Vitamin C and Septic Shock

Evaluating Vitamin C in Septic Shock: A Randomized Double Blind Placebo Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock
• Intervention / Treatment: Drug: Placebo; Drug: Vitamin C

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.

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
SHAM_COMPARATOR: Placebo; Placebo designed to mimic intervention	Drug: Placebo; Placebo designed to mimic intervention
ACTIVE_COMPARATOR: Intervention; 6000 mg per day Vitamin C supplement	Drug: Vitamin C; Continuous infusion of vitamin C; Other Names: ascorbic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	28 days
All Cause Mortality at 28 Days	Outcome is reported as the number of participants who have expired at 28 days post intervention	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Vasopressor Therapy	Outcome is reported as the duration in hours of vasopressor therapy post intervention administration	28 days
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	28 days
Time to Lactate Clearance Post Intervention Administration		28 days
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.	24, 48, 72, and 96 hours post intervention
Rate of Procalcitonin Clearance Post Intervention Administration		4 days
Number of Participants With Need for Renal Replacement Therapy	Outcome is reported as the number of participants who require renal replacement therapy	4 days
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.	Baseline and 4 days
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.	Baseline and 4 days
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.	Baseline and 4 days
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.	24 hours

Collaborators and Investigators

• Sponsor: University of Minnesota

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 20, 2017
• Primary Completion (ACTUAL): June 30, 2020
• Study Completion (ACTUAL): August 10, 2020

Study Registration Dates

• First Submitted: October 31, 2017
• First Submitted That Met QC Criteria: November 8, 2017
• First Posted (ACTUAL): November 9, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 14, 2021
• Last Update Submitted That Met QC Criteria: July 13, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid
• Other Study ID Numbers: STUDY00000625

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• 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