A Phase 2b, Double-Blind, Three Arm, Randomized, Placebo Controlled Trial With Restricted Response Adaptive Randomization Testing the Efficacy and Safety of High Dose Methylprednisolone or Equine Anti-Thymocyte Globulin as Treatment for Acute Liver Failure in Pediatric Patients

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Summary

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.

Description

Pediatric Acute Liver Failure (PALF) is a rare, devastating condition that affects an estimated 250 children per year in North America, causing death in approximately 15% and the need for liver transplantation in an additional 20-30%. In the majority of cases, a specific cause of the liver injury is never determined. Recent research supports the theory that many of these patients have liver injury related to a hyperinflammatory immune response to everyday infections or environmental exposures. There is strong evidence to show that equine anti-thymocyte globulin and methylprednisolone slow the…

Interventions

Drug

High-dose methylprednisolone

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.

Drug

Equine anti-thymocyte globulin

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.

Drug

Prednisolone

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

Drug

Placebo for prednisolone

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

Drug

Placebo for infusions

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.

Drug

Diphenhydramine

Subjects in the eATG arm will receive pre-treatment medication diphenhydramine IV 1 mg/kg prior to start of eATG infusion.

Drug

Methylprednisolone

Subjects in the eATG arm will receive pre-treatment medication methylprednisolone IV 1 mg/kg prior to start of eATG infusion.

A Phase 2b, Double-Blind, Three Arm, Randomized, Placebo Controlled Trial With Restricted Response Adaptive Randomization Testing the Efficacy and Safety of High Dose Methylprednisolone or Equine Anti-Thymocyte Globulin as Treatment for Acute Liver Failure in Pediatric Patients

Summary

Description

Eligibility

Interventions

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