Ascorbic Acid and Thiamine Effect in Septic Shock
Condition: Septic Shock; Sepsis
MeSH terms: Shock, Septic; Shock
Study type: Interventional
Phase: Phase 2

Summary: 
      The aim of this study is to evaluate the efficacy of early metabolic resuscitation with
      combination therapy using vitamin C and thiamine in improving organ function and survival in
      patients with septic shock.
    

Detailed description: 
      Sepsis is a complex disease involving life-threatening organ dysfunction caused by a
      dysregulated host response to infection and is still associated with unacceptably high
      mortality. Sepsis management should be undertaken as a medical emergency and focused on
      timely intervention, including early identification and treatment of infection through
      appropriate antimicrobial therapy and source control when applicable as well as reversing
      hemodynamic instability through fluid resuscitation and vasopressor use if necessary. Despite
      these supportive therapies, morbidity and mortality have remained high, suggesting the need
      for adjuvant therapies for inflammatory and oxidative stress in patients with sepsis;
      however, no agents have been proven to definitely improve survival.

      Vitamin C plays a role in mediating inflammation through antioxidant activities and is also
      important as a cofactor/co-substrate for the synthesis of endogenous adrenaline, cortisol,
      and vasopressin. Recently, several clinical trials have reported the positive effects of
      vitamin C on outcomes in sepsis or septic shock. During sepsis, vitamin C prevents
      neutrophil-induced lipid oxidation and protects against the loss of the endothelial barrier.
      Early intravenous supplementation is therefore needed to limit loss of microcirculation and
      oxidation of lipids. Thiamine is also a key cofactor for glucose metabolism, the generation
      of ATP (adenosine triphosphate), and the production of NADPH. Considering acute consumption
      in the hypermetabolic state, thiamine supplementation might be a reasonable therapeutic
      adjunct for patients with sepsis and was added to reduce the risk of renal oxalate
      crystallization. These findings led to a recent before-and-after study showing that treatment
      of sepsis with a combination of vitamin C, hydrocortisone, and thiamine prevented organ
      dysfunction and reduced the mortality rate.

      The aim of this study is to evaluate the efficacy of early metabolic resuscitation with
      combination therapy using vitamin C and thiamine in improving organ function and survival in
      patients with septic shock.
    

Intervention name(s): Combination therapy of vitamin C and thiamine; Normal saline solution
Intervention type(s): Drug; Drug
Intervention description(s): Vitamin C (50 mg/kg up to 3 g, every 12 hours) and thiamine (200 mg every 12 hours) intravenously administered mixed in 50 mL solution bags of normal saline for 2 days; Normal saline solution in a volume to match the treatment components administered mixed in 50 mL solution bags of normal saline for 2 days
Other intervention name(s): Ascorbic Acid Injection; Thiamine Injection; 0.9% NaCl
Intervention MeSH terms: Ascorbic Acid; Thiamine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Multi-center, Double-blinded, Randomized, Controlled Study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Septic shock; Sepsis; Vitamin C; Thiamine