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.

← Back to Search

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

Must not have

Therapy with an immunosuppressive agent, including chemotherapy, biological therapies or an experimental drug or device within the past 6 weeks

Diagnosis of acute drug or toxin-induced liver injury

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 180 days

Awards & highlights

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.

Eligibility Criteria

Inclusion Criteria

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

Select...

I am between 1 and 17 years old.

Select...

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

Exclusion Criteria

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

Select...

I haven't taken any immunosuppressive drugs, including chemotherapy, in the last 6 weeks.

Select...

I have liver damage caused by a drug or toxin.

Select...

I have been diagnosed with acute Wilson disease.

Select...

I have received a solid organ or stem cell transplant.

Select...

I have been diagnosed with aplastic anemia before joining this study.

Select...

I have liver damage caused by reduced blood flow.

Select...

I am HIV positive or have been diagnosed with AIDS.

Select...

I currently have sepsis.

Select...

I have been diagnosed with autoimmune hepatitis.

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)

Side effects data

From 2023 Phase 1 & 2 trial • 307 Patients • NCT02348216

88%

Pyrexia

58%

Hypotension

54%

Anaemia

50%

Headache

50%

Fatigue

50%

Neutropenia

50%

Nausea

50%

Decreased appetite

46%

Vomiting

46%

Hypocalcaemia

42%

Hyponatraemia

38%

Hypoalbuminaemia

38%

Dizziness

33%

Confusional state

33%

Diarrhoea

33%

White blood cell count decreased

33%

Hypokalaemia

33%

Febrile neutropenia

33%

Tachycardia

29%

Chills

29%

Neutrophil count decreased

25%

Cough

25%

Tremor

25%

Hyperglycaemia

25%

Thrombocytopenia

25%

Hypophosphataemia

25%

Encephalopathy

25%

Lymphocyte count decreased

21%

Platelet count decreased

21%

Alanine aminotransferase increased

21%

Constipation

21%

Aspartate aminotransferase increased

21%

Hypoxia

17%

Dyspnoea

17%

Hypertension

17%

Upper respiratory tract infection

17%

Weight decreased

17%

Somnolence

17%

Hypomagnesaemia

17%

Dehydration

17%

Aphasia

17%

Pain in extremity

13%

Pneumonia

13%

Leukopenia

13%

Dry mouth

13%

Agitation

13%

Hypogammaglobulinaemia

13%

Herpes zoster

13%

Myalgia

13%

Anxiety

13%

Abdominal pain

Blood creatinine increased

Pruritus

Oropharyngeal pain

Muscular weakness

Myelodysplastic syndrome

Fall

Non-cardiac chest pain

Oedema peripheral

Insomnia

Dysuria

Back pain

Hypermagnesaemia

Dysgeusia

Conjunctivitis

Cardiac arrest

Photophobia

Electrocardiogram QT prolonged

Disturbance in attention

Abdominal distension

Asthenia

Memory impairment

Vision blurred

Sinus tachycardia

Ventricular arrhythmia

Sinus bradycardia

Arthralgia

Sinusitis

Clostridium difficile colitis

Mood altered

Nasopharyngitis

Depression

Brain injury

Abdominal pain upper

Pain

Urinary tract infection

Catheter site pain

Swelling

Blood alkaline phosphatase increased

Hyperkalaemia

Hypernatraemia

Disorientation

Restlessness

Upper-airway cough syndrome

Night sweats

Rectal haemorrhage

Peripheral sensory neuropathy

Pleural effusion

Rash

Serum ferritin increased

Respiratory distress

Pancytopenia

Atrial fibrillation

Dyspepsia

Flatulence

Hyperhidrosis

Hemiparesis

Pulmonary embolism

Neck pain

Hiccups

Rhinitis allergic

Lung infection

Local swelling

Candida infection

Blood bilirubin increased

Dysarthria

Mental status changes

Urinary incontinence

Tachypnoea

Acidosis

Nasal congestion

Presyncope

Device related sepsis

Delirium

Anal incontinence

Sepsis

Infusion related reaction

Urine output decreased

100%

80%

60%

40%

20%

Study treatment Arm

Phase 2 (Pivotal Study): Cohort 2

Phase 2 (Safety Management Study): Cohort 3

Phase 2 (Safety Management Study): Cohort 4

Phase 2 (Safety Management Study): Cohort 5

Phase 2 (Safety Management Study): Cohort 6

Retreatment Axicabtagene Ciloleucel: Phase 1

Phase 2 (Pivotal Study): Cohort 1

Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 2

Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 1

Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy

Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 4

Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 5

Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 3

Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 6

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

High-dose methylprednisolone

2015

Completed Phase 2

~310

Prednisolone

2005

Completed Phase 4

~2720

Methylprednisolone

2015

Completed Phase 4

~2280

Diphenhydramine

2002

Completed Phase 4

~1140

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

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.