Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in Sepsis.
Condition: Sepsis, Severe; Septic Shock
MeSH terms: Sepsis; Toxemia
Intervention: Ascorbic Acid; Thiamine; Hydrocortisone; Sodium Chloride 0.9%
Intervention description: Ascorbic Acid 1.5g IV piggyback every 6 hours for 4 days (or discharge from ICU if prior to 4 days).; Thiamine 200mg IV piggyback every 12 hours for 4 days (or discharge from ICU if prior to 4 days).; Hydrocortisone 50mg IV push every 6 hours for 4 days (or discharge from ICU if prior to 4 days).; Placebo "Ascorbic Acid" 100mL IV piggyback every 6 hours, Placebo "Thiamine" 50mL IV piggyback every 12 hours, and Placebo "Hydrocortisone" IV push every 6 hours for 4 days (or discharge from ICU if prior to 4 days).
Intervention MeSH terms: Ascorbic Acid; Thiamine; Hydrocortisone; Hydrocortisone hemisuccinate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a double-blind placebo controlled study. Only the dispensing pharmacist will be aware of the treatment allocation. Patients will be randomized to receive either vitamin C/hydrocortisone/thiamine or triple placebo using a random number table provided to the dispensing pharmacists. Each patient will be allocated a unique subject ID which will be linked to the randomization sequence. Only the dispensing pharmacists will have a record of the subject ID and randomization sequence.
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Patients will be randomized to receive either vitamin C/hydrocortisone/thiamine or triple placebo using a random number table provided to the dispensing pharmacists. Each patient will be allocated a unique subject ID which will be linked to the randomization sequence. Only the dispensing pharmacists will have a record of the subject ID and randomization sequence.
Enrollment: 140.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study has been created to compare the addition of intravenous (IV) vitamin C, thiamine,
      and hydrocortisone to the usual standard of care of sepsis and septic shock. Sepsis is a
      possibly life-threatening condition in which a patient may have organ dysfunction due to an
      infection. Septic shock is defined as low blood pressure and organ dysfunction that do not
      improve after administering IV fluids. Standard of care for sepsis and septic shock include
      early administration of IV antibiotics, IV fluids, and vasopressors if need be to provide
      oxygen to vital organs.

      A large amount of experimental data has shown that vitamin C and corticosteroids decrease the
      release of inflammatory substances which may lead to organ failure seen in sepsis. Vitamin C
      and corticosteroids also improve blood flow to vital organs and increase the body's ability
      to respond well to vasopressor medications used in septic shock. Low blood levels of both
      thiamine and vitamin C are common in sepsis. The study will be placebo controlled, meaning
      one group will receive vitamin C, thiamine, and hydrocortisone, and the other will receive an
      inactive substance ("placebo"). The goal of the study is to compare the effects of receiving
      vitamin C, thiamine, and hydrocortisone (along with the standard sepsis care) versus placebo
      and standard sepsis care.
    

Eligibility criteria:

        Inclusion Criteria:

        i. Diagnosis of sepsis or septic shock within 12 hours of admission to the ICU ii. Informed
        consent as dictated by IRB and local practice. iii. Compliance with the 3 hour sepsis
        bundle

          -  30ml/kg of intravenous crystalloid fluid (e.g.: sodium chloride 0.9%) for lactic acid
             >4 and/or systolic blood pressure <90mmHg / mean arterial pressure <65mmHg

          -  Lactic acid level drawn

          -  Broad spectrum antibiotics given after obtaining blood cultures

        Exclusion Criteria:

        i. Age < 18 years ii. Pregnant iii. DNR/DNI with limitations of care on admission iv.
        Patients with terminal end stage disease (i.e. stage IV cancer, end stage heart failure)
        that are unlikely to survive to hospital discharge v. Patients with a primary admitting
        diagnosis of an acute cerebral vascular event, acute coronary syndrome, active
        gastrointestinal bleeding, burn or trauma [64-66] vi. Requirement for immediate surgery
        [64-66] vii. Patients with HIV and a CD4 < 50 mm2 [64-66] viii. Patients with known
        glucose-6 phosphate dehydrogenase (G-6PD) deficiency.[39] ix. Patients with sepsis/septic
        shock transferred from another hospital x. Patients with features of sepsis/septic shock >
        24 hours after admission