Clinical trial NCT03989609: Dexmedetomidine in Modifying Immune Paralysis In Patient With Septic Shock
Official title: ROle of Dexmedetomidine in Modifying Immune Paralysis In Patient With Septic Shock: Randomized Controlled Trial (RODIS Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Septic Shock
Lead sponsor: Kasr El Aini Hospital
Sponsor class: OTHER
First posted: 2019-06-18
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in CD42/CD14
timeFrame: 24 hours after start of study drugs infusion
Secondary outcomes:
measure: effect on HLA-DR/CD14
timeFrame: Baseline before start of drug then 6, 12 and 24 hour after drug
measure: TNFα
timeFrame: Baseline before start of drug then 6, 12 and 24 hour after drug
measure: IL10
timeFrame: Baseline before start of drug then 6, 12 and 24 hour after drug
measure: KIM-1 level
timeFrame: Baseline before start of drug and 24 hour after drug
measure: number of participants that will die within 28 days
timeFrame: within 28 dyas
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Kasr Alainy Hospital , Faculty of Medicine
Study officials:
affiliation: kasralainy faculty of medicine, Cairo university
name: Ahmed Mohamed Mukhtar, M,D
role: STUDY_DIRECTOR
References:
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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.
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