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The Effect of Vitamin C, Thiamine and Hydrocortisone on Clinical Course and Outcome in Patients With Severe Sepsis and Septic Shock

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ClinicalTrials.gov Identifier: NCT03335124
Recruitment Status : Terminated (Due to insufficient recruitment)
First Posted : November 7, 2017
Last Update Posted : February 19, 2019
Sponsor:
Information provided by (Responsible Party):
Sebastian Stefanovic, MD, University Medical Centre Ljubljana

Brief Summary:
The global burden of sepsis is substantial with an estimated 15 to 19 million cases per year; the vast majority of these cases occur in low income countries. New therapeutic approaches to sepsis are desperately required; considering the global burden of sepsis these interventions should be effective, cheap, safe and readily available. The aim is to study the synergistic effect of vitamin C, hydrocortisone and thiamine on survival in patients with severe sepsis and septic shock.

Condition or disease Intervention/treatment Phase
Sepsis Septic Shock Critical Illness Fluid Overload Drug: Vitamin C Drug: Hydrocortisone Drug: Thiamine Drug: 0.9% Sodium Chloride Injection Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Placebo-Controlled Study to Investigate the Effects of Vitamin C, Hydrocortisone and Thiamine on the Outcome of Patients With Severe Sepsis and Septic Shock
Actual Study Start Date : September 26, 2017
Actual Primary Completion Date : December 1, 2018
Actual Study Completion Date : December 1, 2018


Arm Intervention/treatment
Experimental: Active substances

Vitamin C: Vitamin C will be mixed as 1500 mg vitamin C in 50ml container, which will then be infused over 30 minutes to 1 hour. The bag will be labeled by the pharmacy as Vitamin C. The dosing schedule is 1500mg every 6 hours for 4 days or until discharge from the ICU.

Hydrocortisone: Hydrocortisone will be mixed as 50 mg of Hydrocortisone in 50 ml of 0.9 % Sodium Chloride. Patients will be treated with hydrocortisone 50mg IV q 6 hourly for 4 days or until ICU discharge.

Thiamine: Intravenous thiamine will be given in a dose of 200mg q 12 hourly for 4 days or until ICU discharge.

Drug: Vitamin C
Vitamin C: Vitamin C will be applied as per instructions described in arm/group descriptions.
Other Name: Ascorbic Acid

Drug: Hydrocortisone
Hydrocortisone: Hydrocortisone will be applied as per instructions described in arm/group descriptions.
Other Name: Corticosteroids

Drug: Thiamine
Intravenous thiamine will be applied as per instructions described in arm/group descriptions.
Other Name: B1 Vitamin

Placebo Comparator: Control
Vitamin C placebo will consist of an identical container of 50cc normal saline (0.9% Sodium Chloride Injection) (but with no vitamin C) and will be labelled vitamin C. Placebo will be infused over 30-60 minutes as per the infusion instructions of the active vitamin. Hydrocortisone placebo will be provided in an identical 50 ml bag of 0.9% Sodium Chloride Injection. Placebo patients will receive a matching vial of 0.9% Sodium Chloride Injection.
Drug: 0.9% Sodium Chloride Injection
0.9 % Sodium Chloride will be applied as placebo as per instructions described in arm/group descriptions.
Other Name: Normal Saline




Primary Outcome Measures :
  1. Hospital mortality [ Time Frame: From date of randomization till time of discharge, assessed up to 12 months ]
    We will compare mortality between the treatment and placebo groups during the hospitalization


Secondary Outcome Measures :
  1. 60 day mortality [ Time Frame: 60 days from inclusion in the study ]
    We will compare mortality between the treatment and placebo groups after 60 days after inclusion in the study

  2. 28 day mortality [ Time Frame: 28 days from inclusion in the study ]
    We will compare mortality between the treatment and placebo groups after 28 days after inclusion in the study

  3. Time to vasopressor independence [ Time Frame: Defined as the time from starting the active treatment/placebo to discontinuation of all pressors, till discharged from ICU, assessed in the first month ]
    Defined as the time from starting the active treatment/placebo to discontinuation of all pressors

  4. PCT clearance [ Time Frame: The first 4 days in Intensive Care Unit ]
    Clearance of calculated procalcitonin using the following formula: initial PCT minus PCT at 96 hours, divided by the initial PCT multiplied by 100.

  5. Delta SOFA score [ Time Frame: The first 4 days in Intensive Care Unit ]
    Delta Systemic Organ Failure Assesment score, defined as the initial SOFA score minus the day 4 SOFA score. The Sequential Organ Failure Assessment (SOFA) is a morbidity severity score and mortality estimation tool developed from a large sample of ICU patients throughout the world. The higher the value, the higher the mortality. The maximum score is 24, the lowest 0.

  6. ICU length of stay (LOS) and ICU free days. [ Time Frame: ICU free days is calculated as the number of days alive and out of the ICU to day 28 ]
    ICU free days is calculated as the number of days alive and out of the ICU to day 28

  7. Hospital Length of Stay [ Time Frame: Hospital Length of Stay through the study completion, assessed up to 12 months ]
    The length of stay in the hospital



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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:

  • Diagnosis of severe sepsis or septic shock within 12 hours of admission in our Intensive Care Unit (ICU).
  • Informed consent.

Exclusion Criteria:

  • Age < 18 years
  • Pregnancy
  • Do Not Resuscitate (DNR/DNI) with limitations of care
  • Patients with fatal underlying disease who are unlikely to survive to hospital discharge (e.g.: disseminated malignant disease)
  • Patients primarily admitted for acute coronary syndromes, acute cerebrovascular incidents or active gastrointestinal (GI) bleeds
  • Patients that need immediate surgical treatment
  • Patients with HIV and a cell count of cluster of differentiation 4 (CD4) cells < 50 mm2,
  • Patients with known glucose-6 phosphate dehydrogenase (G-6PD) deficiency.
  • Patients with severe sepsis/septic shock transferred from another hospital
  • Patients with features of sepsis/septic shock > 24 hours
  • Patients who require treatment with corticosteroids for an indication other than sepsis (chronic corticosteroid use, known Addison's Disease, Ulcerative colitis, Crohn's disease...)

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): NCT03335124


Locations
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Slovenia
Department of Gastroenterology, UMC Ljubljana
Ljubljana, Slovenia, 1000
Sponsors and Collaborators
University Medical Centre Ljubljana
Investigators
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Principal Investigator: Sebastian Stefanovic, MD University Medical Center Ljubljana, Department of Gastroenterology
  Study Documents (Full-Text)

Documents provided by Sebastian Stefanovic, MD, University Medical Centre Ljubljana:

Publications:
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Responsible Party: Sebastian Stefanovic, MD, Doctor of Medicine, University Medical Centre Ljubljana
ClinicalTrials.gov Identifier: NCT03335124     History of Changes
Other Study ID Numbers: CSEPSIS
First Posted: November 7, 2017    Key Record Dates
Last Update Posted: February 19, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All collected IPD
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: For a year after the completion of the study
Access Criteria: Contributing authors that will sign the declaration of patient data confidentiality.

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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.: No

Keywords provided by Sebastian Stefanovic, MD, University Medical Centre Ljubljana:
Sepsis
Vitamin C
Hydrocortisone
Thiamine
Critical Illness
Fluid Responsiveness
Hemodynamics

Additional relevant MeSH terms:
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Sepsis
Toxemia
Shock
Shock, Septic
Critical Illness
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
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