SepsisPhase 4DESIRENCT01760967
Dexmedetomidine for Sepsis in ICU Randomized Evaluation Trial
A Phase 4 study testing Dexmedetomidine in people with Sepsis, run by Wakayama Medical University at 1 site in Japan.
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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Dexmedetomidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 203 participants
- Where
- 1 siteJapan
- Study dates
- Jan 2013to Jan 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult
- transferred to ICU
- anticipation of a need for mechanical ventilation at least 24 hours
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read more
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
- Being tested
- Dexmedetomidine
- Keywords
- Dexmedetomidine, sepsis, mortality, duration of mechanical ventilation, organ failure
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
intervention to administer dexmedetomidine or not
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine | Active comparator | administer dexmedetomidine (0.1-0.7ug/kg/h) from the beginning of ICU treatment Receives: Drug: Dexmedetomidine |
| non-Dexmedetomidine | Active comparator | administer sedatives except Dexmedetomidine Receives: Drug: Dexmedetomidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
mortality
mortality of patients on 28 days or on a day of discharge if patients are discharged earlier than 28 days
Measured: on 28 days
duration of mechanical ventilation
duration of mechanical ventilation in the ICU involving non-invasive ventilation
Measured: up to 28 days
Secondary outcomes (12)
length of stay in the ICU
Measured: up to 28 days
length of stay in the hospital
Measured: up to 28 days
Evaluation of restlessness and delirium
evaluation of Richmond agitation-sedation scale (RASS) and Confusion Assessment Method for ICU patients (CAM-ICU)
Measured: up to 28 days in the ICU
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
Measured: on 28 days or on the day of discharge
Occurrence of arrythmia or myocardial ischemia
Measured: up to 28 days in the ICU
Renal function
blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), daily urinary output, need of renal replacement therapy
Measured: up to 28 days in the ICU
infection control
Duration of antimicrobial agents use within 28 days or a day of discharge if patients are discharged earlier than 28 days
Measured: within 28 days until discharge
inflammation marker
Laboratory marker of inflammation (CRP, PCT) on 1,3,7,14 days
Measured: for 14days
organ failure control
Sequential Organ Failure Assessment (SOFA) score during in the ICU
Measured: up to 28 days in the ICU
coagulopathy control
Disseminated Intravascular Coagulation (DIC) score by the Japanese Association for Acute Medicine during in the ICU
Measured: for 14 days
nutrition control
daily energy intake by enteral nutrition
Measured: up to 28 days in the ICU
sedation control
dose of sedative drugs and analgesic drugs during in the ICU
Measured: up to 28 days in the ICU
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2013 (estimated)
- Study startJan 2013
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 203 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wakayama Medical University
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Principal investigator, Yu Kawazoe, Tohoku University
- Investigators
- Yu Kawazoe, Study chair, Tohoku UniversityHitoshi Yamamura, doctor, Study director, Hirosaki UniversityTakeshi Morimoto, doctor, Study director, Hyogo Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01760967
- Sponsor's protocol ID
- DESIRE
- Other IDs
- UMIN000009665
- Acronym
- DESIRE
- Status last verified
- Feb 2017
- First submitted
- 26 Dec 2012
- Last updated
- 28 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 32778146Nakashima 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.
PubMed 31908779Yamamura 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.
PubMed 29497535Kawazoe 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.
PubMed 28322414Rudiger A, Singer M. Decatecholaminisation during sepsis. Crit Care. 2016 Oct 4;20(1):309. doi: 10.1186/s13054-016-1488-x. No abstract available.
PubMed 27716402
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01760967
- Acronym / sponsor ID
- DESIRE / DESIRE
- Conditions
- Sepsis
- Keywords
- Dexmedetomidine, sepsis, mortality, duration of mechanical ventilation, organ failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 203 participants (actual)
- Lead sponsor
- Wakayama Medical UniversityUniversity, hospital or other
- 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
- Study start
- Jan 2013
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 4 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine | Active comparator | Drug: Dexmedetomidineadminister dexmedetomidine (0.1-0.7ug/kg/h) from the beginning of ICU treatment |
| non-Dexmedetomidine | Active comparator | Drug: Dexmedetomidineadminister sedatives except Dexmedetomidine |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- adult
- transferred to ICU
- anticipation of a need for mechanical ventilation at least 24 hours
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dexmedetomidineintervention to administer dexmedetomidine or not | Drug | Dexmedetomidine, non-Dexmedetomidine |
Primary outcome
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
12 secondary outcomes
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 cognitive function
Time frame: on 28 days or on the day of discharge
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
infection control
Time frame: within 28 days until discharge
inflammation marker
Time frame: for 14days
organ failure control
Time frame: up to 28 days in the ICU
coagulopathy control
Time frame: for 14 days
nutrition control
Time frame: up to 28 days in the ICU
sedation control
Time frame: up to 28 days in the ICU
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2017.
- Derived from this study: PubMed 32778146Ohta 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.
- Derived from this study: PubMed 31908779Nakashima 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.
- Derived from this study: PubMed 29497535Yamamura 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.
- Derived from this study: PubMed 28322414Kawazoe 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.
- Derived from this study: PubMed 27716402Rudiger A, Singer M. Decatecholaminisation during sepsis. Crit Care. 2016 Oct 4;20(1):309. doi: 10.1186/s13054-016-1488-x. No abstract available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yu Kawazoe study chair
Tohoku University
Hitoshi Yamamura, doctor study director
Hirosaki University
Takeshi Morimoto, doctor study director
Hyogo Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dexmedetomidine in people with Sepsis, run by Wakayama Medical University at 1 site in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mortality (time frame: on 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01760967, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2017.