Dexmedetomidine for Sepsis in ICU Randomized Evaluation Trial

Sepsis Clinical Trial

— DESIRE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01760967
• Other study ID #: DESIRE
• Secondary ID: UMIN000009665
• Status: Completed
• Phase: Phase 4
• First received: December 26, 2012
• Last updated: February 25, 2017
• Start date: January 2013
• Est. completion date: January 2016

Study information

• Verified date: February 2017
• Source: Wakayama Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 203
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sepsis
• Toxemia

Intervention

Drug:
• Dexmedetomidine
intervention to administer dexmedetomidine or not

Locations

Country	Name	City	State
Japan	Tohoku University	Sendai	Miyagi

Sponsors (11)

Lead Sponsor	Collaborator
Wakayama Medical University	Hirosaki University, Hyogo College of Medicine, Kyoto Medical Center, National Hospital Organization Kyoto Medical Center, Osaka City General Hospital, Osaka City University, Saga University, Sapporo Medical University, Tohoku University, Yamaguchi Grand Medical Center

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	mortality	mortality of patients on 28 days or on a day of discharge if patients are discharged earlier than 28 days	on 28 days
Primary	duration of mechanical ventilation	duration of mechanical ventilation in the ICU involving non-invasive ventilation	up to 28 days
Secondary	length of stay in the ICU		up to 28 days
Secondary	length of stay in the hospital		up to 28 days
Secondary	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
Secondary	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
Secondary	Occurrence of arrythmia or myocardial ischemia		up to 28 days in the ICU
Secondary	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
Secondary	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
Secondary	inflammation marker	Laboratory marker of inflammation (CRP, PCT) on 1,3,7,14 days	for 14days
Secondary	organ failure control	Sequential Organ Failure Assessment (SOFA) score during in the ICU	up to 28 days in the ICU
Secondary	coagulopathy control	Disseminated Intravascular Coagulation (DIC) score by the Japanese Association for Acute Medicine during in the ICU	for 14 days
Secondary	nutrition control	daily energy intake by enteral nutrition	up to 28 days in the ICU
Secondary	sedation control	dose of sedative drugs and analgesic drugs during in the ICU	up to 28 days in the ICU