Study to Assess S303 RBCs and Evaluate Safety and Efficacy in Patients Requiring Transfusion Support of Acute Anemia

Study Overview
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Brief Summary
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The clinical study will assess the in-vitro characteristics of red blood cells (RBCs) per the European Union (EU) criteria for leukocyte depleted RBCs in additive solution and evaluate the safety and efficacy of S-303 treated RBCs in a patient population requiring RBC transfusion support for acute anemia.

Official Title
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A Randomized Controlled Double-Blind Phase 3 Study to Assess Characteristics of S 303 Treated RBC Components and Evaluate Safety and Efficacy in Patients Requiring Transfusion Support of Acute Anemia

Conditions
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Focus:Use of S303 RBCs in Patients With Acute Anemia

Intervention / Treatment
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* Biological: S-303 Red Blood Cells (RBCs) - Test
* Biological: Conventional, untreated red blood cells (RBCs) - Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years, of either gender. Must be willing to use an acceptable form of contraceptive while on study (as approved by the Investigator or designee) Must be readily available by telephone Must provide an informed consent for study participation and have signed an ethics committee (EC)-approved informed consent Must have a negative cross match to S 303 red blood cells (RBCs) at study entry Must have a blood type of either A+ or O+ Patients must have a likelihood of receiving a transfusion as determined by the Investigator OR a Transfusion Risk Understanding Screening Tool (TRUST) Score of ≥3 at study entry Must be scheduled to receive one of the following operative procedures: Coronary artery bypass graft only, first procedure Valve repair or replacement only, first procedure A combination of first time Coronary Artery Bypass Graft (CABG) and valve repair or replacement After consultation with the Medical Monitor, provision can be made to enroll patients who may meet these general criteria but whose surgical procedure is not precisely described in the above categories. Such patients will be classified as other with their explicit condition reported with other study data. Exclusion Criteria: A positive pregnancy test result Inability of patient to comply with the protocol in the opinion of the Investigator or attending physician Breast-feeding of an infant or child Active autoimmune hemolytic anemia, or a positive Direct Antiglobulin Test (DAT) result Treatment with any medication that is known to adversely affect red blood cell viability Emergent or salvage surgical status at the time of surgery defined as follows: Presence of ongoing ischemia including angina at rest despite maximal medical therapy Acute evolving myocardial infarction within 24 hours before surgery Pulmonary edema requiring intubation Presence of shock or hemodynamic instability with or without circulatory support Systolic blood pressure < 80 mm Hg and/or Cardiac Index < 1.8 despite medical intervention (intravenous inotropes or similar pharmacologic agents) Cardiopulmonary resuscitation in the 24 hours prior to surgery or anesthesia induction Requiring an intra-aortic balloon pump or ventricular assist device Participation in any one of the following types of clinical studies either concurrently or within the previous 28 days: investigational blood products, pharmacologic agents or imaging materials, including dyes, investigational surgical techniques, or devices. Studies of nutrition, psychology, or socioeconomic issues are not grounds for exclusion Current diagnosis of either chronic or acute renal failure (requiring dialysis) or a serum creatinine greater than or equal to 1.8 mg/dL within 30 days prior to the start of surgery Current diagnosis of either chronic or acute hepatic insufficiency or a total serum bilirubin greater than or equal to 2.0 mg/dL within 30 days prior to the start of surgery Pre-existing RBC antibody that may make the provision of compatible study red blood cell (RBC) components difficult Patients requiring plasma removal or irradiation of the RBC Patients with prior history of severe allergic transfusion reactions A positive cross match to S 303 treated RBC -

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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S-303 Treated Red Blood Cells<br>Patients receive S-303 treated red blood cells (RBCs). | Biological: S-303 Red Blood Cells (RBCs) - Test<br> <br> |
| Active Comparator: Conventional, untreated Red Blood Cells<br>Patients receive conventional, untreated red blood cells (RBCs). | Biological: Conventional, untreated red blood cells (RBCs) - Control<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Endpoint - mean hemoglobin content | The mean hemoglobin content per red blood cell (RBC) component compared between the treatment groups | Day 2 | 
| Primary Safety Endpoint - Adverse events | The frequency of adverse events (related and unrelated to study RBC components) will be compared between the treatment groups. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Efficacy Endpoint | Proportion of RBC components that have adenosine-5'-triphosphate (ATP) levels of greater than 2 μmol/L | Day 35 | 
| Secondary Efficacy Endpoint | Proportion of RBC components that meet the European Union (EU) guideline for hemoglobin content, hematocrit, and hemolysis at the end of storage | Day 35 | 
| Secondary Efficacy Endpoint | Proportion of RBC components that have plasma-free hemoglobin levels corresponding to ≤ 0.8% hemolysis | Day 35 |