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出境医 / 临床实验 / Dexmedetomidine in Modifying Immune Paralysis In Patient With Septic Shock (RODIS)

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

Study Description
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.

Condition or disease Intervention/treatment Phase
Septic Shock Drug: Dexmedetomidine Injection [Precedex] Drug: Midazolam Phase 2

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 Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: ROle of Dexmedetomidine in Modifying Immune Paralysis In Patient With Septic Shock: Randomized Controlled Trial (RODIS Trial)
Estimated Study Start Date : June 20, 2019
Estimated Primary Completion Date : February 20, 2020
Estimated Study Completion Date : March 20, 2020
Arms and Interventions
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).
Outcome Measures
Primary Outcome Measures :
  1. Change in CD42/CD14 [ Time Frame: 24 hours after start of study drugs infusion ]
    Expression of CD42/CD14 will be measured by flow cytometry


Secondary Outcome Measures :
  1. effect on HLA-DR/CD14 [ Time Frame: Baseline before start of drug then 6, 12 and 24 hour after drug ]
    Expression of HLA-DR/CD14 will be measured by flow cytometry

  2. TNFα [ Time Frame: Baseline before start of drug then 6, 12 and 24 hour after drug ]
    Expression of tumor necrosis factor (TNFα) will be measured by flow cytometry

  3. IL10 [ Time Frame: Baseline before start of drug then 6, 12 and 24 hour after drug ]
    Interleukin 10 will be measured by flow cytometry

  4. KIM-1 level [ Time Frame: Baseline before start of drug and 24 hour after drug ]
    kidney injury molecule 1

  5. number of participants that will die within 28 days [ Time Frame: within 28 dyas ]
    mortality within 28 days


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Mohamed Elayashy Mohamed Ahmed Hassan, M.D, FCAI 00201001833155 mohamedelayashy@kasralainy.edu.eg
Contact: amr hussien Sayed, M.D 00201223657694

Locations
Layout table for location information
Egypt
Kasr Alainy Hospital , Faculty of Medicine Recruiting
Cairo, Egypt
Contact: Mohamed Elayashy Mohamed Ahmed Hassan, M.D, FCAI    00201001833155    mohamedelayashy@kasralainy.edu.eg   
Sponsors and Collaborators
Kasr El Aini Hospital
Investigators
Layout table for investigator information
Study Director: Ahmed Mohamed Mukhtar, M,D kasralainy faculty of medicine, Cairo university
Tracking Information
First Submitted Date  ICMJE June 14, 2019
First Posted Date  ICMJE June 18, 2019
Last Update Posted Date June 25, 2019
Estimated Study Start Date  ICMJE June 20, 2019
Estimated Primary Completion Date February 20, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2019) 		Change in CD42/CD14 [ Time Frame: 24 hours after start of study drugs infusion ]
Expression of CD42/CD14 will be measured by flow cytometry
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2019)
  • effect on HLA-DR/CD14 [ Time Frame: Baseline before start of drug then 6, 12 and 24 hour after drug ]
    Expression of HLA-DR/CD14 will be measured by flow cytometry
  • TNFα [ Time Frame: Baseline before start of drug then 6, 12 and 24 hour after drug ]
    Expression of tumor necrosis factor (TNFα) will be measured by flow cytometry
  • IL10 [ Time Frame: Baseline before start of drug then 6, 12 and 24 hour after drug ]
    Interleukin 10 will be measured by flow cytometry
  • KIM-1 level [ Time Frame: Baseline before start of drug and 24 hour after drug ]
    kidney injury molecule 1
  • number of participants that will die within 28 days [ Time Frame: within 28 dyas ]
    mortality within 28 days
Original Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2019)
  • effect on HLA-DR/CD14 [ Time Frame: Baseline before start of drug then 6, 12 and 24 hour after drug ]
    Expression of HLA-DR/CD14 will be measured by flow cytometry
  • TNFα [ Time Frame: Baseline before start of drug then 6, 12 and 24 hour after drug ]
    Expression of tumor necrosis factor (TNFα) will be measured by flow cytometry
  • IL10 [ Time Frame: Baseline before start of drug then 6, 12 and 24 hour after drug ]
    Interleukin 10 will be measured by flow cytometry
  • KIM-1 level [ Time Frame: Baseline before start of drug and 24 hour after drug ]
    kidney injury molecule 1
  • 28-day mortality [ Time Frame: within 28 dyas ]
    mortality within 28 days
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dexmedetomidine in Modifying Immune Paralysis In Patient With Septic Shock
Official Title  ICMJE ROle of Dexmedetomidine in Modifying Immune Paralysis In Patient With Septic Shock: Randomized Controlled Trial (RODIS Trial)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Septic Shock
Intervention  ICMJE
  • 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,
  • 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).
Study Arms  ICMJE
  • Experimental: Dexmedetomidine Group
    patients will receive dexmedetomidine as sedative
    Intervention: Drug: Dexmedetomidine Injection [Precedex]
  • Active Comparator: Midazolam
    patients will receive midazolam as sedative
    Intervention: Drug: Midazolam
Publications *
  • 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.
  • 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.
  • 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.
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 17, 2019) 		40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 20, 2020
Estimated Primary Completion Date February 20, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Egypt
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03989609
Other Study ID Numbers  ICMJE N-5-2019
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Mohamed Elayashy Mohamed Ahmed Hassan, Kasr El Aini Hospital
Study Sponsor  ICMJE Kasr El Aini Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ahmed Mohamed Mukhtar, M,D kasralainy faculty of medicine, Cairo university
PRS Account Kasr El Aini Hospital
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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