Evaluation of the efficacy and safety of amustaline/glutathione pathogen-reduced RBCs in complex cardiac surgery: the Red Cell Pathogen Inactivation (ReCePI) study-protocol for a phase 3, randomized, controlled trial.

BACKGROUND: Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. METHODS: ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. DISCUSSION: RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.

Prevalence of hepatitis B infection among young and unsuspecting Hmong blood donors in the Central California Valley.

Chronic hepatitis B virus (HBV) infection may result in cirrhosis and/or hepatocellular carcinoma and is one of the leading causes of mortality in Asian Americans including Hmong Americans. The Central California Valley is home to a huge Hmong population. To date, the true prevalence of HBV among Hmong is largely unknown. The aim of this study was to contribute to the limited data on HBV prevalence and its trends in Hmong population in the Central California Valley. Between fiscal years 2006 and 2010, a total of 219, 450 voluntary donors were identified at Central California Blood Center in Fresno. Of these, 821 (399 males and 422 females) were Hmong donors. A cross-sectional review of the HBV (hepatitis B surface antigen) positivity among all donors was carried out. Prevalence estimates with 95% confidence intervals (CI) were calculated. Ninety-two percent of Hmong donors were between age groups 16 and 35 years, and only 8% were ≥36 years. The overall prevalence in Hmong was noted at 3.41% (95%CI 2.3-4.9) compared to 0.06% (95%CI 0.05-0.07) in donors of all ethnicities. The calculated prevalence could be an underestimate of the true HBV prevalence in Hmong as the study enrolled only healthy blood donors with predominant younger age (≤35 years) population. These results underscore the persistent burden of HBV infection and potentially increased risk of premature death even in the second generation Hmong community of the Central California Valley. This study reemphasizes the unequivocal need to develop robust preventive and treatment strategies for HBV in Hmong community.