Impact of the Preparation Method of Red Cell Concentrates on Transfusion Indices in Thalassemic Patients

Prospective Crossover Study on Beta(ß)-Thalassaemia Transfusion-dependent to Evaluate the Impact on Transfusion Regimen of Two Pre-storage Leukoreduced PRBCs(In-line Filtration + B-C Separation; Whole Blood Filtration + B-C Conservation)

This study compares the effects of Packed Red Blood Cells (PRBCs) prepared in two different ways on the transfusion indices in beta(ß)-Thalassemia transfusion-dependent patients. The two blood components types derive from the whole blood. In one case, the whole blood is leukoreduced with subsequent plasma removal. In the other case, plasma, buffy coat, and red blood cells (RBCs) are first separated and subsequently, the RBCs leukoreduced. Each type of blood components will be subsequently given to one-half of the patients for a 6-month period and to the other half for other 6-month at the randomization phase, for a total of 12 months of crossed-treatment per patient.

Study Overview

• Status: Completed
• Conditions: Thalassemia Major
• Intervention / Treatment: Biological: Blood component A; Biological: Blood component B

Detailed Description

At Day Hospital Talassemia ed Emoglobinopatie of Ferrara, two different PRBCs are available. The two types of blood components are obtained from whole blood, pre-storage leukoreduced and suspended in saline-adenine-glucose-mannitol (SAGM). One method of preparation consists of the whole blood leukoreduction with subsequent plasma removal. The other method first separates plasma, buffy coat, and RBCs, and then the RBCs are leukoreduced. The two methods mainly differ in the final haemoglobin (Hb) content: the Hb level is lower (-13%, approximately) in the second method that also shows the advantage to produce platelets from the buffy coat. A PRBCs unit is not as strictly defined as a therapeutic medication dose (pill or vial): individual PRBCs units may substantially differ in their Hb content, much more than the average difference between the two types of preparations. The aim of this study is to document the extent of the average difference between the two types of preparations, and its impacts on the transfusion indices of ß-Thalassaemia transfusion-dependent patients. All patients will receive each blood component for a period of 6 months (crossover design), for a total of 12 months of transfusion treatment per patient.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Ferrara, Italy, 44134
    • Day Hospital Thalassaemia and Haemoglobinopathies (DHTE)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient with beta(ß)-Thalassaemia transfusion-dependent (ß-Thalassemia Major or ß-Thalassemia Intermedia transfusion-dependent, regularly transfused since at least 5 years

Exclusion Criteria:

• Patient not exclusively transfused at Day Hospital Thalassaemia and Haemoglobinopathies of Ferrara
• Patient with haemolytic auto-antibodies
• Patient transfused with washed Packet RBCs units
• Severe splenomegaly (>18 cm on echography)
• Elevated blood consumption (>200 mL/kg of pure RBCs in the last year)
• Patient receiving haemoglobin inducers in the last 6 months
• Any significant clinical pulmonary, cardiovascular, endocrine, hepatic, gastrointestinal, renal, infectious, immunological including significant allo- or auto-immunisation disease, considered not adequately controlled prior to the study
• Patient treated with erythrocyte exchange
• Pregnant females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sequence A-B; Patients in this arm will receive blood component A for 6 months and blood component B for the next 6 months	Biological: Blood component A; PRBCs obtained from whole blood after separation of plasma, buffy coat, and RBCs and successive leukoreduction of RBCs; Biological: Blood component B; PRBCs obtained by leukoreduction of whole blood, and successive separation of plasma and RBCs
EXPERIMENTAL: Sequence B-A; Patients in this arm will receive blood component B for 6 months and blood component A for the next 6 months	Biological: Blood component A; PRBCs obtained from whole blood after separation of plasma, buffy coat, and RBCs and successive leukoreduction of RBCs; Biological: Blood component B; PRBCs obtained by leukoreduction of whole blood, and successive separation of plasma and RBCs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transfusion Power Index	(Average pre-transfusion Hb concentration)/(Unit Index) [for the definition of Unit Index, see the secondary outcomes]	For each of the two blood components studied, at the end of 6-month period of study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average pre-transfusion Hb concentration	Mean pre-transfusion Hb levels, calculated starting from the second transfusion of the period to the first transfusion of the following period	For each of the two blood components studied, at the end of 6-month period of study
Unit Index	(Total number of PRBCs (A or B) transfused in the period)/(Number of days between the first transfusion of the period and the first transfusion of the following period)	For each of the two blood components studied, at the end of 6-month period of study
Average Transfusion Interval	(Number of days between the first transfusion of the period and the first transfusion of the following period)/(Number of transfusions in the period)	For each of the two blood components studied, at the end of 6-month period of study
Number of Transfusion Reactions	Number of transfusion reactions to the two blood components that may occur in the study periods (2 periods of 6 months each)	Study periods (2 periods of 6 months each)
Transfusion Reaction Rate	(Number of transfusion reactions to the two blood components occurring in the study periods)/(Total number of PRBCs (A or B) transfused in the period)	Study periods (2 periods of 6 months each)

Collaborators and Investigators

• Sponsor: Università degli Studi di Ferrara
• Investigators: Study Chair: Maria Rita Gamberini, MD, D.H. Thalassaemia-Haemoglobinopathies (DHTE) - A.O.U. S. Anna of Ferrara

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 14, 2018
• Primary Completion (ACTUAL): July 31, 2019
• Study Completion (ACTUAL): July 31, 2019

Study Registration Dates

• First Submitted: November 15, 2018
• First Submitted That Met QC Criteria: June 18, 2019
• First Posted (ACTUAL): June 19, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 12, 2021
• Last Update Submitted That Met QC Criteria: November 11, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: transfusion; Packed RBCs; leukodepletion; buffy-coat
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: CrossoverFE2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: There is a plan to make IPD (deidentified) available to other researchers and support already published results
• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication
• IPD Sharing Access Criteria: Please contact the Central Contact Person
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No