Jackson, Bryon

Abstract Background Red blood cell (RBC) transfusion may be lifesaving, however transfusion-transmitted infections (TTI) and transfusion-associated graft-versus-host disease (TA-GVHD) still pose a threat despite current donor selection and testing requirements. Amustaline (S-303)/glutathione (GSH) pathogen reduction (PR) is designed to inactivate infectious microbes and leukocytes in RBCs. The RedeS study evaluates the safety and efficacy of amustaline/GSH PR-RBCs compared to conventional RBCs in a broad spectrum of patients requiring acute and/or repeated RBC transfusion support. Methods RedeS is a Phase 3, prospective, multi-center, randomized, double-blind, active-controlled, parallel-design study, with a 6-month extension option to evaluate patients requiring repeated transfusions including red cell exchange (RCE).Eligible subjects will be stratified according to site, baseline bleeding status and participation in the extension period. The study arms include a transfusion period of 28-days for anemia with any bleeding or non-bleeding patients or a 28-day+6-month extension for non-bleeding patients with chronic anemia requiring repeated simple transfusions, or for patients with sickle cell disease (SCD) expected to receive three RCE procedures. The study will seek to enroll 600-800 subjects in the overall safety analysis, including ~140 repeatedly-transfused subjects in the 6-month extension including up to 30 subjects receiving three RCE procedures. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days after the last study transfusion, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to PR-RBCs. The primary efficacy endpoint is the hemoglobin (Hb) increment in subjects who are non-bleeding at baseline, adjusted for the grams of Hb transfused and averaged over multiple transfusions. With 352 evaluable transfused non-bleeding subjects (176 per treatment group) from either arm, the study will have 80% power to demonstrate non-inferiority, defined as a Hb increment treatment difference of no more than 15% of the Control group mean, assuming a Control arm coefficient of variation of 50%. Discussion RedeS will characterize the safety of amustaline/GSH PR-RBCs and is designed to demonstrate the non-inferiority of PR-RBCs to conventional RBCs with respect to Hb increment, a common pragmatic clinical assessment of RBC transfusion effectiveness.

AbstractBackgroundAnemia is associated with poor outcome after major joint replacement surgery, but it is unclear whether sex and race modify its impact on outcome. We hypothesized that anemia would be associated with increased morbidity or mortality after knee arthroplasty surgery and that sex and race would be effect modifiers for this relationship.Study Design and MethodsWe performed a retrospective cohort study of elective knee arthroplasty patients between 2013 and 2018 using data from the National Surgical Quality Improvement Program. Morbidity or mortality after surgery was compared between patients without anemia, with mild anemia, and with moderate to severe anemia. Multivariable logistic regression was used to determine adjusted odds for morbidity or mortality with anemia. Interaction terms were entered into the model to test for effect modification by sex and race.Results243 491 patients were included and 30 135 patients (12.4%) were anemic. Morbidity or mortality occurred in 3.7% of patients without anemia, 5.2% of patients with mild anemia, and 7.1% of patients with moderate to severe anemia (P < .001). After adjustment for confounding variables, mild anemia OR = 1.36 (95% CI = 1.28‐1.45), and moderate to severe anemia OR = 1.92 (95% CI = 1.72‐2.13) were associated with increased odds of morbidity or mortality. Sex, but not race, was a significant effect modifier with men having a greater increase in morbidity or mortality when anemic (P = .02).ConclusionsAnemia is associated with increased morbidity or mortality after knee arthroplasty surgery and men have a greater increase in perioperative risk than women when anemic.