What side effects are associated with this type of intervention?

Hydrocortisone can cause side effects such as hyperglycemia, increased risk of infection, gastrointestinal bleeding, and adrenal suppression. Ascorbic acid (vitamin C) is generally well-tolerated but can cause gastrointestinal disturbances like diarrhea and abdominal cramps at high doses. Thiamine is also well-tolerated, with rare side effects including allergic reactions and gastrointestinal upset. Combining these treatments aims to reduce inflammation, oxidative stress, and support cellular metabolism, but the overall efficacy and safety profile require further study.

What prior FDA approvals exist?

The FDA has approved several treatments for sepsis, but there are no specific approvals for the combination of hydrocortisone, ascorbic acid, and thiamine (HAT therapy). Hydrocortisone, a corticosteroid, is used to reduce inflammation in septic shock, and its use is supported by guidelines for critical illness-related corticosteroid insufficiency. Ascorbic acid (vitamin C) and thiamine (vitamin B1) have been studied for their potential benefits in reducing oxidative stress and supporting cellular metabolism, respectively, but they are not specifically approved by the FDA for sepsis treatment. Current research, including trials like HAT therapy, is investigating the efficacy of these combined treatments in sepsis management.

What other types of research exist?

Promising novel alternatives to HAT therapy for sepsis patients include: <ol> <li>Vasopressin: Used in combination with corticosteroids, vasopressin has shown potential in improving outcomes in septic shock.</li> <li></li> </ol> Norepinephrine: Preferred over dopamine for its efficacy and safety in managing septic shock. 3. Antifungal agents: For patients with suspected fungal infections, empirical antifungal therapy like micafungin may be considered. 4. Vitamin D3: Supplementation has shown potential in improving immune response and reducing inflammation. 5. Carbocysteine: May help reduce exacerbations in patients with concurrent COPD and sepsis. 6. Glucocorticoid therapy: Continued research into optimal dosing and patient selection is ongoing.

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HAT for Sepsis

Q: What is the mechanism of action of this treatment?

HAT therapy for sepsis includes hydrocortisone, ascorbic acid (vitamin C), and thiamine, each targeting different aspects of the disease. Hydrocortisone reduces inflammation by suppressing the immune response, which is crucial to prevent tissue damage. Ascorbic acid acts as an antioxidant, reducing oxidative stress and protecting cells from free radical damage. Thiamine supports cellular metabolism and energy production, which can be impaired in sepsis. These treatments are important as they address key pathological processes in sepsis, potentially improving patient outcomes by stabilizing cellular function, reducing inflammation, and mitigating oxidative damage.

Phase 1 & 2

Waitlist Available

Led By Thomas Resch, M.D.

Research Sponsored by Ascension Via Christi Hospitals Wichita, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Necrotizing soft tissue infection by clinical diagnosis and requiring surgical treatment

Sepsis by clinical diagnosis and/or by Sepsis-3 criteria, with source attributed to the wound

Must not have

Weight < 40 kg

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]

Timeline

Screening 3 weeks

Treatment Varies

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

Awards & highlights

Approved for 60 Other Conditions

All Individual Drugs Already Approved

Summary

This trial evaluates HAT therapy, which combines Hydrocortisone, Vitamin C, and Vitamin B1, in patients with severe infections like NSTI and sepsis. The treatment aims to reduce inflammation, support the immune system, and improve cell function. Hydrocortisone has been used in various treatments due to its anti-inflammatory properties, but its effectiveness can vary depending on the condition being treated.

Who is the study for?

This trial is for adults with sepsis and necrotizing soft tissue infections needing ICU care and surgery. It's not for those under 18, pregnant or breastfeeding women, prisoners, people with severe chronic diseases expected to live less than 30 days unrelated to sepsis, or anyone allergic to the study drugs. Participants must weigh over 40 kg and cannot be using high-dose vitamin C.

What is being tested?

The trial tests HAT therapy (a combination of vitamin C, thiamine, and corticosteroids) against a placebo in patients with acute necrotizing soft tissue infections (NSTI) complicated by sepsis. The goal is to see if HAT improves patient outcomes compared to a non-active treatment.

What are the potential side effects?

Possible side effects include reactions related to high doses of vitamins such as stomach upset or kidney stones in susceptible individuals. Corticosteroids can cause increased blood sugar levels, mood changes, insomnia, and higher infection risk.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a severe infection in my soft tissues that needs surgery.

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I have been diagnosed with sepsis originating from a wound.

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I am expected to be or am currently in intensive care.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I weigh less than 40 kg.

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I am willing to accept all forms of cardiovascular and respiratory support except intubation.

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My condition is not due to an infectious flesh-eating disease as confirmed by surgery or lab tests.

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I am not allergic to vitamin C, thiamine, or corticosteroids and do not have conditions that make these unsafe for me.

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I have had kidney stones made of oxalate.

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I am unable or unwilling to give my consent for participation.

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I have kidney stones.

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I am under 18 years old.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.

This trial's timeline: 3 weeks for screening, Varies for treatment, and outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Hospital Survival

Secondary study objectives

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)

Change in Serum Procalcitonin (PCT) Over First 72 Hours

Duration of Vasopressor Therapy

+5 more

Awards & Highlights

Approved for 60 Other Conditions

This treatment demonstrated efficacy for 60 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Treatment ArmExperimental Treatment1 Intervention

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 II: Control ArmPlacebo Group1 Intervention

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).

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

HAT therapy for sepsis includes hydrocortisone, ascorbic acid (vitamin C), and thiamine, each targeting different aspects of the disease. Hydrocortisone reduces inflammation by suppressing the immune response, which is crucial to prevent tissue damage. Ascorbic acid acts as an antioxidant, reducing oxidative stress and protecting cells from free radical damage. Thiamine supports cellular metabolism and energy production, which can be impaired in sepsis. These treatments are important as they address key pathological processes in sepsis, potentially improving patient outcomes by stabilizing cellular function, reducing inflammation, and mitigating oxidative damage.

Early administration of hydrocortisone, vitamin C, and thiamine in adult patients with septic shock: a randomized controlled clinical trial.Vitamin C, Hydrocortisone and Thiamine in Patients with Septic Shock (VITAMINS) trial: study protocol and statistical analysis plan.