Hepatic Encephalopathy Clinical Trial
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
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.
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. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT01846806 -
The Role of Bacterial Overgrowth and Delayed Intestinal Transit in Hepatic Encephalopathy.
|
N/A | |
Completed |
NCT01559519 -
Post Transjugular Intrahepatic Portosystemic Shunt (Tips) Albumine Infusion to Prevent Hepatic Encephalopathy
|
Phase 4 | |
Recruiting |
NCT01178372 -
Secondary Prophylaxis of Hepatic Encephalopathy in Cirrhosis
|
Phase 4 | |
Completed |
NCT00914056 -
A Study of Controlled Lactulose Withdrawal
|
N/A | |
Completed |
NCT00740142 -
Efficacy of Combined Oral L-ornithine-L-aspartate and Lactulose in Patients With Hepatic Encephalopathy
|
Phase 4 | |
Completed |
NCT00558038 -
Safety and Efficacy of AST-120 Compared to Lactulose in Patients With Hepatic Encephalopathy
|
Phase 2 | |
Completed |
NCT00986895 -
A Study of Glyceryl Tri-(4-phenylbutyrate) Administered Orally as a Single Dose, and Twice Daily for Seven Consecutive Days to Subjects With Hepatic Impairment With Cirrhosis and to a Control Group
|
Phase 1 | |
Completed |
NCT00287235 -
Efficacy of Albumin Dialysis to Treat Patients With Hepatic Encephalopathy Using The Molecular Adsorbent Recirculating System (MARS)
|
N/A | |
Recruiting |
NCT05539027 -
Efficacy of L-Ornithine L-Aspartate (LOLA) as an Adjunct to Branched Chain Amino Acids (BCAA) Enriched Solutions on Clinical Outcomes in ICU Patients With Hepatic Encephalopathy
|
Phase 4 | |
Recruiting |
NCT04096014 -
Late Evening and Early Morning Protein Supplement to Reduce Readmissions for Hepatic Encephalopathy
|
N/A | |
Completed |
NCT05526404 -
Prevention of Hepatic Encephalopathy With Mobile Application Based Lactulose Titration
|
N/A | |
Completed |
NCT04082780 -
Rifamycin in Minimal Hepatic Encephalopathy
|
Phase 2 | |
Enrolling by invitation |
NCT06367127 -
Utility of the Clamping Bean Test (CBT) for Covert Hepatic Encephalopathy Screening
|
||
Active, not recruiting |
NCT05425316 -
Speech in Hepatic Encephalopathy (HE)
|
||
Recruiting |
NCT04415294 -
Flicker App for Minimal Hepatic Encephalopathy
|
||
Not yet recruiting |
NCT06072521 -
Efficacy of Lactoferrin as an Adjunct Therapy in Patients With Hepatic Encephalopathy
|
Phase 2 | |
Completed |
NCT02636647 -
Fecal Transplant in Recurrent Hepatic Encephalopathy
|
Phase 1 | |
Withdrawn |
NCT02086825 -
A Randomized Comparison of Rifaximin Versus Lactulose in Hospitalized Cirrhotic Patients With Renal Failure
|
Phase 3 | |
Completed |
NCT01446523 -
S. Endotoxin, Inflammatory Mediators and MRS Before and After Treatment in MHE
|
N/A | |
Completed |
NCT01218568 -
Rifaximin Plus Lactulose Versus Lactulose Alone for the Treatment of Hepatic Encephalopathy: a Double Blind Randomized Trial
|
N/A |