HAT for the Treatment of Sepsis Associated With NASTI

Ascension Via Christi Hospitals Wichita, Inc.

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Necrotizing Soft Tissue Infection; Sepsis

Treatments: Drug: Placebo; Drug: HAT

Study type: Interventional

Funder types: Other

Identifiers

NCT05157360

KUVC1814

Details and patient eligibility

About

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

Full description

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

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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10 participants in 2 patient groups, including a placebo group

Treatment Arm

Experimental group

Description:

Patients will be enrolled within 24 hours of diagnosis of sepsis related to a necrotizing soft-tissue infections (NSTI). HAT will be initiated within 4 hours of enrollment (thus treatment with HAT can occur no later than 28 hours from diagnosis). Per Dr. Marik's original study, HAT consists of: 1. 1.5 g vitamin C every 6 hours for 4 days or until ICU discharge 2. 50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days) 3. 200 mg thiamine every 12 hours for 4 days or until ICU discharge In our study, due to the prolonged ICU course typical of most patients with NSTIs, it is not felt feasible to continue indefinitely "until ICU discharge." Thus, treatment will be continued for 4 to 7 days plus a 3 day taper (respectively) as above, with no plan for a longer duration of treatment.

Treatment:

Drug: HAT

Control Arm

Placebo Comparator group

Description:

The control arm will receive the same standard ICU care for NSTI but will not receive HAT. They will receive a placebo consisting of normal saline, indistinguishable to the treatment team (blinded) but known to the pharmacy team (unblinded to treatment and placebo groups). This is so that if the treatment team elects to give stress dose steroids, they can be administered without breaking protocol (i.e. if the patient is getting HAT, it includes steroids, so if the treating team wanted to start hydrocortisone - because they didn't know if the patient was on HAT or placebo and felt steroids were indicated - the pharmacist could ensure the patient was on steroids one way or another without unblinding the providers).

Treatment:

Drug: Placebo