Transfusion of Amustaline/Glutathione Pathogen-reduced Red Blood Cells in Cardiac Surgery: A Randomized Phase 3 Clinical Trial.

Summary

Among 581 randomized patients (321 transfused), AKI within 48 h occurred in 29.3% (pathogen-reduced) vs 28.0% (conventional), meeting noninferiority (difference 0.7%; 95% CI −8.9 to 10.4%; P=0.001 for noninferiority). KDIGO 7-day AKI rates were similar; stage III trended higher in pathogen-reduced (9.4% vs 4.3%; P=0.075). Low-titer, specific antibodies occurred in 3.1% without hemolysis.

Key Findings

• AKI within 48 h: 29.3% (pathogen-reduced) vs 28.0% (conventional); noninferiority met (difference 0.7%; 95% CI −8.9 to 10.4%; P=0.001).
• KDIGO 7-day AKI similar (37.1% vs 34.0%; P=0.53); stage III tended higher with pathogen-reduced (9.4% vs 4.3%; P=0.075).
• Low-titer, specific red cell antibodies occurred in 3.1% of pathogen-reduced recipients without hemolysis; hemoglobin nadirs were comparable.

Clinical Implications

Centers with access to amustaline/glutathione pathogen-reduced red cells may consider their perioperative use without increased AKI risk, with vigilance for rare low-titer alloantibodies and evaluation of broader safety (e.g., infection, TA-GVHD) and cost-effectiveness.

Limitations

• Only 55% of randomized patients were transfused with study RBCs; analyses focus on transfused population.
• Primary endpoint (AKI) is a surrogate; trend toward more stage III AKI warrants further study; long-term alloimmunization and infectious risk reduction not directly assessed.

Future Directions

Pragmatic trials assessing infection transmission, TA-GVHD, longer-term renal and immunologic outcomes, and cost-effectiveness across varied surgical populations.