Vitamin C, Thiamine, and Steroids in Sepsis
Condition: Sepsis
MeSH terms: Sepsis; Toxemia
Intervention: Vitamin C; Thiamine; Hydrocortisone; Vitamin C Placebo; Thiamine Placebo; Hydrocortisone Placebo
Intervention description: Intravenous vitamin C (1.5 grams every 6 hours) will be administered for 4 days or until ICU discharge.; Intravenous thiamine (100 mg every 6 hours) will be administered for 4 days or until ICU discharge.; Intravenous hydrocortisone (50 mg every 6 hours) will be administered for 4 days or until ICU discharge.; A placebo to match intravenous vitamin C (1.5 grams every 6 hours) will be administered for 4 days or until ICU discharge.; A placebo to match intravenous thiamine (100 mg every 6 hours) will be administered for 4 days or until ICU discharge.; 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.
Intervention MeSH terms: Vitamins; Ascorbic Acid; Thiamine; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 501.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Vitamin C; Thiamine; Corticosteroid

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Suspected or confirmed infection as evidenced by ordering of blood cultures and
             administration of at least one antimicrobial agent

          -  Anticipated or confirmed intensive care unit (ICU) admission

          -  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
                  ≥ 40 liter per minute (LPM) flow and FiO2 ≥ 0.40

        Exclusion Criteria:

          -  Weight < 40 kilograms (kg)

          -  Prior enrollment in this study

          -  Qualifying organ dysfunction no longer present at the time subject would be randomized

          -  Cardiovascular or respiratory organ failure caused by an illness other than sepsis

          -  First episode of qualifying organ dysfunction during the current emergency department
             (ED) or ICU admission occurred > 24 hours before the subject could be randomized

          -  Limitations of care (defined as refusal of cardiovascular and respiratory support
             modes) 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 known/suspected ethylene glycol ingestion, or known
             glucose-6-phosphate dehydrogenase (G6PD) deficiency)

          -  Use of vitamin C at a dose of > 1 gram daily within the 24 hours preceding first
             episode of qualifying organ dysfunction during a given ED or ICU admission

          -  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 research study

          -  Inability or unwillingness of subject or legal surrogate/representative to give
             written informed consent