TReatment for ImmUne Mediated PathopHysiology

Conditions

• Acute Liver Failure
• Acute Liver Injury
• Fulminant Hepatic Failure
• Hepatic Encephalopathy
• Immune Dysregulation

Eligibility Criteria

Sex

ALL

Age

1 Year - 18 Years

Healthy Volunteers

Not accepted

Interventions

• High-dose methylprednisolone — DRUG
  Subjects in the high-dose methylprednisolone arm will receive an initial dose of methylprednisolone IV 10 mg/kg/day for 3 days and 5 mg/kg/day on Day 4. Normal saline will be used as placebo pre-medications and infusions given at the same volume and duration as the eATG infusions.
• Equine anti-thymocyte globulin — DRUG
  Subjects will receive eATG IV 40 mg/kg/day on Days 1- 4. Day 1 eATG infusion is run over 8 hours and Day 2-4 infusions are run over 4 hours.
• Prednisolone — DRUG
  Subjects will receive prednisolone 1 mg/kg on Days 5-13 followed by a gradual taper with discontinuation at 42 Days as indicated below. Days 5 - 13 Prednisolone PO 1 mg/kg/day (max 50 mg/day) Days 14- 20 Prednisolone PO 0.5 mg/kg/day (max 25 mg/day) Days 21 - 27 Prednisolone PO 0.3 mg/kg/day (max 15 mg/day) Days 28 - 34 Prednisolone PO 0.1 mg/kg/day (max 5 mg/day) Days 35 - 41 Prednisolone PO 0.1 mg/kg every OTHER day (max 5 mg every other day) Day 42 Discontinue
• Placebo for prednisolone — DRUG
  Subjects will receive 1 mg/kg/day of oral placebo for prednisolone on days 5-13 followed by a gradual taper to discontinuation at 42 days as indicated below. Subjects receiving oral placebo will be given a solution that closely resembles the treatment drug. Days 5 - 13 Placebo for Prednisolone PO 1 mg/kg/day (max 50 mg/day) Days 14- 20 Placebo for Prednisolone PO 0.5 mg/kg/day (max 25 mg/day) Days 21 - 27 Placebo for Prednisolone PO 0.3 mg/kg/day (max 15 mg/day) Days 28 - 34 Placebo for Prednisolone PO 0.1 mg/kg/day (max 5 mg/day) Days 35 - 41 Placebo for Prednisolone PO 0.1 mg/kg every OTHER day (max 5 mg every other day) Day 42 Discontinue
• Placebo for infusions — DRUG
  Subjects randomized to the supportive care alone arm will receive normal saline in place of all study treatments (skin test, premedication and IV infusions) on Days 1-4 given at the same volume and duration as the eATG infusions.
• Diphenhydramine — DRUG
  Subjects in the eATG arm will receive pre-treatment medication diphenhydramine IV 1 mg/kg prior to start of eATG infusion.
• Methylprednisolone — DRUG
  Subjects in the eATG arm will receive pre-treatment medication methylprednisolone IV 1 mg/kg prior to start of eATG infusion.

Study Details

TReatment for ImmUne Mediated PathopHysiology (TRIUMPH) is a multi-center, three arm, randomized, controlled trial of immunosuppressive therapy for children with acute liver failure. The study will determine if suppressing inflammatory responses with either corticosteroids or equine anti-thymocyte globulin therapy improves survival for children with this rare, life-threatening condition.

Key Dates

Start date

Feb 9, 2022

Status verified

May 2026

Primary completion

Aug 31, 2026

Completion

Feb 28, 2027

Study Design

Enrollment

163 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: High-dose methylprednisolone
  Intravenous methylprednisolone at an initial dose of 10 mg/kg/day for 3 days, 5 mg/kg/day on day 4.
• Experimental: Equine anti-thymocyte globulin
  Intravenous equine anti-thymocyte globulin at a dose of 40 mg/kg/day for 4 days.
• Placebo Comparator: Supportive care
  Supportive care will be administered as determined by the clinical team at participating clinical sites in accordance with their local practices and standards.
• No Intervention: Observational Cohort
  This study includes a prospective observational cohort study of patients with Pediatric Acute Liver Failure who meet the randomized controlled trial eligibility criteria and are willing to provide longitudinal observational data. Patients who provide consent will receive the enrolling institution's standard of care and will be followed for up to 90-days for clinical (observational) assessments and biospecimen collection for the biorepository.

Primary Outcome Measure

Survival with native liver (SNL) [ Time Frame: 21 days ]

Central Contacts

• Katie Neighbors, MPH
  312-227-4557
  [email protected]
• Caitlin Schaffner, MPH
  843-792-6588
  [email protected]

Locations (24)

Find similar trials in Los Angeles, CA

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