Ascorbic Acid (Vitamin C) Infusion in Human Sepsis
Information source: Virginia Commonwealth University
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Sepsis; Septic Shock; Hypotension; Acute Lung Injury
Intervention: Ascorbic Acid (Drug); Placebo (Drug)
Phase: Phase 1/Phase 2
Sponsored by: Virginia Commonwealth University
Official(s) and/or principal investigator(s):
Alpha Fowler, MD, Principal Investigator, Affiliation: Virginia Commonwealth University
The major goal of this project is to determine whether intravenously infused ascorbic acid
is safe for use as a viable therapeutic strategy in adult humans with sepsis.
Official title: Ascorbic Acid (Vitamin C) Infusion in Human Sepsis
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Number of Patients Who Experienced Ascorbic Acid Infusion Related Arterial Hypotension, Vomiting, or Tachycardia in Septic Patients
Intensive Care Unit Length of Stay
Duration of Mechanical Ventilation
Length of Time on Vasopressor Medication
Multiple Organ Dysfunction Score
Plasma Cytokine/Chemokine Levels
Evolving data from experimental animals strongly suggests that ascorbic acid potently
interrupts multiple biological processes which lead to organ injury following onset of
sepsis. Data presented below suggests that ascorbic acid potently attenuates lung injury
produced by septic insults. Sepsis and septic shock secondary to bacterial and fungal blood
stream infections are a leading cause of death in critically ill patients. At present, 28
day mortality in septic patients averages 40% in the best of ICUs. In sepsis, disseminated
intravascular coagulation produces widespread systemic microvascular thrombosis that leads
to multiple organ injury (i. e., lung, liver, kidney, intestinal, cardiovascular). Despite
aggressive intravascular volume resuscitation and vasopressor support, appropriate
antibiotic administration, and expert critical care management, mortality remains high. Only
a single agent has been approved to disrupt progressive sepsis-associated microvascular
thrombosis (activated protein C, [Drodrecogin Alpha, brand name: Xigris, Lilly]). No other
non-antibiotic pharmaceutical agent is currently approved for use in sepsis. Activated
protein C (APC) continuous infusion protocol spans a 96 hour period. APC infusion produces
significant anticoagulation, and therefore the major risk from its use is hemorrhage. Thus,
recent surgery, especially neurosurgical procedures, is a major contraindication to APC use.
Finally, cost stands as an important issue for APC use. A 96 hour APC infusion in a 70 kg
patient at VCUHS costs the patient over $33,000 (source VCUHS Pharmacy Services). Use of APC
in sepsis remains controversial and has failed to achieve widespread acceptance. The goal of
the current study is to determine the safety of ascorbic acid infusion in septic humans.
Minimum age: 18 Years.
Maximum age: N/A.
1. systemic inflammatory response: fever (38°C or greater) or hypothermia (36°C or
lower), tachypnea (20 breaths/min) or need for mechanical ventilation for an acute
process, tachycardia (rate 90/min or more), white blood cell count ≥ 12,000 cells/mm3
or ≤ 4,000 cells/mm3 or more than 10% band forms.
2. Presumed or Known Site of Infection: Purulent sputum, chest radiograph with new
infiltrate, spillage of bowel contents, radiographic or physical examination evidence
of an infected collection, white blood cells in a normally sterile body fluid,
positive blood culture, evidence of infected mechanical hardware by physical,
radiographic, or ultrasonographic evidence.
3. Evidence of Dysfunction of One or More End Organs: cardiovascular dysfunction: mean
arterial pressure 60 mm Hg or less, the need for vasopressors to maintain this
pressure in the presence of adequate intravascular volume (central venous pressure 12
mmHg); respiratory failure: (arterial PO2-to-FiO2 ratio of less than 250 or less than
200 in the presence of pneumonia; renal dysfunction: Urine output ≤ 0. 5 ml/kg/hr for
2 hours in the presence of adequate intravascular volume or doubling of the serum
creatinine; hematologic dysfunction: thrombocytopenia ≤ 80,000 platelets/mm3 or 50%
decrease from baseline during the acute illness; Unexplained metabolic acidosis:
arterial pH ≤ 7. 3 and a plasma lactate level higher than 2. 5. Hepatic Dysfunction:
Acute Serum transaminase elevation greater than five times normal.
4. Informed Consent: Ability to obtain informed consent within 48 hours.
1. Demographic Characteristics: Children (age < 18 years), pregnant women, prisoners,
and other wards of the state are excluded from participation in this study.
2. Informed Consent: Inability to obtain informed consent within 48 hours.
3. Cognitive Impairment: In the absence of family or next of kin, if the investigators
feel the patient is cognitively impaired, and unable to provide informed consent, the
patient will not be accessed to the study.
4. Non-English Speaking Patients: Patients who are non english speaking will not be
accessed to this study.
Locations and Contacts
Virginia Commonwealth University, Richmond, Virginia 23298, United States
Starting date: May 2010
Last updated: May 30, 2014