Dexmedetomidine in Modifying Immune Paralysis In Patient With Septic Shock

Septic Shock Clinical Trial

— RODIS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03989609
• Other study ID #: N-5-2019
• Status: Completed
• Phase: Phase 2
• Start date: June 20, 2019
• Est. completion date: August 20, 2021

Study information

• Verified date: July 2022
• Source: Kasr El Aini Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 20, 2021
• Est. primary completion date: February 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Paralysis
• Septic Shock
• Shock
• Shock, Septic

Intervention

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,
• 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).

Locations

Country	Name	City	State
Egypt	Kasr Alainy Hospital , Faculty of Medicine	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Kasr El Aini Hospital

Country where clinical trial is conducted

Egypt, 

References & Publications (4)

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in CD42/CD14	Expression of CD42/CD14 will be measured by flow cytometry	24 hours after start of study drugs infusion
Secondary	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
Secondary	TNFa	Expression of tumor necrosis factor (TNFa) will be measured by flow cytometry	Baseline before start of drug then 6, 12 and 24 hour after drug
Secondary	IL10	Interleukin 10 will be measured by flow cytometry	Baseline before start of drug then 6, 12 and 24 hour after drug
Secondary	KIM-1 level	kidney injury molecule 1	Baseline before start of drug and 24 hour after drug
Secondary	number of participants that will die within 28 days	mortality within 28 days	within 28 dyas