HAT for the Treatment of Sepsis Associated With NASTI

NCT05157360 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: KUVC1814
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Necrotizing Soft Tissue Infection; Sepsis

Outcome Measures

Primary Outcomes (1)

• Hospital Survival

  Hospital survival is a binary variable showing whether the patient survived their time in the hospital. Hospital survival will be assessed from date of randomization until the date of discharge or date of death from any cause, whichever comes first, assessed up to 24 months.

  Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.

Secondary Outcomes (8)

• Duration of Vasopressor Therapy

  Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.

• Requirement for Renal Replacement Therapy in Patients With Acute Kidney Injury (AKI)

  Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.

• ICU Length of Stay (LOS)

  Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.

• Change in Serum Procalcitonin (PCT) Over First 72 Hours

  Over the first 72 hours from admission.

• Change in Sequential Organ Failure Assessment (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)

  Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.

Study Arms (2)

Treatment Arm

EXPERIMENTAL

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.

Drug: HAT

Control Arm

PLACEBO COMPARATOR

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).

Drug: Placebo

Interventions

HAT DRUG

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

Also known as: hydrocortisone, vitamin C, vitamin B1

Treatment Arm

Placebo DRUG

normal saline solution

Also known as: NaCl 0.9%

Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Age \< 18 years of age
• Weight \< 40 kg
• Prior enrollment in this study or current enrollment in another study of any kind
• 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
• Sepsis deemed unlikely
• Known allergy or known contraindication to vitamin C, thiamine, or corticosteroids \[including previous history or active diagnosis of primary hyperoxaluria and/or oxalate nephropathy, or known/suspected ethylene glycol ingestion, or known glucose-6-phosphate dehydrogenase (G6PD) deficiency\]
• 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
• 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.)
• Kidney Stone(s) of any kind
• History of Oxalate Kidney Stone(s)
• Pregnancy or known active breastfeeding
• Prisoner or Incarceration
• Inability or unwillingness of subject or legal surrogate/representative to give written informed consent

Sponsors & Collaborators

• Ascension Via Christi Hospitals Wichita, Inc.: lead
• University of Kansas: collaborator

Study Sites (1)

Ascension Via Christi Hospital - St. Francis Campus

Wichita, Kansas, 67214, United States

Location

MeSH Terms

Conditions

Sepsis

Interventions

Hydrocortisone; Ascorbic Acid; Thiamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Due to the small number of participants enrolled, the findings are observational only.

Results Point of Contact

• Title: Dr. Thomas Resch
• Organization: Department of Surgery, University of Kansas School of Medicine-Wichita

tresch@wsspa.com

316-268-5990

Study Officials

• Thomas Resch, M.D.

  Surgeon

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: A randomization list will be used to show whether patients will be in group A or B. Only the Research Scientist who made the randomization list and the Pharmacy will know what group patients are in. The Burn Program Coordinator will get consent and enroll patients to the study. After that, the Burn Program Coordinator will call the pharmacy and report what group the patient is enrolled in, A or B. Then, the pharmacy will order the respective medications. The doctors and nurses providing care for the patients will not know who is in what treatment group, and neither will the patients.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2021
• First Posted: December 15, 2021
• Study Start: September 10, 2021
• Primary Completion: May 16, 2023
• Study Completion: May 16, 2023
• Last Updated: July 24, 2024
• Results First Posted: July 24, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)