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

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
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)

Conditions
-----------------
Thalassemia Major

Intervention / Treatment
-----------------
* Biological: Blood component A
* Biological: Blood component B


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Patients will be divided into two groups of approximately equal number. The first group will receive the blood component A for a period of 6 months and then the blood component B for the next 6 months. The second group will receive the blood components in inverted order
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence A-B<br>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<br>* PRBCs obtained from whole blood after separation of plasma, buffy coat, and RBCs and successive leukoreduction of RBCs<br>Biological: Blood component B<br>* PRBCs obtained by leukoreduction of whole blood, and successive separation of plasma and RBCs<br>|
| Experimental: Sequence B-A<br>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<br>* PRBCs obtained from whole blood after separation of plasma, buffy coat, and RBCs and successive leukoreduction of RBCs<br>Biological: Blood component B<br>* PRBCs obtained by leukoreduction of whole blood, and successive separation of plasma and RBCs<br>|

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) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Packed RBCs, leukodepletion, buffy-coat, transfusion