Dexmedetomidine for Sepsis in ICU Randomized Evaluation Trial (DESIRE)
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.
To determine whether dexmedetomidine improves clinical outcome and has organ protective effects on septic patients.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Effect of Dexmedetomidine on Mortality, Duration of Mechanical Ventilation and Multi-organ Function in Sepsis Patients Under Lighter Sedation by Randomized Control Trial|
- mortality [ Time Frame: on 28 days ] [ Designated as safety issue: Yes ]mortality of patients on 28 days or on a day of discharge if patients are discharged earlier than 28 days
- duration of mechanical ventilation [ Time Frame: up to 28 days ] [ Designated as safety issue: No ]duration of mechanical ventilation in the ICU involving non-invasive ventilation
- length of stay in the ICU [ Time Frame: up to 28 days ] [ Designated as safety issue: No ]
- length of stay in the hospital [ Time Frame: up to 28 days ] [ Designated as safety issue: No ]
- Evaluation of restlessness and delirium [ Time Frame: up to 28 days in the ICU ] [ Designated as safety issue: No ]evaluation of Richmond agitation-sedation scale (RASS) and Confusion Assessment Method for ICU patients (CAM-ICU)
- Evaluation of cognitive function [ Time Frame: on 28 days or on the day of discharge ] [ Designated as safety issue: No ]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
- Occurrence of arrythmia or myocardial ischemia [ Time Frame: up to 28 days in the ICU ] [ Designated as safety issue: Yes ]
- Renal function [ Time Frame: up to 28 days in the ICU ] [ Designated as safety issue: Yes ]blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), daily urinary output, need of renal replacement therapy
- infection control [ Time Frame: within 28 days until discharge ] [ Designated as safety issue: No ]Duration of antimicrobial agents use within 28 days or a day of discharge if patients are discharged earlier than 28 days
- inflammation marker [ Time Frame: for 14days ] [ Designated as safety issue: No ]Laboratory marker of inflammation (CRP, PCT) on 1,3,7,14 days
- organ failure control [ Time Frame: up to 28 days in the ICU ] [ Designated as safety issue: No ]Sequential Organ Failure Assessment (SOFA) score during in the ICU
- coagulopathy control [ Time Frame: for 14 days ] [ Designated as safety issue: No ]Disseminated Intravascular Coagulation (DIC) score by the Japanese Association for Acute Medicine during in the ICU
- nutrition control [ Time Frame: up to 28 days in the ICU ] [ Designated as safety issue: No ]daily energy intake by enteral nutrition
- sedation control [ Time Frame: up to 28 days in the ICU ] [ Designated as safety issue: No ]dose of sedative drugs and analgesic drugs during in the ICU
|Study Start Date:||January 2013|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Active Comparator: Dexmedetomidine
administer dexmedetomidine (0.1-0.7ug/kg/h) from the beginning of ICU treatment
intervention to administer dexmedetomidine or not
Active Comparator: non-Dexmedetomidine
administer sedatives except Dexmedetomidine
intervention to administer dexmedetomidine or not
|Contact: Yu Kawazoeemail@example.com|
|Contact: Kyohei Miyamotofirstname.lastname@example.org|
|Wakayama Medical University||Recruiting|
|Contact: Yu Kawazoe +81-73-441-0603 email@example.com|
|Study Chair:||Yu Kawazoe||Wakayama Medical University|
|Study Director:||Hitoshi Yamamura, doctor||Osaka City University|
|Study Director:||Takeshi Morimoto, doctor||Kinki University|