PL1-SN-27 - Acute Kidney Injury to Evaluate Amustaline/Glutathione Pathogen Reduced Red Cells in Cardiac Surgery: Outcomes of the ReCePI Phase III Clinical Trial

The Red Cell Pathogen Inactivation (ReCePI) study utilized acute kidney injury (AKI) as an indicator of tissue oxygenation to evaluate amustaline/glutathione pathogen-reduced (PR) RBCs.

Study

Design/Methods: A Phase III, double-blinded, non-inferiority study randomized cardiac or thoracic aorta surgery patients at a high risk of RBC transfusion to receive PR (Test) or conventional (Control) RBCs during and for 7 days post-surgery. The primary endpoint was AKI within 48 hours of surgery. The study had 80% power to prove non-inferiority assuming 30% AKI incidence with conventional RBCs and a non-inferiority margin of half the conventional rate. Adverse events and treatment-emergent RBC antibodies were assessed through 28 and 75 days, respectively. A clinical stop was required if one subject had increased RBC clearance or hemolysis associated with a PR RBC-specific antibody.

Results/Findings: 581 subjects were randomized and 321 (55%) transfused with study RBCs, comprising the modified intention-to-treat (mITT) population. AKI within 48 hours of surgery correlated with death or the need for renal replacement therapy by day 30 post-surgery (OR 7.2, 95% C.I.  2.9, 18.1). The PR arm received fewer total RBCs within 48 hours of surgery (median 2.0 [range 1-16] Test; 3.0 [range 1-21] Control, P=0.048), had comparable total surgical blood loss (median 420 mL [range 10-3,135 mL] Test; 415 mL [range 20-4,045 mL] Control) and maintained similar hemoglobin levels (Figure). Forty six of 157 (29.3%) evaluable Test subjects versus 45 of 161 Control subjects (28.0%) met the AKI endpoint (treatment difference 0.74%, 95%C.I. -8.9%, 10.4%, non-inferiority margin 14.0%, P= 0.001 for non-inferiority). Non-study RBCs were transfused in 17.6% Test and 22.8% Control mITT subjects within 48 hours of surgery. In subjects receiving only study RBCs, 31 of 129 (24.0%) Test and 33 of 123 (26.8%) Control met the AKI endpoint (treatment difference -2.62%, 95%C.I. -13.0%, 7.8%, non-inferiority margin 13.4%, P=0.032 for non-inferiority). Adverse events and transfusion reactions were comparable between populations. Four Test and 4 Control subjects developed regular RBC alloantibodies. Five of 159 (3.1%) Test subjects developed low-titer antibodies with specificity for PR RBCs without clinical hemolysis. The DSMB reviewed each case and allowed the study to continue enrollment.

Conclusions:

PR RBCs met the predefined non-inferiority criteria for AKI compared with conventional RBCs, with a similar adverse event profile. Treatment-emergent antibodies with specificity for PR RBCs were uncommon and not clinically significant. (Funded by the Biomedical Advanced Research Development Authority (BARDA), DHHS; ClinicalTrials.gov, NCT03459287).