HAT for the Treatment of Sepsis Associated With NASTI

NCT ID: NCT05157360

Last Updated: 2024-07-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-10
• Study Completion Date: 2023-05-16

Brief Summary

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

Detailed 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

Conditions

Necrotizing Soft Tissue Infection; Sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Treatment Arm

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.

Group Type: EXPERIMENTAL

HAT

Intervention Type: DRUG

hydrocortisone, ascorbic acid (vitamin C), and thiamine (vitamin B1); referred to as HAT

Control Arm

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

normal saline solution

Interventions

HAT

hydrocortisone, ascorbic acid (vitamin C), and thiamine (vitamin B1); referred to as HAT

Intervention Type: DRUG

Placebo

normal saline solution

Intervention Type: DRUG

Other Intervention Names

hydrocortisone, vitamin C, vitamin B1; NaCl 0.9%

Eligibility 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

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

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Kansas

OTHER

Sponsor Role: collaborator

Ascension Via Christi Hospitals Wichita, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Resch, M.D.

Role: PRINCIPAL_INVESTIGATOR

Surgeon

Locations

Ascension Via Christi Hospital - St. Francis Campus

Wichita, Kansas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

KUVC1814

Identifier Type: -

Identifier Source: org_study_id