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Related Experiment Videos

Innovative therapies for sepsis.

S Krishnagopalan1, R P Dellinger

  • 1Section of Critical Care Medicine, Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612-3833, USA.

Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
|October 18, 2001
PubMed
Summary

Sepsis and septic shock remain leading causes of death. Despite research into novel therapies targeting inflammation and coagulation, most clinical trials have failed to improve survival rates, highlighting challenges in sepsis treatment.

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Area of Science:

  • Critical Care Medicine
  • Immunology
  • Pathophysiology

Background:

  • Sepsis and septic shock are significant contributors to patient morbidity and mortality.
  • Despite advances in supportive care, mortality rates for sepsis have remained largely unchanged over the past two decades.
  • Numerous innovative therapies targeting the inflammatory and coagulation cascades have been explored.

Purpose of the Study:

  • To review the challenges and recent advancements in sepsis treatment strategies.
  • To evaluate the efficacy of novel therapeutic approaches in clinical trials.
  • To discuss reasons for the failure of early sepsis clinical trials and highlight promising recent findings.

Main Methods:

  • Review of recent clinical trials in sepsis research.

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  • Analysis of therapeutic strategies targeting cytokine activation, inflammation, and coagulation.
  • Evaluation of outcomes from trials involving corticosteroids, anti-tumour necrosis factor agents, and drotrecogin alfa (rhAPC).

    • Main Results:

    • Most innovative therapies in sepsis research have failed to demonstrate improved survival in clinical trials.
    • Potential reasons for trial failures include discrepancies between animal models and human patients, patient heterogeneity, and the complexity of inflammatory pathways.
    • Recent trials on corticosteroids, anti-tumour necrosis factor, and drotrecogin alfa (rhAPC) have reported positive results, with drotrecogin alfa being peer-reviewed and published.

    Conclusions:

    • The development of effective sepsis therapies is hindered by the complexity of the disease and limitations in preclinical models.
    • Despite past failures, recent positive trial outcomes, particularly for drotrecogin alfa, offer renewed hope for improving sepsis patient survival.
    • Further research and carefully designed clinical trials are crucial to overcome the challenges in treating sepsis and septic shock.