High Dose Intravenous Ascorbic Acid in Severe Sepsis
Condition: Sepsis
MeSH terms: Sepsis; Toxemia
Intervention: Ascorbic Acid; Normal Saline
Intervention MeSH terms: Ascorbic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Despite an organized treatment approach outlined in expert-consensus guidelines for sepsis
      with fluid resuscitation to treat hypovolemia, antibiotics to target the infectious insult,
      and vasopressors for hypotension, mortality rates for sepsis remain high and the incidence
      continues to rise, making sepsis the most expensive inpatient disease.

        1. Recent research has described the therapeutic benefits associated with ascorbic acid
           treatment for sepsis.

        2. Researchers objectives are to perform a randomized-controlled clinical trial
           investigating the ability of ascorbic acid(vitamin C) administration to decrease organ
           dysfunction in severe sepsis. The widespread occurrence of microvascular dysfunction in
           sepsis leading to tissue hypoxia, mitochondrial dysfunction, and adenosine triphosphate
           (ATP) depletion, gives rise to organ failure.

        3. Patients with organ failure and sepsis (severe sepsis) are at a higher risk of death
           than patients with organ failure alone. Critically ill patients may have an increased
           requirement for ascorbic acid in sepsis and these patients frequently have levels below
           normal. Ascorbic acid administration, has been shown to correlate inversely with organ
           failure (human literature) and directly with survival (animal studies).

      4,5 Intravenous ascorbic acid therapy decreases organ failure by providing a protective
      effect on several microvascular functions including improving capillary blood flow,
      decreasing microvascular permeability, and improving arteriolar responsiveness to
      vasoconstrictors. Defining the utility of novel agents to augment researchers care for severe
      sepsis is an important task as investigators continue the institutional focus on sepsis care.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients with:

          1. A suspected or confirmed infection with an order for intravenous antibiotics or
             antivirals

          2. The presence of acute sepsis-induced organ dysfunction

        Definition of organ dysfunction:

          1. Arterial hypoxemia [PaO2 /FiO2 < 300]

          2. Hypotension [systolic blood pressure (SBP) < 90 mmHg or SBP decrease > 40 mmHg]

          3. Lactic acidosis [lactate > 2.5 mmol/L]

          4. Acute kidney injury [creatinine >2.0 or urine output < 0.5 ml/kg/hr for >2 hours
             despite fluid resuscitation]

          5. Thrombocytopenia [platelet count < 100,000]

          6. Acute coagulopathy [international normalized ratio (INR) > 1.5]

          7. Hepatic failure [bilirubin > 2 mg/dL].

          8. Predisposition, Infection, Response, and Organ Failure (PIRO) score ≥ 10

        Exclusion Criteria:

          1. Age < 18 years

          2. Pregnancy or breastfeeding

          3. Requirement for immediate surgery within the treatment protocol timeframe

          4. Inability to obtain written informed consent from subject or surrogate

          5. Patient to receive comfort measures only