Summary

Eligibility
for people ages 1-18 (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion
Principal Investigator
by Philip Rosenthal

Description

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.

Official Title

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

Details

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 body's response to inflammation and improve the recovery of patients with other immune disorders and thus, may help patients with acute liver failure. This is a phase 2b, double-blind, three arm, randomized, placebo controlled trial with restricted response adaptive randomization. The primary objective is to determine the efficacy and safety of high-dose methylprednisolone or equine anti-thymocyte globulin (eATG or ATGAM®) as compared to supportive care alone (placebo) for the treatment of acute liver failure in pediatric patients. Approximately 160 patients who are equal to or greater than ≥ 1 and less than ≤ 18 years of age with pediatric acute liver failure (PALF) of undetermined etiology will be randomized to receive either high-dose methylprednisolone (Treatment 1) or eATG (ATGAM®) (Treatment 2) or supportive 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 be performed 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 to schedule 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 and advance the basic understanding of immune dysregulation disorders in childhood. The network includes 20 of the largest and most active pediatric liver centers in the US who have organized to support rigorous testing of the efficacy and safety of immunosuppressive therapy for these patients.

Keywords

Acute Liver Failure Fulminant Hepatic Failure Hepatic Encephalopathy Acute Liver Injury Immune Dysregulation hepatic insufficiency liver diseases liver failure anti-thymocyte agents Liver Failure, Acute Brain Diseases Diphenhydramine Promethazine Methylprednisolone Methylprednisolone Acetate Methylprednisolone Hemisuccinate Prednisolone Prednisolone acetate Prednisolone hemisuccinate Prednisolone phosphate Antilymphocyte Serum High-dose methylprednisolone Equine anti-thymocyte globulin

Eligibility

You can join if…

Open to people ages 1-18

  1. Patient with liver injury of ≤ 6 weeks duration resulting in an international normalized ratio (INR) of ≥ 1.5 and < 2.0 (not corrected by vitamin K) with evidence of hepatic 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, 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.
  4. 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 CAN'T join if...

  1. Evidence of active infection with Hepatitis A, B, C, E or evidence of acute herpes simplex virus (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 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.
  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 an exclusion 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 therapies or an experimental drug 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 not limited to; signs of cerebral herniation at the time of enrollment and presence of intractable 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 years prior to study entry (other than non-melanoma skin cancer or in situ cervical cancer) or 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 consent/assent
  23. . Patient is unwilling or unable to adhere with study requirements and procedures
  24. . Currently receiving other experimental therapies

Locations

  • University of California San Francisco Benioff Children's Hospital
    San Francisco California 94158 United States
  • Lucile Packard Children's Hospital
    Palo Alto California 94304 United States

Lead Scientist at UCSF

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ID
NCT04862221
Phase
Phase 2
Study Type
Interventional
Last Updated