Vitamin C, Thiamine, and Steroids in Sepsis



Status:Recruiting
Conditions:Hospital
Therapuetic Areas:Other
Healthy:No
Age Range:18 - Any
Updated:3/8/2019
Start Date:August 22, 2018
End Date:October 2021
Contact:Jonathan Sevransky, MD, MHS
Email:jonathan.sevransky@emoryhealthcare.org
Phone:404-778-5734

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A Multi-center, Randomized, Placebo-controlled, Double-blind, Adaptive Clinical Trial of Vitamin C, Thiamine and Steroids as Combination Therapy in Patients With Sepsis.

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.

Sepsis is an inflammatory syndrome with life threatening organ dysfunction resulting from a
dysregulated host response to infection. The global burden is estimated to exceed 15 million
cases annually. In the United States, the incidence is increasing and currently there are
more 1,750,000 cases each year, with more than half requiring intensive care unit (ICU)
admission. Further, sepsis cases account for 30%- 50% of all hospital deaths, making it the
3rd leading cause of death in the United States, and is the most expensive reason for
hospitalization with annual expenditures exceeding $20 billion. Notably, even among those
that do survive, many endure significant reductions in physical, emotional and cognitive
quality of life. New therapeutic approaches to reduce the high morbidity and mortality of
sepsis are needed.

Current management strategies focus on early aggressive fluid resuscitation, blood pressure
support with vasopressors, early appropriate antibiotics, and the identification and control
of infected sites. Though outcomes have improved with the bundled deployment of these
strategies, mortality remains high at 20 - 30%. Despite over a hundred phase 2 and phase 3
clinical trials of pharmacological agents with the potential to improve sepsis outcomes, only
antibiotics have demonstrated reproducible benefits.

The purpose of the current study is therefore to determine (or confirm) the efficacy of the
combination therapy consisting of vitamin C, thiamine, and corticosteroids in the management
of patients with circulatory and/or respiratory dysfunction resulting from sepsis. This
subset of sepsis patients has been chosen because they are easily identified, have a high
mortality, and consume significant critical care resources. As such, any improvements in
outcomes attributed to effective therapies would be of great value to patients, as well as
their care providers and healthcare systems. Further, because the promulgated therapies are
composed of three inexpensive and readily available drugs, its efficacy would have important
implications the management of sepsis in both well and poorly resourced settings worldwide.

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 (the Treatment Protocol)
versus indistinguishable placebos (the Control Protocol) for patients with sepsis. The trial
will enroll up to 2000 participant and employs a novel endpoint that approximates a patient's
risk of death based on the time spent on vasopressors or receiving respiratory support. Time
spent on vasopressors or receiving respiratory support captures a patient's speed of
recovery. Mortality rate is a key secondary endpoint for the trial.

Specific Aims

1. To demonstrate the efficacy of combination therapy using vitamin C, thiamine and
corticosteroids to reduce the duration of cardiovascular and respiratory organ
dysfunction in critically ill patients with sepsis.

2. To demonstrate the efficacy of combination therapy using vitamin C, thiamine and
corticosteroids to reduce 30-day mortality in critically ill patients with sepsis.

Explicit subject consent for participation in long term telephone follow-up will be sought
for all patients at all sites. Participation in long term outcome assessments is not required
for participation in other aspects of the VICTAS study, i.e., patients may individually opt
out of this portion of the study. In these participants a diverse array of neurocognitive
outcomes will be assessed approximately 6 months after patient discharge. Evaluations will be
done using a specially-designed battery of tests that evaluates key aspects of functioning
and behavior and will be administered via phone by the Vanderbilt Long-Term Outcomes team,
which will serve as the coordinating center for these follow-up assessments. The battery,
which takes about 40 minutes to complete, will assess cognition, mental health, quality of
life, and employment - all of which have been shown to be adversely affected in between one
third and two thirds of survivors of sepsis.

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
We found this trial at
27
sites
Denver, Colorado 80291
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3550 Jerome Avenue
Bronx, New York 10467
(718) 920-4321
Montefiore Medical Center As the academic medical center and University Hospital for Albert Einstein College...
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Bronx, NY
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9500 Euclid Avenue
Cleveland, Ohio 44106
216.444.2200
Principal Investigator: Robert Duncan Hite, MD
Cleveland Clinic Cleveland Clinic is committed to principles as presented in the United Nations Global...
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Cleveland, OH
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1211 Medical Center Dr
Nashville, Tennessee 37232
(615) 322-5000
Principal Investigator: Wesley Self, MD, MPH
Vanderbilt Univ Med Ctr Vanderbilt University Medical Center (VUMC) is a comprehensive healthcare facility dedicated...
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Norfolk, Virginia 23507
Principal Investigator: Michael H Hooper, MD, MSc
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Norfolk, VA
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2619 E. Pierce St.
Phoenix, Arizona 85008
602-344-5951
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201 Presidents Circle
Salt Lake City, Utah 84108
801) 581-7200
Principal Investigator: Estelle Harris, MD
University of Utah Research is a major component in the life of the U benefiting...
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Salt Lake City, UT
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1364 Clifton Rd NE
Atlanta, Georgia 30322
(404) 712-2000
Principal Investigator: Katherine Nugent, MD
Emory University Hospital As the largest health care system in Georgia and the only health...
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Atlanta, GA
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80 Jesse Hill Jr Dr SE
Atlanta, Georgia 30303
(404) 616-1000
Principal Investigator: Carmen Polito, MD
Grady Memorial Hospital Grady is an internationally recognized teaching hospital staffed exclusively by doctors from...
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Atlanta, Georgia 30342
Principal Investigator: Larry Busse, MD
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1800 Orleans St.
Baltimore, Maryland 21287
410-955-5000
Principal Investigator: Jeremiah Hinson, MD, PhD
Johns Hopkins Hospital Patients are the focus of everything we do at The Johns Hopkins...
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Baltimore, Maryland 21224
Principal Investigator: David Hager, MD, PhD
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171 Ashley Avenue
Charleston, South Carolina 29425
843-792-1414
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
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Denver, Colorado 80204
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Detroit, Michigan 48202
Principal Investigator: Emanuel Rivers, MD
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Detroit, MI
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Jacksonville, Florida 32209
Principal Investigator: Faheem Guirgis, MD
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Minneapolis, Minnesota 55414
Principal Investigator: Michael Puskarich, MD, MS
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5121 S Cottonwood St
Murray, Utah 84157
(801) 507-7000
Principal Investigator: Samuel Brown, MD
Intermountain Medical Center Intermountain Medical Center is one of the most technologically advanced and patient-friendly...
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20 York St, N20 York St,
New Haven, Connecticut 06520
(203) 688-4242
Yale-New Haven Hospital Relying on the skill and expertise of more than 4,500 university and...
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New Orleans, Louisiana 70112
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Emile St
Omaha, Nebraska 68198
(402) 559-4000
Principal Investigator: Aaron Barksdale, MD
Univ of Nebraska Med Ctr A vital enterprise in the nation’s heartland, the University of...
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1801 N Broad St
Philadelphia, Pennsylvania 19122
(215) 204-7000
Principal Investigator: Nina Gentile, MD
Temple University Temple University is many things to many people. A place to pursue life's...
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Portland, Oregon 97227
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Richmond, Virginia 23298
(804) 828-0100
Principal Investigator: Berry Fowler, MD
Virginia Commonwealth University Since our founding as a medical school in 1838, Virginia Commonwealth University...
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Richmond, Virginia 85008
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Rochester, Minnesota 55905
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450 Serra Mall
Stanford, California 94305
(650) 723-2300
Principal Investigator: James Quinn, MD
Stanford University Stanford University, located between San Francisco and San Jose in the heart of...
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