Dexmedetomidine for Sepsis in ICU Randomized Evaluation Trial (DESIRE)

• ClinicalTrials.gov Identifier: NCT01760967
• Recruitment Status: Completed
• First Posted: January 4, 2013
• Last Update Posted: February 28, 2017
• Sponsor: Wakayama Medical University
• Collaborators: Osaka City University; Hyogo Medical University; Osaka City General Hospital; National Hospital Organization Kyoto Medical Center; Saga University; Yamaguchi Grand Medical Center; Sapporo Medical University; Tohoku University; Hirosaki University; Kyoto Medical Center
• Information provided by (Responsible Party): Yu Kawazoe, Tohoku University

Tracking Information

• First Submitted Date: December 26, 2012
• First Posted Date: January 4, 2013
• Last Update Posted Date: February 28, 2017
• Study Start Date: January 2013
• Actual Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 2, 2013)

• mortality [ Time Frame: on 28 days ]
  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 ]
  duration of mechanical ventilation in the ICU involving non-invasive ventilation

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 2, 2013)

• length of stay in the ICU [ Time Frame: up to 28 days ]
• length of stay in the hospital [ Time Frame: up to 28 days ]
• Evaluation of restlessness and delirium [ Time Frame: up to 28 days in the ICU ]
  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 ]
  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 ]
• Renal function [ Time Frame: up to 28 days in the ICU ]
  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 ]
  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 ]
  Laboratory marker of inflammation (CRP, PCT) on 1,3,7,14 days
• organ failure control [ Time Frame: up to 28 days in the ICU ]
  Sequential Organ Failure Assessment (SOFA) score during in the ICU
• coagulopathy control [ Time Frame: for 14 days ]
  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 ]
  daily energy intake by enteral nutrition
• sedation control [ Time Frame: up to 28 days in the ICU ]
  dose of sedative drugs and analgesic drugs during in the ICU

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Sepsis

Intervention

Drug: Dexmedetomidine

intervention to administer dexmedetomidine or not

Study Arms

• Active Comparator: Dexmedetomidine
  administer dexmedetomidine (0.1-0.7ug/kg/h) from the beginning of ICU treatment
  Intervention: Drug: Dexmedetomidine
• Active Comparator: non-Dexmedetomidine
  administer sedatives except Dexmedetomidine
  Intervention: Drug: Dexmedetomidine

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 29, 2016): 203
• Original Estimated Enrollment (submitted: January 2, 2013): 200
• Actual Study Completion Date: January 2016
• Actual Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT01760967
• Other Study ID Numbers: DESIRE; UMIN000009665 ( Other Identifier: UMIN-CTR )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Yu Kawazoe, Tohoku University
• Original Responsible Party: Yu Kawazoe, Wakayama Medical University, lecturer
• Current Study Sponsor: Wakayama Medical University
• Original Study Sponsor: Same as current

Collaborators

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

Investigators

• Study Chair: Yu Kawazoe; Tohoku University
• Study Director: Hitoshi Yamamura, doctor; Hirosaki University
• Study Director: Takeshi Morimoto, doctor; Hyogo Medical University

• PRS Account: Wakayama Medical University
• Verification Date: February 2017