Dexmedetomidine for Sepsis in ICU Randomized Evaluation Trial (DESIRE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Wakayama Medical University
Sponsor:
Collaborators:
Kinki University
Osaka City University
Hyogo College of Medicine
Osaka City General Hospital
National Hospital Organization Kyoto Medical Center
Shimane University
Saga University
Yamaguchi Grand Medical Center
Sapporo Medical University
Information provided by (Responsible Party):
Yu Kawazoe, Wakayama Medical University
ClinicalTrials.gov Identifier:
NCT01760967
First received: December 26, 2012
Last updated: February 7, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Sepsis
Drug: Dexmedetomidine
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Wakayama Medical University:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 200
Study Start Date: January 2013
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Dexmedetomidine
administer dexmedetomidine (0.1-0.7ug/kg/h) from the beginning of ICU treatment
Drug: Dexmedetomidine
intervention to administer dexmedetomidine or not
Active Comparator: non-Dexmedetomidine
administer sedatives except Dexmedetomidine
Drug: Dexmedetomidine
intervention to administer dexmedetomidine or not

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01760967

Contacts
Contact: Yu Kawazoe +81-73-441-0603 ukz411@gmail.com
Contact: Kyohei Miyamoto +81-73-441-0603 go.go.kyohei.miyamoto@gmail.com

Locations
Japan
Wakayama Medical University Recruiting
Wakayama, Japan
Contact: Yu Kawazoe    +81-73-441-0603    ukz411@gmail.com   
Sponsors and Collaborators
Wakayama Medical University
Kinki University
Osaka City University
Hyogo College of Medicine
Osaka City General Hospital
National Hospital Organization Kyoto Medical Center
Shimane University
Saga University
Yamaguchi Grand Medical Center
Sapporo Medical University
Investigators
Study Chair: Yu Kawazoe Wakayama Medical University
Study Director: Hitoshi Yamamura, doctor Osaka City University
Study Director: Takeshi Morimoto, doctor Kinki University
  More Information

No publications provided

Responsible Party: Yu Kawazoe, lecturer, Wakayama Medical University
ClinicalTrials.gov Identifier: NCT01760967     History of Changes
Other Study ID Numbers: DESIRE, UMIN000009665
Study First Received: December 26, 2012
Last Updated: February 7, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Wakayama Medical University:
Dexmedetomidine
sepsis
mortality
duration of mechanical ventilation
organ failure

Additional relevant MeSH terms:
Sepsis
Toxemia
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Dexmedetomidine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014