Vitamin C and Septic Shock

Phase 2

Completed

Conditions: Septic Shock
Sepsis

Interventions: Drug: Placebo
Drug: Vitamin C

Registration Number: NCT03338569

Lead Sponsor: University of Minnesota

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 125

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo designed to mimic intervention
Intervention	Vitamin C	6000 mg per day Vitamin C supplement

Primary Outcome Measures

Name	Time	Method
Number of Participants With ICU Mortality	28 days	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	28 days	Outcome is reported as the number of participants who have expired at 28 days post intervention

Secondary Outcome Measures

Name	Time	Method
Duration of ICU Stay Post Intervention Administration	28 days	Outcome is reported as the duration (in days) that participants require care in the intensive care unit (ICU) post intervention administration
Duration of Vasopressor Therapy	28 days	Outcome is reported as the duration in hours of vasopressor therapy post intervention administration
Change in Serum Creatinine	Baseline and 4 days	Outcome is report as the change in serum creatinine between baseline and 4 days following treatment. Outcome is reported in units of mg/dl.
Rate of Lactate Clearance Post Intervention Administration	24, 48, 72, and 96 hours post intervention	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.
Change in Sequential Organ Failure Assessment (SOFA) Score	Baseline and 4 days	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	Baseline and 4 days	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.
Rate of Procalcitonin Clearance Post Intervention Administration	4 days
Time to Lactate Clearance Post Intervention Administration	28 days
Number of Participants With Need for Renal Replacement Therapy	4 days	Outcome is reported as the number of participants who require renal replacement therapy
Total Intravenous Fluid Administered	24 hours	Outcome is reported as the total volume of intravenous fluid (in liters) administered to participants during 24 hours following the initiation of study treatment.