Ascorbic Acid (Vitamin C) Infusion in Human Sepsis

NCT ID: NCT01434121

Last Updated: 2018-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2012-09-30

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.

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.

Conditions

Sepsis; Septic Shock; Hypotension; Acute Lung Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

High Dose Ascorbic Acid

Subject receives a high dose of infused Vitamin C

Group Type: ACTIVE_COMPARATOR

Ascorbic Acid

Intervention Type: DRUG

The infusion of either a high dose of ascorbic acid, low dose ascorbic acid, or placebo

Low Dose Ascorbic Acid

Subject receives a low dose of infused Vitamin C

Group Type: ACTIVE_COMPARATOR

Ascorbic Acid

Intervention Type: DRUG

The infusion of either a high dose of ascorbic acid, low dose ascorbic acid, or placebo

Placebo

Subject receives an infusion of saline

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Ascorbic Acid

The infusion of either a high dose of ascorbic acid, low dose ascorbic acid, or placebo

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Vitamin C

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alpha Fowler, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 24484547 (View on PubMed)

Other Identifiers

HM12903

Identifier Type: -

Identifier Source: org_study_id