HAT for the Treatment of Sepsis Associated With NASTI

Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Sepsis Associated With Acute Necrotizing Soft Tissue Infections, The NASTI HAT Trial

Evaluate the impact of HAT therapy versus placebo in the treatment of patients with an acute NSTI and sepsis.

Primary outcome:

1. Hospital survival

Secondary outcomes:

1. Duration of vasopressor therapy

2. Requirement for renal replacement therapy in patients with Acute Kidney Injury (AKI)

3. ICU length of stay (LOS)

4. Change in serum procalcitonin (PCT) over first 72 hours

5. Change in SOFA score over first 72 hours (measured as SOFA score daily for four days, with day one being admission, then 3 days after, totaling 4 days of treatment with HAT)

6. Procalcitonin clearance (formula = initial PCT - 72 hour PCT divided by initial PCT x 100)

7. Number of wound related surgeries

8. Wound status at time of hospital discharge:

   1. Open
   2. Closed

Inclusion Criteria:

1. Necrotizing soft tissue infection by clinical diagnosis and requiring surgical treatment.
2. Sepsis by clinical diagnosis and/or by Sepsis-3 criteria15, with source attributed to the wound.
3. Anticipated or confirmed intensive care unit

Exclusion Criteria: (Adapted from Sevransky et. al's VICTAS protocol)

1. Age < 18 years of age
2. Weight < 40 kg
3. Prior enrollment in this study or current enrollment in another study of any kind
4. Surgical findings, pathology/histology findings, or other findings determined to be inconsistent with an infectious acute NSTI such that the clinical diagnosis is no longer that of a NSTI
5. Sepsis deemed unlikely
6. Limitations of care during enrollment [defined as refusal of cardiovascular and respiratory support modes described in inclusion criteria, including "do not intubate" (DNI) status and comfort care]
7. Known allergy or known contraindication to vitamin C, thiamine, or corticosteroids [including previous history or active diagnosis of primary hyperoxaluria and/or oxalate nephropathy, or known/suspected ethylene glycol ingestion, or known glucose-6-phosphate dehydrogenase (G6PD) deficiency]
8. Use of vitamin C at a dose of >1g/day (IV or oral) within the 24 hours preceding first episode of qualifying organ dysfunction during a given Emergency Department or Intensive Care Unit admission
9. Chronic disease/illness that, in the opinion of the site investigator, have an expected lifespan of < 30 days unrelated to current sepsis diagnosis (e.g., stage IV malignancy, neurodegenerative disease, etc.)
10. Kidney Stone(s) of any kind
11. History of Oxalate Kidney Stone(s)
12. Pregnancy or known active breastfeeding
13. Prisoner or Incarceration
14. Inability or unwillingness of subject or legal surrogate/representative to give written informed consent