Dexmedetomidine for Sepsis in ICU Randomized Evaluation Trial

NCT01760967 | Completed Phase 4 DMC

• 2 other identifiers: DESIREUMIN000009665
• Study Type: interventional
• Target: 203
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis

Keywords

Dexmedetomidine; sepsis; mortality; duration of mechanical ventilation; organ failure

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (12)

• 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

  up to 28 days in the ICU

• Evaluation of cognitive function

  on 28 days or on the day of discharge

• Occurrence of arrythmia or myocardial ischemia

  up to 28 days in the ICU

Study Arms (2)

Dexmedetomidine

ACTIVE COMPARATOR

administer dexmedetomidine (0.1-0.7ug/kg/h) from the beginning of ICU treatment

Drug: Dexmedetomidine

non-Dexmedetomidine

ACTIVE COMPARATOR

administer sedatives except Dexmedetomidine

Drug: Dexmedetomidine

Interventions

Dexmedetomidine DRUG

intervention to administer dexmedetomidine or not

Dexmedetomidine; non-Dexmedetomidine

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adult
• transferred to ICU
• anticipation of a need for mechanical ventilation at least 24 hours

You may not qualify if:

• 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

Sponsors & Collaborators

• Wakayama Medical University: lead
• Osaka City University: collaborator
• Hyogo Medical University: collaborator
• Osaka City General Hospital: collaborator
• National Hospital Organization Kyoto Medical Center: collaborator
• Saga University: collaborator
• Yamaguchi Grand Medical Center: collaborator
• Sapporo Medical University: collaborator
• Tohoku University: collaborator
• Hirosaki University: collaborator
• Kyoto Medical Center: collaborator

Study Sites (1)

Tohoku University

Sendai, Miyagi, 9808574, Japan

Location

Related Publications (5)

• 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.

  PMID: 32778146 DERIVED

• 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.

  PMID: 31908779 DERIVED

• 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.

  PMID: 29497535 DERIVED

• 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.

  PMID: 28322414 DERIVED

• 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.

  PMID: 27716402 DERIVED

MeSH Terms

Conditions

Sepsis

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Yu Kawazoe

  Tohoku University

  STUDY CHAIR

• Hitoshi Yamamura, doctor

  Hirosaki University

  STUDY DIRECTOR

• Takeshi Morimoto, doctor

  Hyogo Medical University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 26, 2012
• First Posted: January 4, 2013
• Study Start: January 1, 2013
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: February 28, 2017

Record last verified: 2017-02

Locations

JP (1)