Red blood cells treated with the amustaline (S‐303) pathogen reduction system: a transfusion study in cardiac surgery

Abstract

BACKGROUND Nucleic acid–targeted pathogen inactivation technology using amustaline (S‐303) and glutathione (GSH) was developed to reduce the risk of transfusion‐transmitted infectious disease and transfusion‐associated graft‐versus‐host disease with red blood cell (RBC) transfusion. STUDY DESIGN AND METHODS A randomized, double‐blind, controlled study was performed to assess the in vitro characteristics of amustaline‐treated RBCs (test) compared with conventional (control) RBCs and to evaluate safety and efficacy of transfusion during and after cardiac surgery. The primary device efficacy endpoint was the postproduction hemoglobin (Hb) content of RBCs. Exploratory clinical outcomes included renal and hepatic failure, the 6‐minute walk test (a surrogate for cardiopulmonary function), adverse events (AEs), and the immune response to amustaline‐treated RBCs. RESULTS A total of 774 RBC unis were produced. Mean treatment difference in Hb content was –2.27 g/unit (95% confidence interval, –2.61 to –1.92 g/unit), within the prespecified equivalence margins (±5 g/unit) to declare noninferiority. Amustaline‐treated RBCs met European guidelines for Hb content, hematocrit, and hemolysis. Fifty‐one (25 test and 26 control) patients received study RBCs. There were no significant differences in RBC usage or other clinical outcomes. Observed AEs were within the spectrum expected for patients of similar age undergoing cardiovascular surgery requiring RBCs transfusion. No patients exhibited an immune response specific to amustaline‐treated RBCs. CONCLUSION Amustaline‐treated RBCs demonstrated equivalence to control RBCs for Hb content, have appropriate characteristics for transfusion, and were well tolerated when transfused in support of acute anemia. Renal impairment was characterized as a potential efficacy endpoint for pivotal studies of RBC transfusion in cardiac surgery.

Amustaline‐glutathione pathogen‐reduced red blood cell concentrates for transfusion‐dependent thalassaemia

“…Pathogen reduction was performed in a functionally closed system of plastic containers within 24 h of collection using final concentrations of Amustaline (0·2 mmol/L) and Glutathione (20 mmol/L) as described. (Cancelas et al , ; Brixner et al , ) Process validation studies of Test RBCC at each production site were conducted prior to initiating clinical transfusions. Post‐production and quality control studies were performed on a subset of Test RBCC on day 35 of storage (Erickson et al , ).…”

The long and winding road to pathogen reduction of platelets, red blood cells and whole blood

“…The RBC were transfused after a mean storage interval of 18Á9 days. No antibodies to S-303 RBC were detected (Brixner et al, 2018). An in vitro study on Mirasol RBC and an RCT enrolling exclusively paediatric onco-haematology patients were performed by Trakhtman et al (2019).…”

“…The RBC were transfused after a mean storage interval of 18·9 days. No antibodies to S‐303 RBC were detected (Brixner et al , ).…”

Transfusion‐associated graft‐versus‐host disease reexamined: potential for improved prevention using a universally applied intervention

“…The second‐generation system has undergone extensive evaluation and will be submitted for a European Conformity mark. The system has met FDA criteria for recovery and survival in humans, and met study endpoints in a clinical trial in a surgical patient population in Germany . Despite these encouraging observations, concerns still exist regarding alloantibody formation due to possible RBC alterations caused by the treatment.…”

“…The system has met FDA criteria 93,94 for recovery and survival in humans, and met study endpoints in a clinical trial in a surgical patient population in Germany. 95 Despite these encouraging observations, concerns still exist regarding alloantibody formation due to possible RBC alterations caused by the treatment. Thus, a recently completed clinical trial using the second-generation S-303 system in 80 thalassemia patients in Turkey and Italy had, as a primary endpoint, the monitoring of RBC immunogenicity after multiple transfusions as per local practices.…”