What is the mechanism of action of this treatment?

Corticosteroids and equine anti-thymocyte globulin (ATG) are common treatments for liver injury due to their immunosuppressive properties. Corticosteroids provide broad immunosuppression and anti-inflammatory effects, which help reduce overall immune-mediated damage to liver cells, crucial for preventing further liver injury and promoting healing. Equine ATG specifically targets T-cells, reducing their activity and proliferation. This targeted approach is important because T-cells are key players in the immune response that can exacerbate liver injury. By diminishing T-cell activity, ATG helps decrease the immune-mediated attack on the liver, potentially improving patient outcomes.

What side effects are associated with this type of intervention?

Corticosteroids, used for their broad immunosuppressive and anti-inflammatory effects, can cause side effects such as hyperglycemia, increased susceptibility to infections, bone loss, fractures, and neuropsychiatric issues. Equine anti-thymocyte globulin (ATG), which provides T-cell specific immunosuppression, can lead to side effects including serum sickness, anaphylaxis, fever, chills, leukopenia, and increased risk of infections. Both treatments aim to modulate the immune response but come with significant potential adverse effects that need to be managed carefully.

What prior FDA approvals exist?

Corticosteroids like prednisone have been approved for their broad immunosuppressive and anti-inflammatory effects in treating liver conditions such as autoimmune hepatitis. Equine anti-thymocyte globulin, which provides T-cell specific immunosuppression, is used in severe cases like acute liver failure and organ transplant rejection. These treatments help manage inflammation and immune-mediated liver damage.

What other types of research exist?

Promising novel alternatives to corticosteroids and equine anti-thymocyte globulin for liver injury patients in 2024 may include IL-1 receptor antagonists like anakinra and monoclonal antibodies targeting specific immune pathways, such as TNF inhibitors or IL-6 inhibitors. These therapies provide targeted immunosuppression and anti-inflammatory effects.

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Immunosuppressant

Immune Suppression Therapy for Acute Liver Failure (TRIUMPH Trial)

Phase 2

Recruiting

Led By Valerie L Durkalski-Mauldin, PhD

Research Sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Eligibility Criteria Checklist

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

Must have

Age is greater than or equal to 1 year and less than 18 years of age

Patient with liver injury of ≤ 6 weeks duration resulting in an international normalized ratio (INR) of ≥ 1.5 and < 2.0 (not corrected by vitamin K) with evidence of hepatic encephalopathy (HE) or INR ≥ 2.0 without evidence of HE

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 180 days

Awards & highlights

TRIUMPH Trial Summary

This trial will help determine if suppressing the immune response with either corticosteroids or equine anti-thymocyte globulin therapy helps improve survival rates for children with acute liver failure.

Who is the study for?

The TRIUMPH study is for children aged 1-17 with acute liver failure, who agree to use contraception if applicable. They must consent to participate and have a specific level of liver injury. Excluded are those with psychiatric disorders, imminent death risk, recent drug use or immunosuppressive therapy, organ transplants, COVID-19 infection, certain infections or vaccinations, allergies to horse dander, pregnancy/breastfeeding women, HIV/AIDS patients, travelers to Hepatitis E regions recently.Check my eligibility

What is being tested?

TRIUMPH evaluates the effectiveness of immunosuppressants (high-dose methylprednisolone or equine anti-thymocyte globulin) versus placebo in improving survival rates among children with life-threatening acute liver failure. This randomized trial will compare three groups: one receiving corticosteroids; another getting equine anti-thymocyte globulin; and a third given placebos.See study design

What are the potential side effects?

Possible side effects include immune system suppression leading to increased infection risk; allergic reactions especially related to horse-derived products; hormonal imbalances due to steroids like weight gain and mood changes; high blood sugar levels; increased appetite; trouble sleeping.

TRIUMPH Trial Eligibility Criteria

Inclusion Criteria

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

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I am between 1 and 17 years old.

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I have liver injury with specific blood clotting test results and may or may not have brain function changes due to liver failure.

TRIUMPH Trial Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 180 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~180 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 180 days for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Secondary outcome measures

Survival with native liver (SNL)

TRIUMPH Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: High-dose methylprednisoloneExperimental Treatment2 Interventions

Intravenous methylprednisolone at an initial dose of 10 mg/kg/day for 3 days, 5 mg/kg/day on day 4.

Group II: Equine anti-thymocyte globulinExperimental Treatment4 Interventions

Intravenous equine anti-thymocyte globulin at a dose of 40 mg/kg/day for 4 days.

Group III: Supportive carePlacebo Group2 Interventions

Supportive care will be administered as determined by the clinical team at participating clinical sites in accordance with their local practices and standards.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Prednisolone

2005

Completed Phase 4

~2720

Methylprednisolone

2015

Completed Phase 4

~2280

Diphenhydramine

2002

Completed Phase 4

~1170

0 / 2Eligibility 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

Corticosteroids and equine anti-thymocyte globulin (ATG) are common treatments for liver injury due to their immunosuppressive properties. Corticosteroids provide broad immunosuppression and anti-inflammatory effects, which help reduce overall immune-mediated damage to liver cells, crucial for preventing further liver injury and promoting healing. Equine ATG specifically targets T-cells, reducing their activity and proliferation. This targeted approach is important because T-cells are key players in the immune response that can exacerbate liver injury. By diminishing T-cell activity, ATG helps decrease the immune-mediated attack on the liver, potentially improving patient outcomes.

Chemical induction of hepatic apoptosis in rodents.Thymoquinone, an Active Constituent of Black Seed Attenuates CCl4 Induced Liver Injury in Mice via Modulation of Antioxidant Enzymes, PTEN, P53 and VEGF Protein.Herbal Compound "Jiedu Huayu" Reduces Liver Injury in Rats via Regulation of IL-2, TLR4, and PCNA Expression Levels.