Back to resultsHAT for the Treatment of Sepsis Associated With NASTI
Primary Purpose
Necrotizing Soft Tissue Infection, Sepsis
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
HAT
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Necrotizing Soft Tissue Infection
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria: (Adapted from Sevransky et. al's VICTAS protocol)
- 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
- 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]
- 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
Sites / Locations
- Ascension Via Christi Hospital - St. Francis CampusRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Treatment Arm
Control Arm
Arm 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: 1.5 g vitamin C every 6 hours for 4 days or until ICU discharge 50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days) 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.
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).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Duration of vasopressor therapy
The duration of vasopressor therapy is measured after date of randomization in hours and minutes from the initiation of vasopressor therapy until the termination of vasopressor therapy.
Requirement for renal replacement therapy in patients with Acute Kidney Injury (AKI)
This is a binary variable the will record whether the patient did or did not have a requirement for renal replacement therapy in patients with Acute Kidney Injury (AKI).
ICU length of stay (LOS)
ICU LOS will be measured by the date and time the patient was admitted to the ICU and by the date and time the patient was discharged from the ICU.
Change in serum procalcitonin (PCT) over first 72 hours
This is a binary variable that will show whether there was a change in serum procalcitonin (PCT) over first 72 hours.
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)
This is a group of variables that will show whether there was a change in SOFA score over the 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).
Procalcitonin Clearance
Procalcitonin clearance (formula = initial PCT - 72 hour PCT divided by initial PCT x 100)
Number of wound related surgeries
This is a variable that will show the count of wound related surgeries during the time the patient is admitted to the hospital.
Wound status at time of hospital discharge: Open or Closed
This is a binary variable that shows whether the wound status at time of hospital discharge is open or closed.
Full Information
NCT ID
NCT05157360
First Posted
October 28, 2021
Last Updated
January 31, 2023
Sponsor
Ascension Via Christi Hospitals Wichita, Inc.
Collaborators
The University of Kansas School of Medicine - Wichita
1. Study Identification
Unique Protocol Identification Number
NCT05157360
Brief Title
HAT for the Treatment of Sepsis Associated With NASTI
Official Title
Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Sepsis Associated With Acute Necrotizing Soft Tissue Infections, The NASTI HAT Trial
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 10, 2021 (Actual)
Primary Completion Date
September 10, 2024 (Anticipated)
Study Completion Date
October 10, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ascension Via Christi Hospitals Wichita, Inc.
Collaborators
The University of Kansas School of Medicine - Wichita
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
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:
Duration of vasopressor therapy
Requirement for renal replacement therapy in patients with Acute Kidney Injury (AKI)
ICU length of stay (LOS)
Change in serum procalcitonin (PCT) over first 72 hours
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)
Procalcitonin clearance (formula = initial PCT - 72 hour PCT divided by initial PCT x 100)
Number of wound related surgeries
Wound status at time of hospital discharge:
Open
Closed
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Necrotizing Soft Tissue Infection, Sepsis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
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.
Allocation
Randomized
Enrollment
132 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment Arm
Arm Type
Experimental
Arm 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:
1.5 g vitamin C every 6 hours for 4 days or until ICU discharge
50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days)
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.
Arm Title
Control Arm
Arm Type
Placebo Comparator
Arm 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).
Intervention Type
Drug
Intervention Name(s)
HAT
Other Intervention Name(s)
hydrocortisone, vitamin C, vitamin B1
Intervention Description
hydrocortisone, ascorbic acid (vitamin C), and thiamine (vitamin B1); referred to as HAT
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
NaCl 0.9%
Intervention Description
normal saline solution
Primary Outcome Measure Information:
Title
Hospital Survival
Description
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.
Time Frame
Outcome is measured from date of randomization to date of discharge or date of death, whichever comes first, assessed up to 24 months.
Secondary Outcome Measure Information:
Title
Duration of vasopressor therapy
Description
The duration of vasopressor therapy is measured after date of randomization in hours and minutes from the initiation of vasopressor therapy until the termination of vasopressor therapy.
Time Frame
Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, assessed up to 24 months.
Title
Requirement for renal replacement therapy in patients with Acute Kidney Injury (AKI)
Description
This is a binary variable the will record whether the patient did or did not have a requirement for renal replacement therapy in patients with Acute Kidney Injury (AKI).
Time Frame
Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, assessed up to 24 months.
Title
ICU length of stay (LOS)
Description
ICU LOS will be measured by the date and time the patient was admitted to the ICU and by the date and time the patient was discharged from the ICU.
Time Frame
Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, assessed up to 24 months.
Title
Change in serum procalcitonin (PCT) over first 72 hours
Description
This is a binary variable that will show whether there was a change in serum procalcitonin (PCT) over first 72 hours.
Time Frame
Over the first 72 hours from admission.
Title
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)
Description
This is a group of variables that will show whether there was a change in SOFA score over the 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).
Time Frame
Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, assessed up to 24 months.
Title
Procalcitonin Clearance
Description
Procalcitonin clearance (formula = initial PCT - 72 hour PCT divided by initial PCT x 100)
Time Frame
Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, assessed up to 24 months.
Title
Number of wound related surgeries
Description
This is a variable that will show the count of wound related surgeries during the time the patient is admitted to the hospital.
Time Frame
Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, assessed up to 24 months.
Title
Wound status at time of hospital discharge: Open or Closed
Description
This is a binary variable that shows whether the wound status at time of hospital discharge is open or closed.
Time Frame
Assessed at the time of discharge for each individual patient. Patients will be discharged throughout the study so this measure will be assessed up to 24 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria: (Adapted from Sevransky et. al's VICTAS protocol)
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
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]
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Thomas Resch, M.D.
Phone
316-263-0296
Email
TResch@wsspa.com
First Name & Middle Initial & Last Name or Official Title & Degree
Stephen D. Helmer, Ph.D.
Phone
316-268-5457
Email
Stephen.Helmer@Ascension.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Resch, M.D.
Organizational Affiliation
Surgeon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ascension Via Christi Hospital - St. Francis Campus
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
HAT for the Treatment of Sepsis Associated With NASTI
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