Vitamin C and Septic Shock

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.

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