Dexmedetomidine in Modifying Immune Paralysis In Patient With Septic Shock (RODIS)

ROle of Dexmedetomidine in Modifying Immune Paralysis In Patient With Septic Shock: Randomized Controlled Trial (RODIS Trial)

in this study the investigators aim to assess the role of using dexmedetomidine as sedative in septic shock patients in comparison with midazolam. The investigators aim to assess the effect on immune response and inflammatory mediators and effect on vasopressors.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Dexmedetomidine Injection [Precedex]; Drug: Midazolam

Detailed Description

Sedation protocol All patients will receive analgesia with fentanyl at fixed dose of 0.5 µg.kg.hr-1. Each patient will receive the study drug within 6 hours after ICU admission. Depth of sedation will be assessed using Richmond Agitation and Sedation Scale (RASS) scores (6), which range from -5 (unarousable) to +4 (combative). Study treatments will be infused without loading dose. Group I patients will have dexmedetomidine (4 µg.mL-1) and group II patients will have midazolam (0.33 mg.mL-1). Both drugs will be prepared in 0.9% sodium chloride in 50-mL syringe. Both the agents will be titrated to maintain the RASS in a range of -3 to -1. Dexmedetomidine infusion will be started at 0.1 µg.kg-1.hr-1 and will be adjusted by 0.1 µg.kg-1.h-1 to a maximum of 0.5 µg/kg/h, while midazolam will be started at 1 mg.h-1 (3 mL.hr-1) and adjusted by 1 mg.h-1 to a maximum of 5 mg.h-1 (15 mL.h-1). All infusions will be adjusted by increments of 3 mL/hr-1. Patients in either group not adequately sedated by study drug titration will receive a bolus dose of fentanyl 0.5-1 µg.kg. Assessment of RASS score will be performed every 2 hours and prior to any dose of rescue therapy. The study drugs will be infused for 24 hours and after that the choice of sedation will be determined according to preference of attending physician.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Kasr Alainy Hospital , Faculty of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age more than 18 years old
• All mechanically ventilated patients who will be clinically suspected of having septic shock defined by infusion of at least one vasopressor and lactate > 2.0 mmol/l (5)

Exclusion Criteria:

• Age < 18 years old
• Pregnant patient
• Source of sepsis not controlled
• Acute hepatitis or severe liver disease (Child-Pugh class C)
• Left ventricular ejection fraction less than 30%
• Heart rate less than 50 beats/min
• Second or third degree heart block
• Systolic pressure < 90 mmHg despite of infusion of 2 vasopressors.
• Psychological illness or severe cognitive dysfunction
• Patients who are allergic to dexmedetomidine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexmedetomidine Group; patients will receive dexmedetomidine as sedative	Drug: Dexmedetomidine Injection [Precedex]; Dexmedetomidine infusion will be started at 0.1 µg.kg-1.hr-1 and will be adjusted by 0.1 µg.kg-1.h-1 to a maximum of 0.5 µg/kg/h,
Active Comparator: Midazolam; patients will receive midazolam as sedative	Drug: Midazolam; midazolam will be started at 1 mg.h-1 (3 mL.hr-1) and adjusted by 1 mg.h-1 to a maximum of 5 mg.h-1 (15 mL.h-1).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CD42/CD14	Expression of CD42/CD14 will be measured by flow cytometry	24 hours after start of study drugs infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
effect on HLA-DR/CD14	Expression of HLA-DR/CD14 will be measured by flow cytometry	Baseline before start of drug then 6, 12 and 24 hour after drug
TNFα	Expression of tumor necrosis factor (TNFα) will be measured by flow cytometry	Baseline before start of drug then 6, 12 and 24 hour after drug
IL10	Interleukin 10 will be measured by flow cytometry	Baseline before start of drug then 6, 12 and 24 hour after drug
KIM-1 level	kidney injury molecule 1	Baseline before start of drug and 24 hour after drug
number of participants that will die within 28 days	mortality within 28 days	within 28 dyas

Collaborators and Investigators

• Sponsor: Kasr El Aini Hospital
• Investigators: Study Director: Ahmed Mohamed Mukhtar, M,D, kasralainy faculty of medicine, Cairo university

Publications and helpful links

General Publications

• Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.
• Biswas SK, Lopez-Collazo E. Endotoxin tolerance: new mechanisms, molecules and clinical significance. Trends Immunol. 2009 Oct;30(10):475-87. doi: 10.1016/j.it.2009.07.009. Epub 2009 Sep 24.
• Yeaman MR. Platelets in defense against bacterial pathogens. Cell Mol Life Sci. 2010 Feb;67(4):525-44. doi: 10.1007/s00018-009-0210-4. Epub 2009 Dec 15.
• Miranda ML, Balarini MM, Bouskela E. Dexmedetomidine attenuates the microcirculatory derangements evoked by experimental sepsis. Anesthesiology. 2015 Mar;122(3):619-30. doi: 10.1097/ALN.0000000000000491.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2019
• Primary Completion (Actual): February 20, 2020
• Study Completion (Actual): August 20, 2021

Study Registration Dates

• First Submitted: June 14, 2019
• First Submitted That Met QC Criteria: June 17, 2019
• First Posted (Actual): June 18, 2019

Study Record Updates

• Last Update Posted (Actual): July 19, 2022
• Last Update Submitted That Met QC Criteria: July 16, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Neurologic Manifestations; Sepsis; Shock, Septic; Shock; Paralysis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam; Dexmedetomidine
• Other Study ID Numbers: N-5-2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No