Clinical trial NCT03338569: Vitamin C and Septic Shock
Official title: Evaluating Vitamin C in Septic Shock: A Randomized Double Blind Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Septic Shock
Sepsis
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2017-11-09
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With ICU Mortality
timeFrame: 28 days
measure: All Cause Mortality at 28 Days
timeFrame: 28 days
Secondary outcomes:
measure: Duration of Vasopressor Therapy
timeFrame: 28 days
measure: Duration of ICU Stay Post Intervention Administration
timeFrame: 28 days
measure: Time to Lactate Clearance Post Intervention Administration
timeFrame: 28 days
measure: Rate of Lactate Clearance Post Intervention Administration
timeFrame: 24, 48, 72, and 96 hours post intervention
measure: Rate of Procalcitonin Clearance Post Intervention Administration
timeFrame: 4 days
measure: Number of Participants With Need for Renal Replacement Therapy
timeFrame: 4 days
measure: Change in Serum Creatinine
timeFrame: Baseline and 4 days
measure: Change in Sequential Organ Failure Assessment (SOFA) Score
timeFrame: Baseline and 4 days
measure: Change in Acute Physiology and Chronic Health Evaluation (APACHE) Scores
timeFrame: Baseline and 4 days
measure: Total Intravenous Fluid Administered
timeFrame: 24 hours
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
Study officials:
References:
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.