PAEAN adds a second phase 3 no-benefit result for high-dose erythropoietin in cooled HIE

In 313 infants with moderate or severe HIE, death or moderate/severe developmental deficit occurred in 34.1% with erythropoietin and 28.7% with placebo (RR 1.19, 95% CI 0.84–1.68). Together with HEAL, PAEAN weakens the efficacy case while leaving rare-harm uncertainty.

The result is absence of demonstrated benefit—not proof of equivalence

EPO did not demonstrate any adjunctive effect to hypothermia, but no safety concerns were evident.

PAEAN was a phase 3, double-blind, placebo-controlled superiority trial across 24 NICUs in Australia, New Zealand, and Singapore. It randomized 313 infants receiving therapeutic hypothermia for moderate or severe hypoxic-ischemic encephalopathy: 156 to high-dose epoetin alfa and 157 to saline placebo. The primary question was patient-centered and appropriately hard—death or moderate/severe motor or cognitive deficit at 2 years.

The primary outcome occurred in 47/138 infants assigned erythropoietin (34.1%) and 41/143 assigned placebo (28.7%): unadjusted RR 1.19 (95% CI 0.84–1.68; P=.33). The observed absolute difference was 5.4 percentage points in the unfavorable direction. The interval crosses no effect and remains compatible with both some benefit and clinically meaningful harm; the defensible conclusion is that this regimen did not demonstrate benefit.

What PAEAN actually tested