TReatment for ImmUne Mediated PathopHysiology (TRIUMPH)

J
Jean Molleston, MD

Primary Investigator

Enrolling By Invitation
1-18 years
All
Phase 2
160 participants needed
2 Locations

Brief description of study

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

Detailed description of study

Pediatric Acute Liver Failure (PALF) is a rare, devastating condition that affects and 250 children per year in North America, causing death in approximately 15% and thed for liver transplantation in an additional 20-30%. In the majority of cases, a specificuse of the liver injury is never determined. Recent research supports the theory that manyhese patients have liver injury related to a hyperinflammatory immune response toveryday infections or environmental exposures. There is strong evidence to show that equinehymocyte globulin and methylprednisolone slow the body's response to inflammation andve the recovery of patients with other immune disorders and thus, may help patients withute liver failure.
This is a phase 2b, double-blind, three arm, randomized, placebo controlled trial withd response adaptive randomization. The primary objective is to determine they and safety of high-dose methylprednisolone or equine anti-thymocyte globulin (eATGATGAM®) as compared to supportive care alone (placebo) for the treatment of acute liverure in pediatric patients.
Approximately 160 patients who are equal to or greater than ≥ 1 and less than ≤ 18 years ofge with pediatric acute liver failure (PALF) of undetermined etiology will be randomized tove either high-dose methylprednisolone (Treatment 1) or eATG (ATGAM®) (Treatment 2) orupportive care alone (Treatment 3) on days 1 to 4 after study enrollment, followed by a gradual prednisolone taper (for the two active treatment arms 1 and 2) or a placebo taper (for treatment arm 3) on days 5 to 42.
The follow-up period includes visits at 1 week (Day 7), 2 weeks (Day 14), and 3 weeks (Day 21) after the day the participant started in the study. Early follow-up assessments will bed either in the inpatient or ambulatory setting since some participants may be discharged before Day 7. In addition, families will be contacted by phone or email tohedule each follow-up at the study site for the 6 week, 3 month, 6 month and 12 month study visits.
The findings of this trial have the potential to shift the treatment paradigm in PALF anddvance the basic understanding of immune dysregulation disorders in childhood. The networkudes 20 of the largest and most active pediatric liver centers in the US who haveganized to support rigorous testing of the efficacy and safety of immunosuppressive therapyhese patients.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Riley, Acute Liver Failure, Fulminant Hepatic Failure, Hepatic Encephalopathy, Acute Liver Injury, Immune Dysregulation
  • Age: Between 1 Year - 18 Years
  • Gender: All

Inclusion Criteria:
  1. Patient with liver injury of ≤ 6 weeks duration resulting in an internationalzed ratio (INR) of ≥ 1.5 and < 2.0 (not corrected by vitamin K) with evidencehepatic encephalopathy (HE) or INR ≥ 2.0 without evidence of HE.
  2. Age is greater than or equal to 1 year and less than 18 years of age.
  3. Patient or their legally authorized representative(s) (LAR) must consent (and assent,ble) to be in the study and must have signed and dated an approved informedwhich conforms to federal and institutional guidelines.
  4. Females of reproductive potential should not plan on conceiving children during theudy and must agree to use a medically accepted form of contraception.
Exclusion Criteria:
  1. Evidence of active infection with Hepatitis A, B, C, E or evidence of acute herpesvirus (HSV) or adenovirus infection
  2. Travel within the past 3 months to an area highly endemic for Hepatitis E
  3. Diagnosis of hemophagocytic lymphohistiocytosis (HLH) Note: Patients with a history ofguinity and/or central nervous system (CNS) dysfunction that is exaggeratedd to the degree of liver dysfunction (as judged by the site investigator) willbe enrolled until results of rapid genetic testing are available. Turn-around timegenetic testing results is estimated to be 72-96 hours.
  4. Aplastic anemia as defined by standardized criteria [1] diagnosed prior to enrollment
  5. Diagnosis of autoimmune Hepatitis (AIH)
  6. Diagnosis of acute Wilson disease
  7. Diagnosis of inborn error of metabolism Note: Suspicion of metabolic disease is not anusion for entry into the Trial.
  8. Diagnosis of acute drug or toxin-induced liver injury
  9. History of recreational drug use within the past 4 weeks
  10. Therapy with an immunosuppressive agent, including chemotherapy, biological therapiesdrug or device within the past 6 weeks
  11. Liver injury due to ischemia
  12. Liver dysfunction diagnosed more than 6 weeks prior to screening
  13. History of allergy to horse dander
  14. Sepsis
  15. Imminent risk of death as judged by the clinical site investigator, including but notd to; signs of cerebral herniation at the time of enrollment and presence ofble arterial hypotension
  16. Solid organ or stem cell transplant recipient
  17. Pregnant or breast-feeding at the time of proposed study entry
  18. Clinical AIDS or HIV positive
  19. History of any form of malignant neoplasm and/or tumors treated within five yearsudy entry (other than non-melanoma skin cancer or in situ cervical cancer)where there is current evidence of recurrent or metastatic disease
  20. Received a live-virus vaccine within 4 weeks of study entry
  21. Positive test result for the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection
  22. Psychiatric or addictive disorders that would preclude obtaining informed/assent
  23. Patient is unwilling or unable to adhere with study requirements and procedures
  24. Currently receiving other experimental therapies

Updated on 13 Sep 2024. Study ID: PALF IRN/TRIUMPH, PGI-NIDDK-TRIUMPH, 12567
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