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.

Progress Toward Strengthening National Blood Transfusion Services - 14 Countries, 2011-2014.

Blood transfusion is a life-saving medical intervention; however, challenges to the recruitment of voluntary, unpaid or otherwise nonremunerated whole blood donors and insufficient funding of national blood services and programs have created obstacles to collecting adequate supplies of safe blood in developing countries (1). Since 2004, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) has provided approximately $437 million in bilateral financial support to strengthen national blood transfusion services in 14 countries in sub-Saharan Africa and the Caribbean* that have high prevalence rates of human immunodeficiency virus (HIV) infections. CDC analyzed routinely collected surveillance data on annual blood collections and HIV prevalence among donated blood units for 2011-2014. This report updates previous CDC reports (2,3) on progress made by these 14 PEPFAR-supported countries in blood safety, summarizes challenges facing countries as they strive to meet World Health Organization (WHO) targets, and documents progress toward achieving the WHO target of 100% voluntary, nonremunerated blood donors by 2020 (4). During 2011-2014, overall blood collections among the 14 countries increased by 19%; countries with 100% voluntary, nonremunerated blood donations remained stable at eight, and, despite high national HIV prevalence rates, 12 of 14 countries reported an overall decrease in donated blood units that tested positive for HIV. Achieving safe and adequate national blood supplies remains a public health priority for WHO and countries worldwide. Continued success in improving blood safety and achieving WHO targets for blood quality and adequacy will depend on national government commitments to national blood transfusion services or blood programs through increased public financing and diversified funding mechanisms for transfusion-related activities.

Blood component use in a sub-Saharan African country: results of a 4-year evaluation of diagnoses associated with transfusion orders in Namibia.

National blood use patterns in sub-Saharan Africa are poorly described. Although malaria and maternal hemorrhage remain important drivers of blood demand across Africa, economic growth and changes in malaria, HIV/AIDS, and noncommunicable disease epidemiology may contribute to changes in blood demand. We evaluated indications for blood use in Namibia, a country in southern Africa, using a nationally representative sample and discuss implications for the region. Clinical and demographic data related to the issuance of blood component units in Namibia were reviewed for a 4-year period (August 1, 2007-July 31, 2011). Variables included blood component type, recipient age and sex, and diagnosis. Diagnoses reported by clinicians were reclassified into International Statistical Classification of Diseases, 10th Revision categories. Multiple imputation methods were used to complete a data set missing age, sex or diagnosis data. Descriptive analyses were conducted to describe indications for transfusions and use of red blood cells (RBCs), platelets, and plasma. A total of 39,313 records accounting for 91,207 blood component units were analyzed. The median age of Namibian transfusion recipients was 45 years (SD, ±19). A total of 78,660 RBC units were issued in Namibia during the study period. Red blood cells transfused for "unspecified anemia" accounted for the single largest category of blood issued (24,798 units). Of the overall total, 38.9% were for diseases of the blood and blood-forming organs (D50-D89). Infectious disease (A00-B99), pregnancy (O00-O99), and gastrointestinal (K20-K93) accounted for 14.8%, 11.1%, and 6.1% of RBC units issued, respectively. Although a specific diagnosis of malaria accounted for only 2.7% of pediatric transfusions, an unknown number of additional transfusions for malaria may have been categorized by requesting physicians as unspecified anemia and counted under diseases of blood forming organs. During the study period, 9751 units of fresh-frozen plasma were issued. Nearly one-quarter of these units (23.1%) were issued for gastrointestinal (K20-K93) diagnoses. Malignant neoplasms (C00-C97) accounted for 38.1% of 2978 platelet units issued. Blood use in Namibia reflects changes in the health care system due to economic development, improvement in HIV/AIDS and malaria epidemiology, high rates of health care facility-based childbirth, and access to noncommunicable disease treatment. However, better documentation of the indications for transfusion is needed to confirm these observations. Changing patterns of health care will result in changing demands for blood components. Improved methods to evaluate blood use patterns in sub-Saharan Africa may help set realistic national blood collection goals.