TReatment for ImmUne Mediated PathopHysiology
TRIUMPH
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
2 other identifiers
interventional
163
1 country
24
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2022
Longer than P75 for phase_2
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 23, 2021
CompletedFirst Posted
Study publicly available on registry
April 27, 2021
CompletedStudy Start
First participant enrolled
February 9, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 1, 2027
March 10, 2026
March 1, 2026
4.5 years
April 23, 2021
March 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Survival with native liver (SNL)
Alive and without a liver transplant 21 days following randomization
21 days
Secondary Outcomes (1)
Survival with native liver (SNL)
180 days
Study Arms (4)
High-dose methylprednisolone
EXPERIMENTALIntravenous methylprednisolone at an initial dose of 10 mg/kg/day for 3 days, 5 mg/kg/day on day 4.
Equine anti-thymocyte globulin
EXPERIMENTALIntravenous equine anti-thymocyte globulin at a dose of 40 mg/kg/day for 4 days.
Supportive care
PLACEBO COMPARATORSupportive care will be administered as determined by the clinical team at participating clinical sites in accordance with their local practices and standards.
Observational Cohort
NO INTERVENTIONThis 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.
Interventions
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.
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.
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
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
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.
Subjects in the eATG arm will receive pre-treatment medication diphenhydramine IV 1 mg/kg prior to start of eATG infusion.
Subjects in the eATG arm will receive pre-treatment medication methylprednisolone IV 1 mg/kg prior to start of eATG infusion.
Eligibility Criteria
You may qualify if:
- Patient with liver injury of ≤ 6 weeks duration resulting in an international normalization ratio (INR) of ≥ 1.5 or \< 2.0 (not corrected by vitamin K) with evidence of hepatic encephalopathy (HE), INR of ≥ 1.5 or \< 2.0 for at least 7 days duration without evidence of HE or INR ≥ 2.0 without evidence of HE.
- Age is greater than or equal to 1 year and less than 18 years of age.
- Patient or their legally authorized representative(s) (LAR) must consent (and assent, if applicable) to be in the study and must have signed and dated an approved informed consent form which conforms to federal and institutional guidelines.
- Females of reproductive potential should not plan on conceiving children during the study and must agree to use a medically accepted form of contraception.
You may not qualify if:
- Evidence of active infection with Hepatitis A, B, C, E or evidence of acute herpes simplex virus (HSV) or adenovirus infection
- Travel within the past 3 months to an area highly endemic for Hepatitis E
- Diagnosis of hemophagocytic lymphohistiocytosis (HLH) Note: Patients with a history of consanguinity and/or central nervous system (CNS) dysfunction that is exaggerated compared to the degree of liver dysfunction (as judged by the site investigator) will not be enrolled until results of rapid genetic testing are available. Turn-around time for genetic testing results is estimated to be 72-96 hours.
- Aplastic anemia as defined by standardized criteria \[1\] diagnosed prior to enrollment
- Diagnosis of autoimmune Hepatitis (AIH)
- Diagnosis of acute Wilson disease
- Diagnosis of acute drug or toxin-induced liver injury
- History of recreational drug use within the past 4 weeks
- Therapy with an immunosuppressive agent, including chemotherapy, biological therapies or an experimental drug or device within the past 6 weeks
- Liver injury due to ischemia
- Liver dysfunction diagnosed more than 6 weeks prior to screening
- History of allergy to horse dander
- Sepsis
- Imminent risk of death as judged by the clinical site investigator, including but not limited to; signs of cerebral herniation at the time of enrollment and presence of intractable arterial hypotension
- Solid organ or stem cell transplant recipient
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (24)
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Lucile Packard Children's Hospital
Palo Alto, California, 94304, United States
Rady Children's Hospital
San Diego, California, 92123, United States
University of California San Francisco Benioff Children's Hospital
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Yale New Haven Children's Hospital
New Haven, Connecticut, 06510, United States
Children's Healthcare of Atlanta - Arthur M. Blank Hospital
Atlanta, Georgia, 30322, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Children's Hospital Boston
Boston, Massachusetts, 02115, United States
The Children's Mercy Hospital
Kansas City, Missouri, 64108, United States
St. Louis Children's Hospital
St Louis, Missouri, 63110, United States
The Mount Sinai Medical Center
New York, New York, 10029, United States
NYP Morgan Stanley Children's Hospital
New York, New York, 10032, United States
Duke University Medical Center - Duke Children's
Durham, North Carolina, 27710, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Cleveland Clinic Children's
Cleveland, Ohio, 44195, United States
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224, United States
Children's Hospital Vanderbilt
Nashville, Tennessee, 37232, United States
UT Southwestern Medical Center Children's Health
Dallas, Texas, 75235, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Primary Children's Medical Center
Salt Lake City, Utah, 84112, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Estella M Alonso, MD
Ann & Robert H Lurie Children's Hospital of Chicago
- PRINCIPAL INVESTIGATOR
Valerie L Durkalski-Mauldin, PhD
Medical University of South Carolina
- STUDY DIRECTOR
Ed Doo, MD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- STUDY DIRECTOR
Averell Sherker, MD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 23, 2021
First Posted
April 27, 2021
Study Start
February 9, 2022
Primary Completion (Estimated)
August 1, 2026
Study Completion (Estimated)
February 1, 2027
Last Updated
March 10, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- Release of the public use dataset will follow the NIDDK guidelines that study data analyzed for publications must be shared with the broader scientific community at the time of publication. Also, the study data analyzed for publications will be submitted to the NIDDK-CR when the manuscript is accepted for publication or at the time of publication.
Data will be available at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repository. The public use dataset, along with the study protocol, the data dictionary, annotated case report forms and a brief set of instructions ("Readme" file) will be provided.