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 (LT) in an additional 20-30%. In the majority of cases, a specific cause of the liver injury is never determined. Recent research conducted in these patients supports the theory that many of these patients have liver injury related to a hyperinflammatory immune response to everyday infections or environmental exposures. Studies have recently implicated t lymphocytes as the central drivers of the inflammatory process. Physicians caring for palf patients are searching for therapies that quiet this t cell response, dampen the inflammatory cascade and allow the patient's remaining liver cells to heal and regenerate. Clinical experience in children with abnormal hyperinflammatory immune responses associated with other disease states such as systemic juvenile idiopathic arthritis and acquired aplastic anemia has demonstrated that both high dose corticosteroids and equine anti- thymocyte globulin can suppress immune responses and reverse progressive tissue damage. The goal of the pediatric acute liver failure immune response network (palf IRN) is to support a treatment trial of immunosuppressive therapy using high dose corticosteroids or equine anti-thymocyte globulin to reverse harmful inflammatory immune responses in children with palf to prevent further disease progression and reduce mortality and LT in this population. We propose the treatment for immune mediated pathophysiology (triumph) trial, a double-blind, three arm, randomized, placebo controlled trial of high dose methylprednisolone or equine anti-thymocyte globulin. We will test the hypothesis that survival with native liver at 21 days post randomization will be significantly higher in patients receiving immunosuppressive therapy as compared to patients that receive supportive care alone. We will also determine the safety of immunosuppressive therapy in palf patients and define the balance between risk of side-effects and treatment benefit. Our outcomes will include not only clinical end-points such as patient survival, time to resolution of disease and adverse health events, but also measures of patient reported outcomes during rehabilitation from the illness. Trial participants will provide blood and liver samples that will be examined to better understand their immune responses, especially that of t lymphocytes, in both the circulation and in the liver. Samples will be stored in a repository to support future studies exploring new aspects of this rare disease.
Trustees Of Indiana UniversityDr.JeanMollestonwillparticipateastheIndianaUniversityPI forthegrantproposalentitled"PediatricAcuteLiverfailure…
$67,155
Subrecipient not on record
Dr.ShikhaSundaramwillparticipateastheUniversityofColoradoDenverPI forthegrantproposalentitled"PediatricAcute…
$169,097
The Children's Hospital Of PhiladelphiaCHOP’sClinical ImmunologyLabwillserveastheBiomarkerCoreLabforTRIUMPH.Dr.Behrens, aRheumatologist, willserveasChairoftheMechanistic…
$2,857,580
The Washington UniversityDr.DavidRudnickwillparticipateastheWashingtonUniversityPIforthegrantproposalentitled"Pediatric…
The Children's Hospital Of PhiladelphiaCHOP’s Clinical Immunology Lab will serve as the Biomarker Core Lab for TRIUMPH. Dr. Behrens, a Rheumatologist, will serve as Chair of the Mechanistic…
$1,752,605
Seattle Children's HospitalDr. Evelyn Hsu will participate as the Seattle Children's Research Institute Site PI for the grant proposal entitled "Pediatric Acute Liver failure Immune…
$335,677
Seattle Children's HospitalDr. Ada Kong is the manager of Seattle Children’s Investigational Drug Service (IDS). She and her team will provide the following services for Dr. Estella…
$199,618
Georgetown UniversityDr. Udeme Ekong will participate as the independent Medical Safety Monitor for the grant proposal entitled "Pediatric Acute Liver failure Immune Response…
$183,980
The University Of Texas Southwestern Medical CenterDr. Norberto Rodriguez-Baez will participate as the University of Texas Southwestern Medical Center Dallas, Texas site PI for the grant proposal entitled…
$142,096
Subrecipient not on record
Dr. Philip Rosenthal will participate as the UCSF PI for the grant proposal entitled "Pediatric Acute Liver failure Immune Response Network: TReatment for…
$190,084
University Of UtahDr. Kyle Jensen will participate as the University of Utah PI for the grant proposal entitled "Pediatric Acute Liver failure Immune Response Network:…
$159,279
Subrecipient not on record
Dr. Shikha Sundaram will participate as the University of Colorado Denver PI for the grant proposal entitled "Pediatric Acute Liver failure Immune Response…
Subrecipient not on record
Dr. Jaime Chu, MD will participate as the Mount Sinai RMTI PI for the grant proposal entitled "Pediatric Acute Liver failure Immune Response Network:…
The Washington UniversityDr. David Rudnick will participate as the Washington University PI for the grant proposal entitled "Pediatric Acute Liver failure Immune Response Network:…
$154,305
Children's Hospital LOS AngelesDr. Beth A. Carter will participate as the Children’s Hospital Los Angeles PI for the grant proposal entitled "Pediatric Acute Liver failure Immune Response…
$169,331
Baylor College Of MedicineDr. Anna Banc-Husu will participate as the Baylor College of Medicine Site PI for the grant proposal entitled "Pediatric Acute Liver failure Immune Response…
$207,536
Childrens Mercy HospitalDr. Ryan Fischer will participate as the The Children’s Mercy Hospital PI for the grant proposal entitled "Pediatric Acute Liver failure Immune Response…
$160,193
The Children's Hospital CorporationDr. Scott Elisofon will participate as the Boston Children’s Hospital PI for the grant proposal entitled "Pediatric Acute Liver failure Immune Response Network:…
$187,514
Trustees Of Indiana UniversityDr. Jean Molleston will participate as the Indiana University PI for the grant proposal entitled "Pediatric Acute Liver failure Immune Response Network:…
$161,902
Seattle Children's HospitalDr. Ada Kong is the manager of Seattle Children’s Investigational Drug Service (IDS). She and her team will provide the following services for Dr. Estella…
$167,268
Georgetown University (The)Dr. Udeme Ekong will participate as the independent Medical Safety Monitor for the grant proposal entitled "Pediatric Acute Liver failure Immune Response…
$142,556
The Medical University Of South CarolinaDATA COORDINATION UNIT SCOPE OF WORK The Data Coordination Unit at the Medical University of South Carolina will serve as the Statistical and Data…
$1,852,406
Trustees Of Indiana UniversityPediatric Acute Liver Failure Immune Response Network Treatment for Immune Mediated Pathophysiology (PALF IRN TRIUMPH)
U01DK127995 was awarded to ANN & Robert H Lurie Childrens Hospital Of Chicago by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on June 15, 2021.
How much is award U01DK127995 worth?
$30,880,746 has been obligated on U01DK127995: $27,216,328 in federal funding and $3,664,418 in non-federal funding.
ANN & Robert H Lurie Childrens Hospital Of Chicago UEI XJ7MMPHBMGM7
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health, Department of Health and Human Services