Dexmedetomidine for Sepsis in ICU Randomized Evaluation Trial (DESIRE)

Wakayama Medical University

Status and phase: Completed; Phase 4

Conditions: Sepsis

Treatments: Drug: Dexmedetomidine

Study type: Interventional

Funder types: Other

Identifiers

NCT01760967

DESIRE

UMIN000009665 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 203 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• adult
• transferred to ICU
• anticipation of a need for mechanical ventilation at least 24 hours

Exclusion criteria

• sever chronic liver disease (Child B or C)
• acute myocardial infarction, heart disease (NYHA 4)
• Drug dependence, alcoholism
• Psychological illness, severe cognitive dysfunction
• patients who have allergy for dexmedetomidine
• attending physician's decision

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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203 participants in 2 patient groups

Dexmedetomidine

Active Comparator group

Description:

administer dexmedetomidine (0.1-0.7ug/kg/h) from the beginning of ICU treatment

Treatment:

Drug: Dexmedetomidine

non-Dexmedetomidine

Active Comparator group

Description:

administer sedatives except Dexmedetomidine

Treatment:

Drug: Dexmedetomidine