(P-TS-24) Design of ReCePI, a Randomized, Double-Blinded, Phase III Study to Evaluate the Efficacy and Safety of Pathogen Reduced RBCs in Complex Cardiac Surgery

Background/Case Studies: Pathogen reduction of RBCs (PR-RBCs) treated with amustaline/glutathione is an investigational process designed to reduce transfusion-transmitted infection and TA-GVHD. The Red Cell Pathogen Inactivation (ReCePI) study aims to evaluate the efficacy and safety of PR-RBC transfusions for support of acute anemia. An acute kidney injury (AKI) endpoint in cardiovascular surgery (CVS) was selected based on the hypothesis that RBC transfusions protect against tissue hypoxia and reduce the incidence of AKI, an outcome directly-related to 30-day mortality in CVS surgery (Lassnigg et al. J Am Soc Nephrol 2004; Crit Care Med 2008).

Study

Design/Methods: ReCePI is a prospective, multicenter, randomized, double-blinded, controlled, parallel, non-inferiority study (ClinicalTrials.gov: NCT03459287). The study population includes subjects ≥ 11 years of age undergoing complex CVS with a high (≥3) TRUST score risk of transfusion. Test components are leukocyte reduced RBCs treated with amustaline and glutathione suspended in SAG-M (PR- RBCs). Control components are leukoreduced RBC components in an FDA approved additive solution. Both are stored at 1-6°C for up to 35 days. Subjects with confirmed positive baseline antibody to PR-RBCs are excluded. Primary efficacy outcome is the proportion of patients who have received at least one study transfusion with renal impairment (AKI) defined as any increased serum creatinine (sCr) (≥0.3 mg/dL or 26.5 µmol/L) from the pre-surgery baseline sCr, within 48±4 hours of the end of surgery. Safety outcomes are the proportion of patients with any treatment-emergent adverse events related to study RBC transfusion through 28 days; and the proportion of patients with treatment-emergent antibodies with confirmed specificity to PR-RBCs. Assuming an AKI event rate of 30% in the Control group with no more than a 50% increase from the Control rate as the non-inferiority margin, a sample size of >292 patients (146 per arm) will provide approximately 80% power to declare non-inferiority at the two-sided 0.05 alpha level, assuming the true treatment difference is zero.

Results/Findings: ReCePI opened for enrollment at 18 US sites and transfused the first subject in December 2019. Enrollment was impacted by the COVID-19 pandemic. DSMB review on three occasions has recommended continued enrollment. In view of robust patient blood management practices and despite stringent selection criteria, only 56% of enrolled subjects are transfused (site range: 18-82%). To date, no cases of increased RBC clearance or hemolysis associated with antibodies to PR-RBCs have been documented. Average AKI rates for all patients are 30% but vary by site. The study remains blinded. Enrollment is expected to be completed in 2023.

Conclusions: The ReCePI study utilizes changes in the incidence of AKI as a robust assessment of PR-RBC safety and efficacy in severely ill CVS subjects with surgical blood loss.

Importance of research: The abstract describes the design of a Phase III study of pathogen reduced RBCs based on the novel endpoint of acute kidney injury in CVS patients.