RECRUITING

TReatment for ImmUne Mediated PathopHysiology

Conditions

Acute Liver Failure Fulminant Hepatic Failure Hepatic Encephalopathy Acute Liver Injury Immune Dysregulation hepatic insufficiency liver diseases liver failure anti-thymocyte agents

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Quick Facts

Study Start:2022-02-09

Study Completion:2027-01-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04862221

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Year to 18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
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.	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

Inclusion Criteria

Exclusion Criteria

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.

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

Contacts and Locations

Study Contact

Katie Neighbors, MPH

CONTACT

312-227-4557

kneighbors@luriechildrens.org

Caitlin Schaffner, MPH

CONTACT

843-792-6588

schaffne@musc.edu

Principal Investigator

Estella M Alonso, MD

PRINCIPAL_INVESTIGATOR

Ann & Robert H Lurie Children's Hospital of Chicago

Valerie L Durkalski-Mauldin, PhD

PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Ed Doo, MD

STUDY_DIRECTOR

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

Averell Sherker, MD

STUDY_DIRECTOR

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

Study Locations (Sites)

Children's Hospital Los Angeles

Los Angeles, California, 90027

United States

Lucile Packard Children's Hospital

Palo Alto, California, 94304

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

Emory Children's Healthcare of Atlanta

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

Saint 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

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

Collaborators and Investigators

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

Estella M Alonso, MD, PRINCIPAL_INVESTIGATOR, Ann & Robert H Lurie Children's Hospital of Chicago
Valerie L Durkalski-Mauldin, PhD, PRINCIPAL_INVESTIGATOR, Medical University of South Carolina
Ed Doo, MD, STUDY_DIRECTOR, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Averell Sherker, MD, STUDY_DIRECTOR, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-02-09

Study Completion Date2027-01-31

Study Record Updates

Study Start Date2022-02-09

Study Completion Date2027-01-31

Terms related to this study

Keywords Provided by Researchers

hepatic insufficiency
liver diseases
liver failure
anti-thymocyte agents

Additional Relevant MeSH Terms

Acute Liver Failure
Fulminant Hepatic Failure
Hepatic Encephalopathy
Acute Liver Injury
Immune Dysregulation