Clinical trials for severe sepsis. Past failures, and future hopes.

Recent clinical trials with experimental immunotherapeutic agents for severe sepsis and septic shock have been largely unsuccessful despite seemingly convincing preclinical evidence of significant benefit of these antisepsis therapies. This article reviews basic therapeutic rationale, preclinical evaluation, and clinical trial design of past clinical trials of innovative sepsis treatments. Lessons learned from past failures should provide insights into the design and implementation of successful clinical trials for new anti-sepsis agents in the future.