RecruitingPhase 2NCT04862221

TReatment for ImmUne Mediated PathopHysiology

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


Sponsor

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

Enrollment

163 participants

Start Date

Feb 9, 2022

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 1 YearMax Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study, called TRIUMPH, investigates treatments for acute liver failure in children — a rare but life-threatening emergency where the liver rapidly loses function. The study tests immune-modulating therapies (treatments that target the overactive immune response) in children aged 1–17 who have sudden severe liver injury without a clear cause, which may be immune-driven. Finding effective treatments for this condition is urgent, as liver transplant is often the only life-saving option without an alternative therapy. Children with acute liver failure who meet specific liver function criteria will be enrolled and randomized to receive either standard care or an investigational immune-modulating treatment. Patients are closely monitored for liver recovery, need for transplant, and survival. You may be eligible if: - You are between 1 and 18 years old - You have acute liver injury of 6 weeks or less duration with liver dysfunction criteria met (abnormal INR with or without brain symptoms) - You or your legal guardian consent to participate You may NOT be eligible if: - Your liver injury is due to hepatitis A, B, C, E, herpes, adenovirus, or known metabolic/autoimmune disease - You have aplastic anemia, active cancer, or have had organ/stem cell transplant - You are on immunosuppressive therapy or chemotherapy within the past 6 weeks - You are pregnant or breastfeeding - You have HIV or AIDS Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGHigh-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.

DRUGEquine 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.

DRUGPrednisolone

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

DRUGPlacebo 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

DRUGPlacebo 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.

DRUGDiphenhydramine

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

DRUGMethylprednisolone

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


Locations(24)

Children's Hospital Los Angeles

Los Angeles, California, United States

Lucile Packard Children's Hospital

Palo Alto, California, United States

Rady Children's Hospital

San Diego, California, United States

University of California San Francisco Benioff Children's Hospital

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Yale New Haven Children's Hospital

New Haven, Connecticut, United States

Children's Healthcare of Atlanta - Arthur M. Blank Hospital

Atlanta, Georgia, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Children's Hospital Boston

Boston, Massachusetts, United States

The Children's Mercy Hospital

Kansas City, Missouri, United States

St. Louis Children's Hospital

St Louis, Missouri, United States

The Mount Sinai Medical Center

New York, New York, United States

NYP Morgan Stanley Children's Hospital

New York, New York, United States

Duke University Medical Center - Duke Children's

Durham, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Cleveland Clinic Children's

Cleveland, Ohio, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Children's Hospital Vanderbilt

Nashville, Tennessee, United States

UT Southwestern Medical Center Children's Health

Dallas, Texas, United States

Texas Children's Hospital

Houston, Texas, United States

Primary Children's Medical Center

Salt Lake City, Utah, United States

Seattle Children's Hospital

Seattle, Washington, United States

View Full Details on ClinicalTrials.gov

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NCT04862221


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