Back to resultsVitamin C and Septic Shock
Primary Purpose
Septic Shock, Sepsis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Vitamin C
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Septic Shock
Eligibility Criteria
Inclusion Criteria:
• Capability to provide written consent from participant or legally authorized representative (LAR) if the participant is unable or incapacitated due to severity of illness.
- Age ≥ 18 years
Septic shock as pragmatically defined as:
o Order for intravenous antimicrobials with either procalcitonin > 2 mg/dL within 24 hours of enrollment OR other clinical suspicion of infection or confirmed infection AND
- Hypotension requiring vasopressor therapy, despite fluid resuscitation of at least 30 cc/kg AND
- Lactate > 2 mmol/L 24 hr prior to enrollment AND
Presence of sepsis defined as equal to or greater than 2 SIRS criteria and/or acute increase in qSOFA score of 2 points or more.
- SIRS criteria: 1) Temperature greater than 38° or less than 36° Celsius. 2) Heart rate greater than 90 beats per minute. 3) Respiratory rate greater than 20 breaths per minute OR arterial carbon dioxide tension less than 32 mmHg. 4) White blood cell count greater than 12,000 cell/µL, less than 4,000 cells/µL, OR band cells greater than 10% of the total white blood cell population.
- qSOFA: 1 point each is assigned for: 1) systolic blood pressure below 100, 2) respiratory rate greater than 22, and 3) mental status not at baseline.
Exclusion Criteria:
• Unable to start infusion within 24 hours of septic shock identification
- Currently pregnant or breastfeeding
- Patient to receive comfort measures only
- Cardiac Arrest
- Cardiovascular Surgery patients receiving prophylactic peri-operative antibiotics < 48 hours post-operation
- Participation in another study involving an investigational product within 30 days of the baseline visit
- Allergy to Vitamin C
- History of nephrolithiasis
- History of G6PD deficiency
- ESRD patients, transplant eligible on dialysis currently taking vitamin C supplementation
- Clinical course that treating clinician decides would preclude safe participation
Sites / Locations
- University of Minnesota Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Sham Comparator
Active Comparator
Arm Label
Placebo
Intervention
Arm Description
Placebo designed to mimic intervention
6000 mg per day Vitamin C supplement
Outcomes
Primary Outcome Measures
Number of Participants With ICU Mortality
Outcome is reported as the number of patients who expired while receiving care in the intensive care unit (ICU).
All Cause Mortality at 28 Days
Outcome is reported as the number of participants who have expired at 28 days post intervention
Secondary Outcome Measures
Duration of Vasopressor Therapy
Outcome is reported as the duration in hours of vasopressor therapy post intervention administration
Duration of ICU Stay Post Intervention Administration
Outcome is reported as the duration (in days) that participants require care in the intensive care unit (ICU) post intervention administration
Time to Lactate Clearance Post Intervention Administration
Rate of Lactate Clearance Post Intervention Administration
Outcome is reported as the number of participants who clear lactate from the bloodstream at 24, 48, 72, and 96 hours post intervention. Clearance is defined as a serum concentration of 2.0 mmol/l or less.
Rate of Procalcitonin Clearance Post Intervention Administration
Number of Participants With Need for Renal Replacement Therapy
Outcome is reported as the number of participants who require renal replacement therapy
Change in Serum Creatinine
Outcome is report as the change in serum creatinine between baseline and 4 days following treatment. Outcome is reported in units of mg/dl.
Change in Sequential Organ Failure Assessment (SOFA) Score
SOFA score is a mortality prediction score that is based on the degree of dysfunction of 6 organ systems. Total scores range from 0 to 24, with higher scores indicating higher likely mortality.
Change in Acute Physiology and Chronic Health Evaluation (APACHE) Scores
APACHE score is a severity-of-disease classification system that is calculated from a patient's age and 12 routine physiological measurements. Total scores are computed based on several measurements and range from 0 to 71 with higher scores corresponding to more severe disease and a higher risk of death.
Total Intravenous Fluid Administered
Outcome is reported as the total volume of intravenous fluid (in liters) administered to participants during 24 hours following the initiation of study treatment.
Full Information
NCT ID
NCT03338569
First Posted
October 31, 2017
Last Updated
July 13, 2021
Sponsor
University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT03338569
Brief Title
Vitamin C and Septic Shock
Official Title
Evaluating Vitamin C in Septic Shock: A Randomized Double Blind Placebo Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
December 20, 2017 (Actual)
Primary Completion Date
June 30, 2020 (Actual)
Study Completion Date
August 10, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a randomized, double-blind, placebo-controlled clinical trial to compare Vitamin C versus placebo for patients presenting to the ICU with a diagnosis of septic shock.
Detailed Description
This is a multi-site, randomized, double-blind, placebo-controlled trial comparing a regimen of moderate-dose (6000 mg per day) Vitamin C supplementation versus placebo for the treatment of patients presenting to the ICU with septic shock. Both groups will continue to receive all other standard of care measures for septic shock as clinically indicated. Groups will be enrolled and receive study drug/placebo for 4 days (96 hours) or until 24 hours post-last pressor dose, whichever is sooner.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Septic Shock, Sepsis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
125 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Sham Comparator
Arm Description
Placebo designed to mimic intervention
Arm Title
Intervention
Arm Type
Active Comparator
Arm Description
6000 mg per day Vitamin C supplement
Intervention Type
Drug
Intervention Name(s)
Vitamin C
Other Intervention Name(s)
ascorbic acid
Intervention Description
Continuous infusion of vitamin C
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo designed to mimic intervention
Primary Outcome Measure Information:
Title
Number of Participants With ICU Mortality
Description
Outcome is reported as the number of patients who expired while receiving care in the intensive care unit (ICU).
Time Frame
28 days
Title
All Cause Mortality at 28 Days
Description
Outcome is reported as the number of participants who have expired at 28 days post intervention
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Duration of Vasopressor Therapy
Description
Outcome is reported as the duration in hours of vasopressor therapy post intervention administration
Time Frame
28 days
Title
Duration of ICU Stay Post Intervention Administration
Description
Outcome is reported as the duration (in days) that participants require care in the intensive care unit (ICU) post intervention administration
Time Frame
28 days
Title
Time to Lactate Clearance Post Intervention Administration
Time Frame
28 days
Title
Rate of Lactate Clearance Post Intervention Administration
Description
Outcome is reported as the number of participants who clear lactate from the bloodstream at 24, 48, 72, and 96 hours post intervention. Clearance is defined as a serum concentration of 2.0 mmol/l or less.
Time Frame
24, 48, 72, and 96 hours post intervention
Title
Rate of Procalcitonin Clearance Post Intervention Administration
Time Frame
4 days
Title
Number of Participants With Need for Renal Replacement Therapy
Description
Outcome is reported as the number of participants who require renal replacement therapy
Time Frame
4 days
Title
Change in Serum Creatinine
Description
Outcome is report as the change in serum creatinine between baseline and 4 days following treatment. Outcome is reported in units of mg/dl.
Time Frame
Baseline and 4 days
Title
Change in Sequential Organ Failure Assessment (SOFA) Score
Description
SOFA score is a mortality prediction score that is based on the degree of dysfunction of 6 organ systems. Total scores range from 0 to 24, with higher scores indicating higher likely mortality.
Time Frame
Baseline and 4 days
Title
Change in Acute Physiology and Chronic Health Evaluation (APACHE) Scores
Description
APACHE score is a severity-of-disease classification system that is calculated from a patient's age and 12 routine physiological measurements. Total scores are computed based on several measurements and range from 0 to 71 with higher scores corresponding to more severe disease and a higher risk of death.
Time Frame
Baseline and 4 days
Title
Total Intravenous Fluid Administered
Description
Outcome is reported as the total volume of intravenous fluid (in liters) administered to participants during 24 hours following the initiation of study treatment.
Time Frame
24 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
• Capability to provide written consent from participant or legally authorized representative (LAR) if the participant is unable or incapacitated due to severity of illness.
Age ≥ 18 years
Septic shock as pragmatically defined as:
o Order for intravenous antimicrobials with either procalcitonin > 2 mg/dL within 24 hours of enrollment OR other clinical suspicion of infection or confirmed infection AND
Hypotension requiring vasopressor therapy, despite fluid resuscitation of at least 30 cc/kg AND
Lactate > 2 mmol/L 24 hr prior to enrollment AND
Presence of sepsis defined as equal to or greater than 2 SIRS criteria and/or acute increase in qSOFA score of 2 points or more.
SIRS criteria: 1) Temperature greater than 38° or less than 36° Celsius. 2) Heart rate greater than 90 beats per minute. 3) Respiratory rate greater than 20 breaths per minute OR arterial carbon dioxide tension less than 32 mmHg. 4) White blood cell count greater than 12,000 cell/µL, less than 4,000 cells/µL, OR band cells greater than 10% of the total white blood cell population.
qSOFA: 1 point each is assigned for: 1) systolic blood pressure below 100, 2) respiratory rate greater than 22, and 3) mental status not at baseline.
Exclusion Criteria:
• Unable to start infusion within 24 hours of septic shock identification
Currently pregnant or breastfeeding
Patient to receive comfort measures only
Cardiac Arrest
Cardiovascular Surgery patients receiving prophylactic peri-operative antibiotics < 48 hours post-operation
Participation in another study involving an investigational product within 30 days of the baseline visit
Allergy to Vitamin C
History of nephrolithiasis
History of G6PD deficiency
ESRD patients, transplant eligible on dialysis currently taking vitamin C supplementation
Clinical course that treating clinician decides would preclude safe participation
Facility Information:
Facility Name
University of Minnesota Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34982738
Citation
Wacker DA, Burton SL, Berger JP, Hegg AJ, Heisdorffer J, Wang Q, Medcraft EJ, Reilkoff RA. Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy. Crit Care Med. 2022 May 1;50(5):e458-e467. doi: 10.1097/CCM.0000000000005427. Epub 2022 Jan 5.
Results Reference
derived
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Vitamin C and Septic Shock
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