Format

Send to

Choose Destination
Trends Mol Med. 2014 Apr;20(4):195-203. doi: 10.1016/j.molmed.2014.01.007. Epub 2014 Feb 24.

Why have clinical trials in sepsis failed?

Author information

1
The Departments of Surgery and Critical Care Medicine, and the Keenan Research Centre for Biomedical Science, St Michael's Hospital, 4th Floor Bond Wing, Room 4-007, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada; The Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: marshallj@smh.ca.

Abstract

The systemic inflammatory response is biologically complex, redundant, and activated by both infectious and noninfectious triggers. Its manipulation can cause both benefit and harm. More than 100 randomized clinical trials have tested the hypothesis that modulating the septic response to infection can improve survival. With one short-lived exception, none of these has resulted in new treatments. The current challenge for sepsis research lies in a failure of concept and reluctance to abandon a demonstrably ineffectual research model. Future success will necessitate large studies of clinical and biochemical epidemiology to understand the course of illness, better integration of basic and clinical science, and the creation of stratification systems to target treatment towards those who are most likely to benefit.

KEYWORDS:

adjuvant therapy; biologic response modifier; clinical trials; innate immunity; intensive care; sepsis; septic shock; staging

PMID:
24581450
DOI:
10.1016/j.molmed.2014.01.007
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center