- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06169475
Effect of Dexmedetomidine vs Esmolol or Placebo on Cerebral Hemodynamics in Septic Shock
December 5, 2023 updated by: Xinchen Wang
Effect of Dexmedetomidine vs Esmolol or Placebo on Cerebral Hemodynamics in Septic Shock: A Randomized Clinical Trial.
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.
Some researchers proposed that the dysregulated response or organ dysfunction can be lessened by reducing the stress response, which further reduce complication and mortality rates of sepsis.
Dexmedetomidine is alpha adrenergic receptor agonist, presenting sympatholytic action in certain parts of the brain with anxiolytic, sedative, and pain killing effects.
In the experiments of sepsis animal model, dexmedetomidine have been proved to improve serum lactate clearance and the microcirculation.
Dexmedetomidine may inhibit inflammation, as it enhances the activity of the immune system while reducing its systemic reaction and lowering cytokine concentrations.
There are also evidences in clinical trials with definite safety that dexmedetomidine reduced inflammation, reduced vasopressor requirements and improved organ function.
The beta antagonist esmolol has been proposed as a therapy to lower heart rate, thereby improving diastolic filling time, and improving cardiac output, resulting in a reduction in vasopressor support.
A recent meta-analysis of 8 randomized studies using esmolol suggested that the 32% risk ratio decreased 28-day mortality, and a meta-analysis of 7 studies using esmolol in patients with sepsis and septic shock was associated with 32% lower 28-day mortality.
However, the effect of anti-stress drugs on cerebral hemodynamics is unknown.
In this study, investigators are going to apply the technique of transcranial Doppler to assess the reaction of cerebral blood flow in anti-stress group and control group.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
It is a single-blinded, single-center, randomized trial.
Patients with septic shock established within 24 hours in the ICU of Tibet Autonomous Region People's Hospital will be screened for recruitment.
After adequate fluid resuscitation, continuous infusion of norepinephrine is given to the patients to maintain a mean arterial pressure (MAP) of 65-75 millimeter of mercury (mmHg).
Midazolam and fentanyl are given to achieve the goal sedation of bispectral index (BIS) 40-60, patients who are still with tachycardia (heart rate over 100 b.p.m.) will be recruited.
After recruitment, patients in accordance with the random number table are divided into dexmedetomidine group, esmolol group and control group (T0).
Patients in the two experimental groups are required to achieve the heart rate goal of 75-95 b.p.m. in one hour by adjusting the dose of dexmedetomidine or esmolol every twenty minutes.
All patients acquired the hemodynamic evaluation at T1, T2, T3, T4 (6, 12, 18, 24hours after enrollment).
The hemodynamic evaluation including transcranial Doppler of middle cerebral artery(MCA), deep middle cerebral vein (DMCV), basal vein Rosenthal (BVR) and transverse sinus (TS), hemodynamic parameters acquired by the pressure-recording analytical method through peripheral arterial with Mostcare.
Demographic characteristics, diagnosis, laboratory reports and drug dose are collected during the study.
Study Type
Interventional
Enrollment (Actual)
14
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
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Beijing, China
- Peking Union Medical College Hospital, Chinese Academy of Medical Science
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 18 ~ 80 years old.
- Patients established septic shock according to sepsis 3.0 criteria.
- Under deep sedation of BIS 40-60 with midazolam and fentanyl.
- After achieving the goal sedation, patients are still with tachycardia (heart rate over 100 b.p.m..
Exclusion Criteria:
- Pregnancy.
- Patients with severe arrhythmia.
- Patients with aortic or aortic valve disease.
- Patients with mechanical circulatory assist device (e.g. extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), etc).
- Patients with cerebral trauma.
- Any contraindication to the use of transcranial doppler.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
No Intervention: control group
|
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Experimental: dexmedetomidine group
|
The continuous intravenous infusion of dexmedetomidine (0.1mg/ml) will start at 0.1ug/kg/h, increasing every 20 minutes by a step change of 0.05-0.2ug/kg/h to reach the target heart rate with the expectation that this should be within 12 hours.
The infusion will be reduced by step change, and if necessary, ultimately stopped if the heart rate fall below 80b.p.m..
|
Experimental: esmolol group
|
The continuous intravenous infusion of esmolol (10mg/ml) will start at 20mg/h, increasing every 20 minutes by a step change of 20mg/h to reach the target heart rate with the expectation that this should be within 12 hours.
The infusion will be reduced by step change, and if necessary, ultimately stop if the heart rate fall below 80b.p.m..
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The cerebral hemodynamic change caused by the anti-stress therapy
Time Frame: Hour 0, Hour 6, Hour 12, Hour 18 and Hour 24.
|
The cerebral hemodynamics will be evaluated according to the features of the blood flow of MCA, DMCV, BVR and TS measured by transcranial doppler, as well as regional cerebral oxygen saturation measured by the near infrared spectroscopy at Hour 0, Hour 6, Hour 12, Hour 18 and Hour 24.
The difference will be acquired by contrasting between two intervention group and one control group.
|
Hour 0, Hour 6, Hour 12, Hour 18 and Hour 24.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The systemic hemodynamic change caused by anti-stress therapy
Time Frame: Hour 0, Hour 6, Hour 12, Hour 18 and Hour 24
|
The systemic hemodynamic changes will be acquired through the pressure-recording analytical method with Mostcare, blood pressure and electro cardiac monitor, central venous pressure (CVP) monitor, trans thoracic echocardiography, and blood gas at Hour 0, Hour 6, Hour 12, Hour 18 and Hour 24.
The difference will be acquired by contrasting between two intervention group and one control group
|
Hour 0, Hour 6, Hour 12, Hour 18 and Hour 24
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Wei Du, M.D., Peking Union Medical College Hospital
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
- Du W, Liu D, Long Y, Wang X. The beta-Blocker Esmolol Restores the Vascular Waterfall Phenomenon After Acute Endotoxemia. Crit Care Med. 2017 Dec;45(12):e1247-e1253. doi: 10.1097/CCM.0000000000002721.
- Dardalas I, Stamoula E, Rigopoulos P, Malliou F, Tsaousi G, Aidoni Z, Grosomanidis V, Milonas A, Papazisis G, Kouvelas D, Pourzitaki C. Dexmedetomidine effects in different experimental sepsis in vivo models. Eur J Pharmacol. 2019 Aug 5;856:172401. doi: 10.1016/j.ejphar.2019.05.030. Epub 2019 May 17.
- 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.
- Scibelli G, Maio L, Sasso M, Lanza A, Savoia G. Dexmedetomidine: Current Role in Burn ICU. Transl Med UniSa. 2017 Jul 1;16:1-10. eCollection 2017 Jan.
- 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.
- Zhang J, Chen C, Liu Y, Yang Y, Yang X, Yang J. Benefits of esmolol in adults with sepsis and septic shock: An updated meta-analysis of randomized controlled trials. Medicine (Baltimore). 2022 Jul 8;101(27):e29820. doi: 10.1097/MD.0000000000029820.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 1, 2020
Primary Completion (Actual)
November 1, 2021
Study Completion (Actual)
November 1, 2023
Study Registration Dates
First Submitted
November 27, 2023
First Submitted That Met QC Criteria
December 5, 2023
First Posted (Estimated)
December 13, 2023
Study Record Updates
Last Update Posted (Estimated)
December 13, 2023
Last Update Submitted That Met QC Criteria
December 5, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Infections
- Systemic Inflammatory Response Syndrome
- Inflammation
- Sepsis
- Shock, Septic
- Shock
- Physiological Effects of Drugs
- Adrenergic beta-Antagonists
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Adrenergic alpha-2 Receptor Agonists
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Hypnotics and Sedatives
- Adrenergic beta-1 Receptor Antagonists
- Dexmedetomidine
- Esmolol
Other Study ID Numbers
- D-E-P-sepsis
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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