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Ascorbic Acid (Vitamin C) Infusion in Human Sepsis

Primary Purpose

Sepsis, Septic Shock, Hypotension

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Ascorbic Acid

Placebo

About this trial

This is an interventional treatment trial for Sepsis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
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.
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.
Informed Consent: Ability to obtain informed consent within 48 hours.

Exclusion Criteria:

Demographic Characteristics: Children (age < 18 years), pregnant women, prisoners, and other wards of the state are excluded from participation in this study.
Informed Consent: Inability to obtain informed consent within 48 hours.
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.
Non-English Speaking Patients: Patients who are non english speaking will not be accessed to this study.

Sites / Locations

Virginia Commonwealth University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Placebo Comparator

Arm Label

High Dose Ascorbic Acid

Low Dose Ascorbic Acid

Placebo

Arm Description

Subject receives a high dose of infused Vitamin C

Subject receives a low dose of infused Vitamin C

Subject receives an infusion of saline

Outcomes

Primary Outcome Measures

Number of Patients Who Experienced Ascorbic Acid Infusion Related Arterial Hypotension, Vomiting, or Tachycardia in Septic Patients

There were no instances of arterial hypotension, vomiting, or tachycardia within the study population related to the study drug

Secondary Outcome Measures

Intensive Care Unit Length of Stay

Duration of Mechanical Ventilation

Ventilator-free Days

Length of Time on Vasopressor Medication

Multiple Organ Dysfunction Score

Plasma Cytokine/Chemokine Levels

Full Information

NCT ID

NCT01434121

First Posted

August 9, 2011

Last Updated

January 8, 2018

Sponsor

Virginia Commonwealth University

1. Study Identification

Unique Protocol Identification Number

NCT01434121

Brief Title

Ascorbic Acid (Vitamin C) Infusion in Human Sepsis

Official Title

Ascorbic Acid (Vitamin C) Infusion in Human Sepsis

Study Type

Interventional

2. Study Status

Record Verification Date

January 2018

Overall Recruitment Status

Completed

Study Start Date

May 2010 (undefined)

Primary Completion Date

September 2012 (Actual)

Study Completion Date

September 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Virginia Commonwealth University

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sepsis, Septic Shock, Hypotension, Acute Lung Injury

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

High Dose Ascorbic Acid

Arm Type

Active Comparator

Arm Description

Subject receives a high dose of infused Vitamin C

Arm Title

Low Dose Ascorbic Acid

Arm Type

Active Comparator

Arm Description

Subject receives a low dose of infused Vitamin C

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Subject receives an infusion of saline

Intervention Type

Drug

Intervention Name(s)

Ascorbic Acid

Other Intervention Name(s)

Vitamin C

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Number of Patients Who Experienced Ascorbic Acid Infusion Related Arterial Hypotension, Vomiting, or Tachycardia in Septic Patients

Description

There were no instances of arterial hypotension, vomiting, or tachycardia within the study population related to the study drug

Time Frame

during time of infusion- 96 hours from time of enrollment

Secondary Outcome Measure Information:

Title

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

Title

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

Title

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

Title

Length of Time on Vasopressor Medication

Time Frame

during time of infusion - 96 hours from time of enrollment

Title

Multiple Organ Dysfunction Score

Time Frame

during time of infusion - 96 hours from time of enrollment

Title

Plasma Cytokine/Chemokine Levels

Time Frame

during time of infusions - 96 hours from time of enrollment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 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. 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. Informed Consent: Ability to obtain informed consent within 48 hours. Exclusion Criteria: Demographic Characteristics: Children (age < 18 years), pregnant women, prisoners, and other wards of the state are excluded from participation in this study. Informed Consent: Inability to obtain informed consent within 48 hours. 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. Non-English Speaking Patients: Patients who are non english speaking will not be accessed to this study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alpha Fowler, MD

Organizational Affiliation

Virginia Commonwealth University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Virginia Commonwealth University

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23298

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24484547

Citation

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.

Results Reference

derived

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Ascorbic Acid (Vitamin C) Infusion in Human Sepsis

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