Clinical trial NCT01760967: Dexmedetomidine for Sepsis in ICU Randomized Evaluation Trial
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sepsis
Keywords: Dexmedetomidine
sepsis
mortality
duration of mechanical ventilation
organ failure
Lead sponsor: Wakayama Medical University
Sponsor class: OTHER
Collaborators: name: Osaka City University
name: Hyogo Medical University
name: Osaka City General Hospital
name: National Hospital Organization Kyoto Medical Center
name: Saga University
name: Yamaguchi Grand Medical Center
name: Sapporo Medical University
name: Tohoku University
name: Hirosaki University
name: Kyoto Medical Center
First posted: 2013-01-04
Enrollment: 203
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: mortality
timeFrame: on 28 days
measure: duration of mechanical ventilation
timeFrame: up to 28 days
Secondary outcomes:
measure: length of stay in the ICU
timeFrame: up to 28 days
measure: length of stay in the hospital
timeFrame: up to 28 days
measure: Evaluation of restlessness and delirium
timeFrame: up to 28 days in the ICU
measure: Evaluation of cognitive function
timeFrame: on 28 days or on the day of discharge
measure: Occurrence of arrythmia or myocardial ischemia
timeFrame: up to 28 days in the ICU
measure: Renal function
timeFrame: up to 28 days in the ICU
measure: infection control
timeFrame: within 28 days until discharge
measure: inflammation marker
timeFrame: for 14days
measure: organ failure control
timeFrame: up to 28 days in the ICU
measure: coagulopathy control
timeFrame: for 14 days
measure: nutrition control
timeFrame: up to 28 days in the ICU
measure: sedation control
timeFrame: up to 28 days in the ICU
Other outcomes:
Locations:
city: Sendai
country: Japan
facility: Tohoku University
state: Miyagi
Study officials:
affiliation: Tohoku University
name: Yu Kawazoe
role: STUDY_CHAIR
affiliation: Hirosaki University
name: Hitoshi Yamamura, doctor
role: STUDY_DIRECTOR
affiliation: Hyogo Medical University
name: Takeshi Morimoto, doctor
role: STUDY_DIRECTOR
References:
citation: Ohta Y, Miyamoto K, Kawazoe Y, Yamamura H, Morimoto T. Effect of dexmedetomidine on inflammation in patients with sepsis requiring mechanical ventilation: a sub-analysis of a multicenter randomized clinical trial. Crit Care. 2020 Aug 10;24(1):493. doi: 10.1186/s13054-020-03207-8.
citation: Nakashima T, Miyamoto K, Shima N, Kato S, Kawazoe Y, Ohta Y, Morimoto T, Yamamura H; DESIRE Trial Investigators. Dexmedetomidine improved renal function in patients with severe sepsis: an exploratory analysis of a randomized controlled trial. J Intensive Care. 2020 Jan 2;8:1. doi: 10.1186/s40560-019-0415-z. eCollection 2020.
citation: Yamamura H, Kawazoe Y, Miyamoto K, Yamamoto T, Ohta Y, Morimoto T. Effect of norepinephrine dosage on mortality in patients with septic shock. J Intensive Care. 2018 Feb 26;6:12. doi: 10.1186/s40560-018-0280-1. eCollection 2018.
citation: Kawazoe Y, Miyamoto K, Morimoto T, Yamamoto T, Fuke A, Hashimoto A, Koami H, Beppu S, Katayama Y, Itoh M, Ohta Y, Yamamura H; Dexmedetomidine for Sepsis in Intensive Care Unit Randomized Evaluation (DESIRE) Trial Investigators. Effect of Dexmedetomidine on Mortality and Ventilator-Free Days in Patients Requiring Mechanical Ventilation With Sepsis: A Randomized Clinical Trial. JAMA. 2017 Apr 4;317(13):1321-1328. doi: 10.1001/jama.2017.2088.
citation: Rudiger A, Singer M. Decatecholaminisation during sepsis. Crit Care. 2016 Oct 4;20(1):309. doi: 10.1186/s13054-016-1488-x. No abstract available.