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Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS)

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ClinicalTrials.gov Identifier: NCT03509350
Recruitment Status : Recruiting
First Posted : April 26, 2018
Last Update Posted : October 16, 2018
Sponsor:
Collaborator:
The Marcus Foundation
Information provided by (Responsible Party):
Jonathan Sevransky, Emory University

Brief Summary:
The VItamin C, Thiamine And Steroids in Sepsis (VICTAS) Study is a double-blind, placebo-controlled, adaptive randomized clinical trial designed to investigate the efficacy of the combined use of vitamin C, thiamine and corticosteroids versus indistinguishable placebos for patients with sepsis. The objective of this study is to demonstrate the efficacy of combination therapy using vitamin C, thiamine and corticosteroids in reducing mortality and improving organ function in critically ill patients with sepsis.

Condition or disease Intervention/treatment Phase
Sepsis Drug: Vitamin C Drug: Thiamine Drug: Hydrocortisone Drug: Vitamin C Placebo Drug: Thiamine Placebo Drug: Hydrocortisone Placebo Phase 3

  Show Detailed Description

Study Type : Interventional
Estimated Enrollment : 2000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
Official Title: A Multi-center, Randomized, Placebo-controlled, Double-blind, Adaptive Clinical Trial of Vitamin C, Thiamine and Steroids as Combination Therapy in Patients With Sepsis.
Actual Study Start Date : August 22, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : October 2021


Arm Intervention/treatment
Experimental: Treatment Protocol
Participants randomized to the treatment protocol will receive the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.
Drug: Vitamin C
Intravenous vitamin C (1.5 grams every 6 hours) will be administered for 4 days or until ICU discharge.
Other Name: Ascorbic acid

Drug: Thiamine
Intravenous thiamine (100 mg every 6 hours) will be administered for 4 days or until ICU discharge.
Other Name: Thiamine hydrochloride

Drug: Hydrocortisone
Intravenous hydrocortisone (50 mg every 6 hours) will be administered for 4 days or until ICU discharge.
Other Name: Hydrocortisone sodium succinate

Placebo Comparator: Control Protocol
A placebo to match the VICTAS intervention will be administered for four days or until ICU discharge. During the treatment period, if an indication for steroids exist, the treating physicians are permitted to initiate open-label corticosteroid therapy based on local practice and international guidelines. If this occurs, the hydrocortisone/placebo will be withheld and subjects will be started on open-label corticosteroids.
Drug: Vitamin C Placebo
A placebo to match intravenous vitamin C (1.5 grams every 6 hours) will be administered for 4 days or until ICU discharge.
Other Name: Placebo

Drug: Thiamine Placebo
A placebo to match intravenous thiamine (100 mg every 6 hours) will be administered for 4 days or until ICU discharge.
Other Name: Placebo

Drug: Hydrocortisone Placebo
A placebo to match intravenous hydrocortisone (50 mg every 6 hours) will be administered for 4 days or until ICU discharge. Steroids will be used when clinically indicated.
Other Name: Placebo




Primary Outcome Measures :
  1. Vasopressor and ventilator-free days (VVFD) [ Time Frame: Day 30 ]
    The primary outcome measure is VVFD at 30 days (+/-3 days) after randomization. Vasopressor and ventilator-free days will be determined by recording all start and stop days of these measures.


Secondary Outcome Measures :
  1. Mortality at 30 days [ Time Frame: Day 30 ]
    The number of participants who did not survive until Day 30 will be compared between study arms.

  2. Delirium-free and coma-free days (DCFD) [ Time Frame: Day 14 ]
    Delirium and Coma-Free Days (DCFDs) is defined as the number of days between enrollment and day 14 the subject has a Richmond Agitation-Sedation Scale (RASS) -3 or higher and Confusion Assessment Method for the ICU (CAM-ICU) negative (or Brief Confusion Assessment Method (bCAM) negative if in the ED) among survivors at that time point (day 14). The RASS categorizes patient sedation level on a scale from -5 (unarousable sedation) to +4 (combative), where 0 indicates alert and calm. Delirium is diagnosed with the CAM when the patient exhibits an acute change in mental status and inattention plus either disorganized thinking or an altered level of consciousness.



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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:

  • Suspected or confirmed infection as evidenced by ordering of blood cultures and administration of at least one antimicrobial agent
  • Acute respiratory or cardiovascular organ dysfunction attributed to sepsis as evidenced by at least one of the following requirements:

    1. Vasopressor Requirement - Continuous infusion of norepinephrine, epinephrine, vasopressin, dopamine, phenylephrine or other vasopressor agents at any dose for greater than 1 hour and required to maintain a mean arterial pressure ≥ 65 mm Hg despite intravenous crystalloid infusion of at least 1000cc
    2. Respiratory Support Requirement - Acute hypoxemic respiratory failure defined as persistent hypoxemia ( partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤ 300 or blood oxygen saturation (SpO2)/FiO2 ≤ 315) requiring (1) intubation and mechanical ventilation, or (2) positive pressure ventilation via tight-fitting face mask (i.e. continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) or (3) high flow nasal cannula ≥ 45 liter per minute (LPM) flow and FiO2 ≥ 0.40
  • Anticipated or confirmed intensive care unit (ICU) admission

Exclusion Criteria:

  • Organ dysfunction present > 24 hours at time of enrollment
  • Limitations of care (defined as refusal of cardiovascular and respiratory support modes described in inclusion criteria 7.1.b) including "do not intubate" (DNI) status
  • Current hospitalization > 30 days at time of randomization
  • Chronic hypoxemia requiring supplemental non-invasive oxygen (nasal cannula or NIPPV) or home mechanical ventilation
  • Chronic cardiovascular failure requiring home mechanical hemodynamic support (e.g., LVAD) or home chemical hemodynamic support (e.g., milrinone)
  • Known allergy or contraindication to vitamin C, thiamine, and/or corticosteroids (including previously or currently diagnosed primary hyperoxaluria and/or oxalate nephropathy, or nown/suspected ethylene glycol ingestion, or known glucose-6-phosphate dehydrogenase (G6PD) deficiency)
  • Currently receiving intravenous vitamin C as a treatment for sepsis OR any dose of vitamin C exceeding 1 gram daily
  • Chronic disease/illness that, in the opinion of the site investigator, have an expected lifespan of < 30 days unrelated to current sepsis diagnosis (e.g., stage IV malignancy, neurodegenerative disease, etc.)
  • Pregnancy or known active breastfeeding
  • Prisoner or Incarceration
  • Current participation in another interventional pharmaceutical research study for sepsis
  • Inability or unwillingness of subject or legal surrogate/representative to give written informed consent

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): NCT03509350


Contacts
Contact: Jonathan Sevransky, MD, MHS 404-778-5734 jonathan.sevransky@emoryhealthcare.org

Locations
United States, Georgia
Grady Memorial Hospital Recruiting
Atlanta, Georgia, United States, 30303
Contact: Lovie Negrin       lovienegrin@emory.edu   
Contact: Carmen Polito, MD       CPOLITO@emory.edu   
Principal Investigator: Carmen Polito, MD         
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Contact: Christine Spainhour       christine.spainhour@emory.edu   
Contact: Katherine Nugent, MD       katherine.lyn.nugent@emory.edu   
Principal Investigator: Katherine Nugent, MD         
Emory Saint Joseph's Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Sonya Mathewson       sbmathe@emory.edu   
Contact: Larry Busse, MD       laurence.w.busse@emory.edu   
Principal Investigator: Larry Busse, MD         
United States, Maryland
Johns Hopkins Bayview Recruiting
Baltimore, Maryland, United States, 21224
Contact: Erin Ricketts       ericket2@jhmi.edu   
Contact: David Hager, MD, PhD       dhager1@jhmi.edu   
Principal Investigator: David Hager, MD, PhD         
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Erin Ricketts       ericket2@jhmi.edu   
Contact: Jeremiah Hinson       jeremiah.s.hinson@jhmi.edu   
Principal Investigator: Jeremiah Hinson, MD, PhD         
United States, Tennessee
Vanderbilt University Medical Center Not yet recruiting
Nashville, Tennessee, United States, 37232
Contact: Wesley Self, MD, MPH       wesley.self@Vanderbilt.Edu   
Contact: Matt Semler, MD, MSc       matthew.w.semler@vanderbilt.edu   
Principal Investigator: Wesley Self, MD, MPH         
United States, Virginia
Eastern Virginia Medical School Not yet recruiting
Norfolk, Virginia, United States, 23507
Contact: Michael H Hooper, MD, MSc       hoopermh@evms.edu   
Contact: Jennifer F May, PhD       jlfreema@sentara.com   
Principal Investigator: Michael H Hooper, MD, MSc         
Virginia Commonwealth University Not yet recruiting
Richmond, Virginia, United States, 23284
Contact: Chris DeWilde, PhD-c, RN       christine.dewilde@vcuhealth.org   
Contact: Anna Priday, MS       anna.priday@vcuhealth.org   
Principal Investigator: Berry Fowler, MD         
Sponsors and Collaborators
Emory University
The Marcus Foundation
Investigators
Principal Investigator: Jonathan Sevransky, MD, MHS Emory University

Responsible Party: Jonathan Sevransky, Professor, Emory University
ClinicalTrials.gov Identifier: NCT03509350     History of Changes
Other Study ID Numbers: IRB00102528
IRB00164053 ( Other Identifier: Johns Hopkins IRB )
First Posted: April 26, 2018    Key Record Dates
Last Update Posted: October 16, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jonathan Sevransky, Emory University:
Vitamin C
Thiamine
Corticosteroid

Additional relevant MeSH terms:
Sepsis
Toxemia
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Vitamins
Ascorbic Acid
Thiamine
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Cortisol succinate
Hydrocortisone
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Anti-Inflammatory Agents
Vitamin B Complex