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Evaluation of Hydrocortisone, Vitamin C and Thiamine for the Treatment of Septic Shock (HYVITS)

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ClinicalTrials.gov Identifier: NCT03380507
Recruitment Status : Recruiting
First Posted : December 21, 2017
Last Update Posted : April 2, 2019
Sponsor:
Information provided by (Responsible Party):
Hamad Medical Corporation

Brief Summary:

Despite recent medical advances, sepsis and septic shock remain a major cause of death. Sepsis is a syndrome with a wide array of physiologic, pathologic, and biochemical abnormalities.

Several studies have shown vitamin C have decreased the circulating pro-inflammatory cytokines and oxidative stress.Thiamine had favorable effects on pro-inflammatory cytokines, oxidative stress and cellular hypoxia.The use of hydrocortisone in combination with vitamin C will increase the transport of vitamin C into the cells; since the pro inflammatory cytokines have shown to decrease the expression of the sodium-vitamin C transporter-2 (SVCT2) while glucocorticoids increase the SVCT2 expression.

A recent small retrospective study , showed a significant decrease in mortality when patients with severe sepsis and septic shock are treated with a combination of Hydrocortisone, Vitamin C, and Thiamine. Conducting a similar study with a prospective randomized design will give clinicians all over the world more answers and will help clinicians to provide better care to millions of patients using highly safe therapeutic regimen.

The objective of the current study is to explore the clinical benefits of using a combination of hydrocortisone, vitamin C, and thiamine (triple therapy) for the management of septic shock. To achieve this objective, we will compare two alternative treatment strategies, either triple therapy or usual care in patients with septic shock.

First aim: To assess the effectiveness of the triple therapy for septic shock

Second aim: To assess the safety of triple therapy


Condition or disease Intervention/treatment Phase
Septic Shock Critical Illness Drug: Triple therapy group Phase 2 Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 212 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Open label, prospective, randomized, two-arm parallel-group trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Hydrocortisone, Vitamin C and Thiamine for the Treatment of Septic Shock
Actual Study Start Date : March 17, 2018
Estimated Primary Completion Date : April 30, 2019
Estimated Study Completion Date : May 30, 2019


Arm Intervention/treatment
Experimental: Triple therapy group

Experimental group will receive usual care according to Hamad Medical Corporation Adult Sepsis Care Pathway (CPW 10311, May 2017) PLUS triple therapy.

Triple therapy regimen:

Intravenous vitamin C (1.5 gm q 6 hourly for 4 days or until ICU discharge, whichever is earlier), hydrocortisone (50 mg q 6 hourly for 7 days or until ICU discharge, whichever is earlier, followed by a taper over 3 days) as well as intravenous thiamine (200 mg q 12 hourly for 4 days or until ICU discharge, whichever is earlier).

Drug: Triple therapy group
Refer to arms description
Other Name: Hydrocortisone, Vitamin C and Thiamine

No Intervention: Control group
Control group will receive usual care only according to Hamad Medical Corporation Adult Sepsis Care Pathway (CPW 10311, May 2017).



Primary Outcome Measures :
  1. Hospital Mortality at 60 days [ Time Frame: 60 days after randomization ]
    Patients died during hospital admission


Secondary Outcome Measures :
  1. Time to death [ Time Frame: 60 days after randomization ]
    Time to death after randomization

  2. Clinical evidence of organ dysfunction [ Time Frame: 72 hours after randomization ]

    Change in SOFA* scores from admission to 72 hours

    *SOFA score is the Sequential Organ Failure Assessment score which is a mortality prediction score that is based on the degree of dysfunction of 6 organ systems. The score is made of 6 variables, each variable representing an organ system ( respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems). Each organ system score ranges from 0 (normal) to 4 (high degree of dysfunction/failure). The SOFA score ranges from 0 (normal) to 24 (high degree of dysfunction/failure)


  3. Length of ICU stay [ Time Frame: 60 days after randomization ]
    Duration the patient stayed in the ICU

  4. Length of hospital stay [ Time Frame: 60 days after randomization ]
    Duration the patient stayed in the hospital

  5. Duration of vasopressor therapy [ Time Frame: 60 days after randomization ]
    Time to discontinuation of vasopressor therapy and the MAP is more than 65 mmHg

  6. Lactate clearance [ Time Frame: 72 hours ]
    Defined as decrease in serum lactate levels over 72 hrs

  7. Renal replacement therapy for acute kidney injury [ Time Frame: 60 days after randomization ]
    Patient needed renal replacement therapy for acute kidney injury (Yes or no for each patient in both groups)

  8. Need for Extracorporeal membrane oxygenation (ECMO) [ Time Frame: 60 days after randomization ]
    Patient started on ECMO (Yes or no for each patient in both groups)


Other Outcome Measures:
  1. Daily mean patient-day weighted blood glucose [ Time Frame: 7 days after randomization ]
    Average of all blood glucose readings for a specific patient day then averaged across all patients of the arm.

  2. Incidence of nephrolithiasis [ Time Frame: 4 days after randomization ]
    Incidence of nephrolithiasis detected on radiological studies or diagnosed by the primary care team

  3. Incidence of secondary infections [ Time Frame: 60 days after randomization ]
    Incidence of secondary infections till ICU discharge

  4. Mechanical ventilator weaning failure [ Time Frame: 60 days after randomization ]
    Failure to pass a spontaneous breathing trial or the need for reintubation within 48 hours following extubation

  5. Hypernatremia [ Time Frame: 7 days after randomization ]
    serum sodium above 145 mEq/L

  6. Hypokalemia [ Time Frame: 7 days after randomization ]
    Serum potassium below 3.5 mEq/L

  7. Hemolysis [ Time Frame: 4 days after randomization ]
    Patient had hemolysis (Yes or no for each patient in both groups)

  8. Gastrointestinal (GI) bleeding [ Time Frame: 7 days after randomization ]
    Patient had GI bleeding (Yes or no for each patient in both groups)



Information from the National Library of Medicine

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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 (above 18 years old)
  • Suspected or documented infection
  • Meeting the definition of septic shock (Sepsis 3 definitions); Patients with septic shock can be identified with a clinical construct of sepsis with persisting hypotension requiring vasopressor therapy to maintain MAP ≥65 mm Hg and having a serum lactate level >2 mmol/L despite adequate volume resuscitation.
  • Receiving norepinephrine at a dose equal or more than 0.1 µg/kg/min for more than or equal 6 hours.

Exclusion Criteria:

  • Known pregnancy(1)
  • Primary diagnosis of acute cerebral vascular event
  • Acute coronary syndrome
  • Status asthmaticus
  • Major cardiac arrhythmia
  • Active gastrointestinal hemorrhage
  • Seizure
  • Drug overdose
  • Burn or trauma
  • Requirement for immediate surgery(2)
  • Absolute neutrophil count <500 mm3
  • CD4 <50/mm³
  • Do-not-resuscitate status
  • Advanced directives restricting implementation of the protocol
  • Terminally ill patients in palliative care
  • Participation in another interventional study
  • Known allergy or contraindication to one or more of the trial medications (Vitamin C, Thiamine, or Hydrocortisone)

    1. If the pregnancy status is unknown, the pregnancy test will not be done as part of the usual care, the patient is unconscious, and consent cannot be obtained for pregnancy test; we will not enroll the patient.
    2. Patients with septic shock and requiring immediate surgery will be evaluated after surgery for inclusion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03380507


Contacts
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Contact: Adham Mohamed, PharmD 0097433634585 adhammokhtar185@hotmail.com
Contact: Mohamed Abdelaty, MD 0097455196589 mabdelaty@hamad.qa

Locations
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Qatar
Hamad Medical Corporation Recruiting
Doha, Qatar, 3050
Sponsors and Collaborators
Hamad Medical Corporation
Investigators
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Principal Investigator: Mohamed Abdelaty, MD Hamad Medical Corporation
Principal Investigator: Adham Mohamed, PharmD Hamad Medical Corporation

Publications of Results:
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. Crit Care Med. 2017 Mar;45(3):486-552. doi: 10.1097/CCM.0000000000002255.

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Responsible Party: Hamad Medical Corporation
ClinicalTrials.gov Identifier: NCT03380507     History of Changes
Other Study ID Numbers: 17207
First Posted: December 21, 2017    Key Record Dates
Last Update Posted: April 2, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Hamad Medical Corporation:
Septic Shock
Vitamin C
Thiamine
Hydrocortisone
Critically Ill

Additional relevant MeSH terms:
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Shock
Shock, Septic
Critical Illness
Pathologic Processes
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Disease Attributes
Vitamins
Ascorbic Acid
Thiamine
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Anti-Inflammatory Agents
Vitamin B Complex