The erythropoietin neuroprotective effect: assessment in CABG surgery (TENPEAKS): a randomized, double-blind, placebo controlled, proof-of-concept clinical trial.

BACKGROUND AND PURPOSE Neurocognitive dysfunction complicates coronary artery bypass surgery. Erythropoietin may be neuroprotective. We sought to determine whether human recombinant erythropoietin would reduce the incidence of neurocognitive dysfunction after surgery. METHODS We randomly assigned 32 elective first-time coronary artery bypass graft patients to receive placebo or 375 U/kg, 750 U/kg, or 1500 U/kg of recombinant human erythropoietin divided in 3 daily doses, starting the day before surgery. Primary outcomes were feasibility and safety, and secondary outcomes were neurocognitive dysfunction at discharge and 2 months. RESULTS All subjects were male, mean age 60 years (range 46 to 73). No significant differences were found in pump time, cross-clamp time, or hospital length of stay. Mortality and pure red cell aplasia were not observed. One patient in the 375 U/kg group had ST changes compatible with myocardial injury immediately postoperative, but no other thrombotic complications were observed. Neurocognitive dysfunction occurred in 21/32 (66%) of patients at discharge and 5/32 (16%) at 2 months. Neurocognitive dysfunction at discharge by group was: placebo 6/8 (75%), 375 U/kg 4/8 (50%), 750 U/kg 6/8 (75%), and 1500 U/kg 5/8 (63%). Neurocognitive dysfunction at 2 months by group was: placebo 3/8 (38%), 375 U/kg 1/8 (13%), 750 U/kg 1/8 (13%), and 1500 U/kg 0/8 (0%). Neurocognitive dysfunction at 2 months for erythropoietin at any dose was 2/24 (8.3%) versus 3/8 (38%) for placebo (P=0.085). CONCLUSIONS This study demonstrates feasibility and safety for the use of human recombinant erythropoietin as a neuroprotectant in coronary artery bypass graft surgery. A trend in the reduction of neurocognitive dysfunction at 2 months was associated with erythropoietin use. A multicenter randomized controlled trial is warranted.