Ascorbic Acid (Vitamin C) Infusion in Human Sepsis

• ClinicalTrials.gov Identifier: NCT01434121
• Recruitment Status: Completed
• First Posted: September 14, 2011
• Results First Posted: July 1, 2014
• Last Update Posted: February 1, 2018
• Sponsor: Virginia Commonwealth University
• Information provided by (Responsible Party): Virginia Commonwealth University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Sepsis; Septic Shock; Hypotension; Acute Lung Injury	Drug: Ascorbic Acid; Drug: Placebo	Phase 1; Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Ascorbic Acid (Vitamin C) Infusion in Human Sepsis
• Study Start Date: May 2010
• Actual Primary Completion Date: September 2012
• Actual Study Completion Date: September 2012

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: High Dose Ascorbic Acid; Subject receives a high dose of infused Vitamin C	Drug: Ascorbic Acid; The infusion of either a high dose of ascorbic acid, low dose ascorbic acid, or placebo; Other Name: Vitamin C
Active Comparator: Low Dose Ascorbic Acid; Subject receives a low dose of infused Vitamin C	Drug: Ascorbic Acid; The infusion of either a high dose of ascorbic acid, low dose ascorbic acid, or placebo; Other Name: Vitamin C
Placebo Comparator: Placebo; Subject receives an infusion of saline	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Number of Patients Who Experienced Ascorbic Acid Infusion Related Arterial Hypotension, Vomiting, or Tachycardia in Septic Patients [ Time Frame: during time of infusion- 96 hours from time of enrollment ]
   There were no instances of arterial hypotension, vomiting, or tachycardia within the study population related to the study drug

Secondary Outcome Measures :

1. Intensive Care Unit Length of Stay [ Time Frame: subject will be followed until discharged from the ICU, has deceased, or study duration has reached 28 days from time of enrollment, whichever is first ]
2. Duration of Mechanical Ventilation [ Time Frame: subject will be followed until mechanical ventilation has been discontinued, the subject has deceased, or study duration has reached 28 days from time of enrollment, whichever is first ]
3. Ventilator-free Days [ Time Frame: subject will be followed until discharged from the hospital, has deceased, or study duration has reached 28 days from time of enrollment, whichever is first ]
4. Length of Time on Vasopressor Medication [ Time Frame: during time of infusion - 96 hours from time of enrollment ]
5. Multiple Organ Dysfunction Score [ Time Frame: during time of infusion - 96 hours from time of enrollment ]
6. Plasma Cytokine/Chemokine Levels [ Time Frame: during time of infusions - 96 hours from time of enrollment ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Locations

United States, Virginia

Virginia Commonwealth University

Richmond, Virginia, United States, 23298

Sponsors and Collaborators

Virginia Commonwealth University

Investigators

• Principal Investigator: Alpha Fowler, MD; Virginia Commonwealth University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fowler AA 3rd, Syed AA, Knowlson S, Sculthorpe R, Farthing D, DeWilde C, Farthing CA, Larus TL, Martin E, Brophy DF, Gupta S; Medical Respiratory Intensive Care Unit Nursing, Fisher BJ, Natarajan R. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014 Jan 31;12:32. doi: 10.1186/1479-5876-12-32.

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT01434121
• Other Study ID Numbers: HM12903
• First Posted: September 14, 2011
• Results First Posted: July 1, 2014
• Last Update Posted: February 1, 2018
• Last Verified: January 2018

Additional relevant MeSH terms:

Sepsis; Toxemia; Lung Injury; Acute Lung Injury; Hypotension; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Thoracic Injuries; Wounds and Injuries; Ascorbic Acid; Vitamins; Micronutrients; Physiological Effects of Drugs; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents