Dexmedetomidine for Sepsis in ICU Randomized Evaluation Trial
- Registration Number
- NCT01760967
- Lead Sponsor
- Wakayama Medical University
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 203
- adult
- transferred to ICU
- anticipation of a need for mechanical ventilation at least 24 hours
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description non-Dexmedetomidine Dexmedetomidine administer sedatives except Dexmedetomidine Dexmedetomidine Dexmedetomidine administer dexmedetomidine (0.1-0.7ug/kg/h) from the beginning of ICU treatment
- Primary Outcome Measures
Name Time Method mortality on 28 days mortality of patients on 28 days or on a day of discharge if patients are discharged earlier than 28 days
duration of mechanical ventilation up to 28 days duration of mechanical ventilation in the ICU involving non-invasive ventilation
- Secondary Outcome Measures
Name Time Method length of stay in the ICU up to 28 days length of stay in the hospital up to 28 days Evaluation of restlessness and delirium up to 28 days in the ICU evaluation of Richmond agitation-sedation scale (RASS) and Confusion Assessment Method for ICU patients (CAM-ICU)
Evaluation of cognitive function on 28 days or on the day of discharge evaluation of Mini mental state examination (MMSE) on the 28 days or on a day of discharge if patients are discharged earlier than 28 days
infection control within 28 days until discharge Duration of antimicrobial agents use within 28 days or a day of discharge if patients are discharged earlier than 28 days
inflammation marker for 14days Laboratory marker of inflammation (CRP, PCT) on 1,3,7,14 days
organ failure control up to 28 days in the ICU Sequential Organ Failure Assessment (SOFA) score during in the ICU
coagulopathy control for 14 days Disseminated Intravascular Coagulation (DIC) score by the Japanese Association for Acute Medicine during in the ICU
nutrition control up to 28 days in the ICU daily energy intake by enteral nutrition
sedation control up to 28 days in the ICU dose of sedative drugs and analgesic drugs during in the ICU
Renal function up to 28 days in the ICU blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), daily urinary output, need of renal replacement therapy
Occurrence of arrythmia or myocardial ischemia up to 28 days in the ICU
Trial Locations
- Locations (1)
Tohoku University
🇯🇵Sendai, Miyagi, Japan
Tohoku University🇯🇵Sendai, Miyagi, Japan