Dexmedetomidine for Sepsis in ICU Randomized Evaluation Trial

Study Overview
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Brief Summary
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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.

Official Title
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Effect of Dexmedetomidine on Mortality, Duration of Mechanical Ventilation and Multi-organ Function in Sepsis Patients Under Lighter Sedation by Randomized Control Trial

Conditions
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Sepsis

Intervention / Treatment
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* Drug: Dexmedetomidine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dexmedetomidine<br>administer dexmedetomidine (0.1-0.7ug/kg/h) from the beginning of ICU treatment | Drug: Dexmedetomidine<br>* intervention to administer dexmedetomidine or not<br>|
| Active Comparator: non-Dexmedetomidine<br>administer sedatives except Dexmedetomidine | Drug: Dexmedetomidine<br>* intervention to administer dexmedetomidine or not<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality | mortality of patients on 28 days or on a day of discharge if patients are discharged earlier than 28 days | on 28 days | 
| duration of mechanical ventilation | duration of mechanical ventilation in the ICU involving non-invasive ventilation | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | evaluation of Richmond agitation-sedation scale (RASS) and Confusion Assessment Method for ICU patients (CAM-ICU) | up to 28 days in the ICU | 
| Evaluation of cognitive function | 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 | on 28 days or on the day of discharge | 
| Occurrence of arrythmia or myocardial ischemia |  | up to 28 days in the ICU | 
| Renal function | blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), daily urinary output, need of renal replacement therapy | up to 28 days in the ICU | 
| infection control | Duration of antimicrobial agents use within 28 days or a day of discharge if patients are discharged earlier than 28 days | within 28 days until discharge | 
| inflammation marker | Laboratory marker of inflammation (CRP, PCT) on 1,3,7,14 days | for 14days | 
| organ failure control | Sequential Organ Failure Assessment (SOFA) score during in the ICU | up to 28 days in the ICU | 
| coagulopathy control | Disseminated Intravascular Coagulation (DIC) score by the Japanese Association for Acute Medicine during in the ICU | for 14 days | 
| nutrition control | daily energy intake by enteral nutrition | up to 28 days in the ICU | 
| sedation control | dose of sedative drugs and analgesic drugs during in the ICU | up to 28 days in the ICU | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dexmedetomidine, sepsis, mortality, duration of mechanical ventilation, organ failure