Rejuvesol® Washed RBC in Sickle Cell Patients Requiring Frequent Transfusions

Study Overview
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Brief Summary
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The objective of this proposal is to test the feasibility of red blood cell (RBC) rejuvenation to chronic transfusion in sickle cell disease (SCD) and the potential benefit of RBC rejuvenation in this population to determine if a larger clinical trial powered to definitively characterize the benefits of rejuvenation is warranted. This is a small pilot study is to see if restoring important energy molecules (ATP and 2,3,DPG) in stored red blood cells before they are transfused, with a rejuvenating solution (Rejuvesol), offers any advantages to individuals over standard blood transfusion. Subjects will receive either rejuvenated (R) or standard (S) RBCs with each transfusion for 6 transfusions (over approximately a 6-month period) in a pre-defined order to maximize detection of any signal.

Detailed Description
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Blood transfusion is part of the standard care for individuals that have sickle cell disease. Often these transfusions become needed quite frequently. The purpose of the red blood cells in the blood is to deliver oxygen to the organs and tissues of the body. People with sickle cell disease have abnormal red blood cells. Stored blood undergoes some changes that may make it less effective in achieving this goal. The purpose of this study is to see if restoring important energy molecules (ATP and 2,3,DPG) in stored red blood cells before they are transfused, with a rejuvenating solution (Rejuvesol), offers any advantages to individuals over standard blood transfusion. This is a Food and Drug Administration (FDA) approved process that is described by the American Association of Blood Banks for prolonging blood storage but not used for everyday transfusions. The investigators want to use this process to improve blood transfused to individuals who need frequent transfusions. Potential advantages include better delivery of oxygen by the transfused red blood cells and easier release of oxygen to the tissues. In addition the study will assess how using the rejuvenated blood affects the interval between transfusions. This means possibly that transfusions may not be needed as often. Although Rejuvesol has been previously approved by the FDA, it is not routinely used to prepare standard blood transfusions to individuals who have sickle cell disease. Use of Rejuvesol in this study is considered investigational.

Official Title
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Rejuvesol® Washed RBC in Sickle Cell Patients Requiring Frequent Transfusions

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Rejuvesol
* Procedure: Blood transfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable, compliant, chronically transfused sickle cell disease (SCD) patients Currently maintained crisis-free with repeated RBC therapy for at least 3 consecutive sessions ≥18 years old Have Hb SS disease Have the capacity to give informed consent Exclusion Criteria: Baseline need for washed RBCs Pre-treatment SaO2 < 92%.

Ages Eligible for Study
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Minimum Age: 18 Years

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: Other
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transfusion with rejuvenated red blood cells (RBCs)<br>Subjects with sickle cell disease will receive RBCs treated with Rejuvesol®. Scheduled red cell exchanges performed with the last 4 units of the exchange having been incubated with Rejuvesol® solution. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study. | Drug: Rejuvesol<br> <br> Procedure: Blood transfusion<br>* Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.<br>|
| Active Comparator: Transfusion with standard red blood cells<br>Subjects with sickle cell disease will receive standard RBCs. Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study. | Procedure: Blood transfusion<br>* Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Percent Hemoglobin (HbA) Decrement Per Day | The %HbA decrement is the current pre-treatment HbA - previous post treatment HbA in %. The average %HbA decrement per day was calculated using matched pairs. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actual HbA Decrement (g/dl) With Indexing to Calculated Circulating Blood Volume |  | 6 months | 
| Actual HbA Decrement (g/dl) Without Indexing to Calculated Circulating Blood Volume |  | 6 months | 
| Change in RBC Microparticles (MP) Counts |  | 6 months | 
| Change in RBC/RBC-MP-mediated Thrombin Generation |  | 6 months | 
| Change in p50 Pre- and Post-transfusion |  | 6 months |