other: Red blood cell from adult donor


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 12 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a pilot, open, non-randomized, single-center clinical study, whose main objective is to evaluate the safety, feasibility and efficacy of red blood cell from umbilical cord blood (UCB-RBC) transfusion in extremely preterm infants (EPI). When infants fit criteria for red blood cells transfusion the blood bank of reference will be contacted and availability of compatible UCB-RBC bags within those 6 hours will be checked. When it is possible (available compatible UCB-RBC bag within 6 hours), UCB-RBC will be transfused, otherwise patient will receive RBC from adult donor. Patients who initially received RBC from adult donor will remain in this group if repeated transfusions are needed. In patients who initially received UCB-RBC transfusion, availability of compatible UCB-RBC bags will have to be reviewed again. Only when it is not possible to transfuse UCB-RBC at this repeated occasion, the patient will receive RBC from adult blood donor.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients exclusively transfused with UCB-RBC<br>Interventional group infants arm will receive UCB-RBC bag when RBC transfusion is indicated as per standard practice, and when UCB-RBC is available within the first 6 hours of the request. | Other: Red blood cell from umbilical cord blood<br>* 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.<br>|
| Active Comparator: Patients exclusively transfused with AB-RBC<br>Standard treatment group infants arm will receive AB-RBC when RBC transfusion is indicated as per standard practice, and compatible UCB-RBC bag is not available. | Other: Red blood cell from adult donor<br>* 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.<br>|
| No Intervention: Non transfused patients<br>Patients with no indications for RBC transfusion. Their clinical management will be the usual in our neonatal unit. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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) | 
| 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) | 
| 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) | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anaemia of prematurity, Extremely preterm infants, Umbilical cord blood, Blood bank, Fetal hemoglobin