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

• Sponsor: Emory University
• Collaborator: The Marcus Foundation
• Information provided by (Responsible Party): Jonathan Sevransky, Emory University

Study Description

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

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Study Design

• Study Type: Interventional (Clinical Trial)
• 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

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

• 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

Contacts and Locations

Contacts

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

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Sponsors and Collaborators

Emory University

The Marcus Foundation

Investigators

• Principal Investigator: Jonathan Sevransky, MD, MHS; Emory University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hager DN, Hooper MH, Bernard GR, Busse LW, Ely EW, Fowler AA, Gaieski DF, Hall A, Hinson JS, Jackson JC, Kelen GD, Levine M, Lindsell CJ, Malone RE, McGlothlin A, Rothman RE, Viele K, Wright DW, Sevransky JE, Martin GS. The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) Protocol: a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial. Trials. 2019 Apr 5;20(1):197. doi: 10.1186/s13063-019-3254-2.

• 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
• Last Update Posted: June 12, 2019
• Last Verified: June 2019

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; 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