Dexmedetomidine for Sepsis in ICU Randomized Evaluation Trial
Status:
Completed
Trial end date:
2016-01-01
Target enrollment:
Participant gender:
Summary
Background:
Dexmedetomidine, a highly selective arfa2-adrenergic agonist, is known to be a unique
sedative agent which causes less acute tolerance, drug addiction and withdrawal compared with
gamma-aminobutyrate (GABA) agonists. Dexmedetomidine was approved for short-term ICU sedation
in 2004 in Japan, and it has been used particularly for surgical ICU patients. In August 2010
dexmedetomidine was approved in Japan for sedation lasting more than 24 hours.
Recent evidence demonstrated that dexmedetomidine has organ protective effects including
neuroprotection, cardioprotection, renal protection, gastrointestinal tract action, and
anti-inflammatory action. Dexmedetomidine was shown to significantly decrease the infarct
size in isolated rat hearts. Additionally, dexmedetomidine exhibited a preconditioning effect
against ischemic injury in hippocampal slices, and this result was considered an apoptosis
suppression effect of dexmedetomidine. Aydin C et al reported that dexmedetomidine enhanced
the spontaneous contractions of the ileum in peritonitis rats compared with propofol and
midazolam. Taniguchi and colleagues demonstrated that dexmedetomidine reduced high mortality
rates and the plasma cytokine concentrations, interleukin-6 and tumor necrosis factor alpha
in endotoxemic rats.
A meta-analysis has shown that perioperative alfa2-adrenergic agonists, including
dexmedetomidine infusion, decreased cardiovascular events on patients undergoing cardiac
surgery. Dexmedetomidine treated patients undergoing thoracotomy indicated increase in urine
output, reduction in serum creatinine, and the suppression of diuretics in a randomized
placebo-controlled double-blind study. Septic patients receiving dexmedetomidine had improved
28-day mortality rates compared with septic patients receiving lorazepam in a sub-group
analysis of MENDS randomized controlled trial.
These positive effects of dexmedetomidine on the cardiovascular system, neurons, kidneys,
gastrointestinal tract action, and an anti-inflammatory action, are expected to improve
mortality in septic patients. However, large clinical research studies have not been
conducted yet. We designed and conducted the DESIRE trial (DExmedetomidine for Sepsis in ICU
Randomized Evaluation trial) to test a hypothesis that dexmedetomidine may improve clinical
outcome and has these organ protective effects on septic patients.
Objective:
To determine whether dexmedetomidine improves clinical outcome and has organ protective
effects on septic patients.
Phase:
Phase 4
Details
Lead Sponsor:
Wakayama Medical University
Collaborators:
Hirosaki University Hyogo College of Medicine Kinki University Kyoto Medical Center National Hospital Organization Kyoto Medical Center Osaka City General Hospital Osaka City University Saga University Sapporo Medical University Shimane University Tohoku University Yamaguchi Grand Medical Center