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.

Abstract

BACKGROUND AND OBJECTIVES Pathogen reduction technology using amustaline (S-303) was developed to reduce the risk of transfusion-transmitted infection and adverse effects of residual leucocytes. In this study, the viability of red blood cells (RBCs) prepared with a second-generation process and stored for 35 days was evaluated in two different blood centres. MATERIALS AND METHODS In a single-blind, randomized, controlled, two-period crossover study (n = 42 healthy subjects), amustaline-treated (Test) or Control RBCs were prepared in random sequence and stored for 35 days. On day 35, an aliquot of 51 Cr/99m Tc radiolabeled RBCs was transfused. In a subgroup of 26 evaluable subjects, 24-h RBC post-transfusion recovery, mean life span, median life span (T50 ) and life span area under the curve (AUC) were analysed. RESULTS The mean 24-h post-transfusion recovery of Test and Control RBCs was comparable (83.2 +/- 5.2 and 84.9 +/- 5.9%, respectively; P = 0.06) and consistent with the US Food and Drug Administration (FDA) criteria for acceptable RBC viability. There were differences in the T50 between Test and Control RBCs (33.5 and 39.7 days, respectively; P < 0.001), however, these were within published reference ranges of 28-35 days. The AUC (per cent surviving x days) for Test and Control RBCs was similar (22.6 and 23.1 per cent surviving cells x days, respectively; P > 0.05). Following infusion of Test RBCs, there were no clinically relevant abnormal laboratory values or adverse events. CONCLUSION RBCs prepared using amustaline pathogen reduction meet the FDA criteria for post-transfusion recovery and are metabolically and physiologically appropriate for transfusion following 35 days of storage.