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Commentary
December 21, 2011

The Search for Effective Therapy for Sepsis: Back to the Drawing Board?

JAMA. 2011;306(23):2614-2615. doi:10.1001/jama.2011.1853

New therapeutic approaches for sepsis have not fared well recently. In January, Eisai announced that its worldwide phase 3 randomized trial of a novel anti–Toll-like receptor (TLR)-4 compound, eritoran tetrasodium, had failed to demonstrate an improvement in the primary end point of 28-day all-cause mortality in a cohort of 2000 patients with severe sepsis.1 This news was disappointing, especially because the manipulation of TLR4 signaling would represent a new avenue of research and drug development. Perhaps ironically, only a few months later, the importance of TLR4 signaling was recognized with the award of the Nobel Prize in Physiology or Medicine to Jules Hoffmann and Bruce Beutler for their work in this area.2

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