Acute Liver FailurePhase 2TRIUMPHNCT04862221
TReatment for ImmUne Mediated PathopHysiology
A Phase 2 study testing High-dose methylprednisolone, Equine anti-thymocyte globulin and Prednisolone in people with Acute Liver Failure and Fulminant Hepatic Failure, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 17 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Acute Liver Failure, Fulminant Hepatic Failure, Hepatic Encephalopathy
- What is being tested?
- High-dose methylprednisolone, Equine anti-thymocyte globulin and Prednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 17 sitesUnited States
- Study dates
- 9 Feb 2022to Feb 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patient with liver injury of ≤ 6 weeks duration resulting in an international normalization ratio (INR) of ≥ 1.5 or < 2.0 (not corrected by vitamin K) with evidence of hepatic encephalopathy (HE), INR of ≥ 1.5 or < 2.0 for at least 7 days duration without evidence of HE or INR ≥ 2.0 without evidence of HE.
- Age is greater than or equal to 1 year and less than 18 years of age.
- 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.
- Females of reproductive potential should not plan on conceiving children during the study and must agree to use a medically accepted form of contraception.
Who cannot join
- Evidence of active infection with Hepatitis A, B, C, E or evidence of acute herpes simplex virus (HSV) or adenovirus infection
- Travel within the past 3 months to an area highly endemic for Hepatitis E
- 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.
- Aplastic anemia as defined by standardized criteria [1] diagnosed prior to enrollment
- Diagnosis of autoimmune Hepatitis (AIH)
- Diagnosis of acute Wilson disease
Show all 24Show fewer
- Diagnosis of inborn error of metabolism Note: Suspicion of metabolic disease is not an exclusion for entry into the Trial.
- Diagnosis of acute drug or toxin-induced liver injury
- History of recreational drug use within the past 4 weeks
- Therapy with an immunosuppressive agent, including chemotherapy, biological therapies or an experimental drug or device within the past 6 weeks
- Liver injury due to ischemia
- Liver dysfunction diagnosed more than 6 weeks prior to screening
- History of allergy to horse dander
- Sepsis
- 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
- Solid organ or stem cell transplant recipient
- Pregnant or breast-feeding at the time of proposed study entry
- Clinical AIDS or HIV positive
- 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
- Received a live-virus vaccine within 4 weeks of study entry
- Patients with positive respiratory secretion testing for respiratory viral infection including SARS-CoV-2, influenza and respiratory syncytial virus only if they also have declining respiratory function
- Psychiatric or addictive disorders that would preclude obtaining informed consent/assent
- Patient is unwilling or unable to adhere with study requirements and procedures
- Currently receiving other experimental therapies
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Children's Hospital Boston
Boston, Massachusetts, 02115
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
UT Southwestern Medical Center Children's Health
Dallas, Texas, 75235
Texas Children's Hospital
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
The Children's Mercy Hospital
Kansas City, Missouri, 64108
Children's Hospital Los Angeles
Los Angeles, California, 90027
Children's Hospital Vanderbilt
Nashville, Tennessee, 37232
NYP Morgan Stanley Children's Hospital
New York, New York, 10032
Lucile Packard Children's Hospital
Palo Alto, California, 94304
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Rady Children's Hospital
San Diego, California, 92123
Seattle Children's Hospital
Seattle, Washington, 98105
St. Louis Children's Hospital
St Louis, Missouri, 63110
About this study
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.
Read the detailed description
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.
This study includes a prospective observational cohort study of up to 50 patients with PALF who meet the randomized controlled trial (RCT) eligibility criteria and are willing to provide longitudinal observational data.
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.
Recruitment into the randomized controlled trial stopped on February 17, 2026, but recruitment into the observational cohort will continue for about 6 months.
- Conditions
- Acute Liver Failure, Fulminant Hepatic Failure, Hepatic Encephalopathy, Acute Liver Injury, Immune Dysregulation
- Being tested
- High-dose methylprednisolone, Equine anti-thymocyte globulin, Prednisolone, Placebo for prednisolone, Placebo for infusions
- Keywords
- hepatic insufficiency, liver diseases, liver failure, anti-thymocyte agents
- Medical subject headings
- Liver Failure, Acute, Hepatic Encephalopathy, Hepatic Insufficiency, Liver Diseases, Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-dose methylprednisoloneDrug
Also called Solu-Medrol
Subjects in the high-dose methylprednisolone arm will receive an initial dose of methylprednisolone IV 10 mg/kg/day for 3 days and 5 mg/kg/day on Day 4. Normal saline will be used as placebo pre-medications and infusions given at the same volume and duration as the eATG infusions.
Equine anti-thymocyte globulinDrug
Also called ATGAM
Subjects will receive eATG IV 40 mg/kg/day on Days 1- 4. Day 1 eATG infusion is run over 8 hours and Day 2-4 infusions are run over 4 hours.
PrednisoloneDrug
Also called 15 mg/mL oral solution National Drug Code: 0121-0885-08
Subjects will receive prednisolone 1 mg/kg on Days 5-13 followed by a gradual taper with discontinuation at 42 Days as indicated below.
Days 5 - 13 Prednisolone PO 1 mg/kg/day (max 50 mg/day)
Days 14- 20 Prednisolone PO 0.5 mg/kg/day (max 25 mg/day)
Days 21 - 27 Prednisolone PO 0.3 mg/kg/day (max 15 mg/day)
Days 28 - 34 Prednisolone PO 0.1 mg/kg/day (max 5 mg/day)
Days 35 - 41 Prednisolone PO 0.1 mg/kg every OTHER day (max 5 mg every other day)
Day 42 Discontinue
Placebo for prednisoloneDrug
Subjects will receive 1 mg/kg/day of oral placebo for prednisolone on days 5-13 followed by a gradual taper to discontinuation at 42 days as indicated below. Subjects receiving oral placebo will be given a solution that closely resembles the treatment drug.
Days 5 - 13 Placebo for Prednisolone PO 1 mg/kg/day (max 50 mg/day)
Days 14- 20 Placebo for Prednisolone PO 0.5 mg/kg/day (max 25 mg/day)
Days 21 - 27 Placebo for Prednisolone PO 0.3 mg/kg/day (max 15 mg/day)
Days 28 - 34 Placebo for Prednisolone PO 0.1 mg/kg/day (max 5 mg/day)
Days 35 - 41 Placebo for Prednisolone PO 0.1 mg/kg every OTHER day (max 5 mg every other day)
Day 42 Discontinue
Placebo for infusionsDrug
Also called 0.9% Sodium chloride
Subjects randomized to the supportive care alone arm will receive normal saline in place of all study treatments (skin test, premedication and IV infusions) on Days 1-4 given at the same volume and duration as the eATG infusions.
DiphenhydramineDrug
Also called Benadryl
Subjects in the eATG arm will receive pre-treatment medication diphenhydramine IV 1 mg/kg prior to start of eATG infusion.
Also called Solu-Medrol
Subjects in the eATG arm will receive pre-treatment medication methylprednisolone IV 1 mg/kg prior to start of eATG infusion.
| Study group | Role | What they receive |
|---|---|---|
| High-dose methylprednisolone | Experimental | Intravenous methylprednisolone at an initial dose of 10 mg/kg/day for 3 days, 5 mg/kg/day on day 4. Receives: Drug: High-dose methylprednisolone; Drug: Prednisolone |
| Equine anti-thymocyte globulin | Experimental | Intravenous equine anti-thymocyte globulin at a dose of 40 mg/kg/day for 4 days. Receives: Drug: Equine anti-thymocyte globulin; Drug: Prednisolone; Drug: Diphenhydramine; Drug: Methylprednisolone |
| Supportive care | Placebo comparator | Supportive care will be administered as determined by the clinical team at participating clinical sites in accordance with their local practices and standards. Receives: Drug: Placebo for prednisolone; Drug: Placebo for infusions |
| Observational Cohort | No intervention | This study includes a prospective observational cohort study of patients with Pediatric Acute Liver Failure who meet the randomized controlled trial eligibility criteria and are willing to provide longitudinal observational data. Patients who provide consent will receive the enrolling institution's standard of care and will be followed for up to 90-days for clinical (observational) assessments and biospecimen collection for the biorepository. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival with native liver (SNL)
Alive and without a liver transplant 21 days following randomization
Measured: 21 days
Secondary outcomes (1)
Survival with native liver (SNL)
Alive and without a liver transplant 6 months (180 days) following randomization
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2021
- Study start9 Feb 2022
- Primary completion3 Aug 2026
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Liver FailureStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Ann & Robert H Lurie Children's Hospital of Chicago
- Responsible party
- Sponsor
- Investigators
- Estella M Alonso, MD, Principal investigator, Ann & Robert H Lurie Children's Hospital of ChicagoValerie L Durkalski-Mauldin, PhD, Principal investigator, Medical University of South CarolinaEd 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)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04862221
- Sponsor's protocol ID
- PALF IRN/TRIUMPH
- Other IDs
- U01DK062436
- Acronym
- TRIUMPH
- Status last verified
- Aug 2026
- First submitted
- 23 Apr 2021
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be available at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repository. The public use dataset, along with the study protocol, the data dictionary, annotated case report forms and a brief set of instructions ("Readme" file) will be provided.
Publications
Chapin CA, Squires JE, Horslen SP, Alonso EM. Equipoise in pediatric acute liver failure. J Pediatr Gastroenterol Nutr. 2024 May;78(5):1001-1004. doi: 10.1002/jpn3.12166. Epub 2024 Feb 26. No abstract available.
PubMed 38409886
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04862221
- Acronym / sponsor ID
- TRIUMPH / PALF IRN/TRIUMPH
- Conditions
- Acute Liver Failure, Fulminant Hepatic Failure, Hepatic Encephalopathy, Acute Liver Injury, Immune Dysregulation
- Keywords
- hepatic insufficiency, liver diseases, liver failure, anti-thymocyte agents
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 44 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Collaborators
- Ann & Robert H Lurie Children's Hospital of Chicago
- Study start
- 9 Feb 2022 (actual)
- Primary completion
- 3 Aug 2026 (actual)
- Study completion
- Feb 2027 (estimated)
- First posted
- 27 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
This study includes a prospective observational cohort study of up to 50 patients with PALF who meet the randomized controlled trial (RCT) eligibility criteria and are willing to provide longitudinal observational data.
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.
Recruitment into the randomized controlled trial stopped on February 17, 2026, but recruitment into the observational cohort will continue for about 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| High-dose methylprednisolone | Experimental | Drug: High-dose methylprednisolone, Drug: PrednisoloneIntravenous methylprednisolone at an initial dose of 10 mg/kg/day for 3 days, 5 mg/kg/day on day 4. |
| Equine anti-thymocyte globulin | Experimental | Drug: Equine anti-thymocyte globulin, Drug: Prednisolone, Drug: Diphenhydramine, Drug: MethylprednisoloneIntravenous equine anti-thymocyte globulin at a dose of 40 mg/kg/day for 4 days. |
| Supportive care | Placebo comparator | Drug: Placebo for prednisolone, Drug: Placebo for infusionsSupportive care will be administered as determined by the clinical team at participating clinical sites in accordance with their local practices and standards. |
| Observational Cohort | No intervention | –This study includes a prospective observational cohort study of patients with Pediatric Acute Liver Failure who meet the randomized controlled trial eligibility criteria and are willing to provide longitudinal observational data. Patients who provide consent will receive the enrolling institution's standard of care and will be followed for up to 90-days for clinical (observational) assessments and biospecimen collection for the biorepository. |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Patient with liver injury of ≤ 6 weeks duration resulting in an international normalization ratio (INR) of ≥ 1.5 or < 2.0 (not corrected by vitamin K) with evidence of hepatic encephalopathy (HE), INR of ≥ 1.5 or < 2.0 for at least 7 days duration without evidence of HE or INR ≥ 2.0 without evidence of HE.
- Age is greater than or equal to 1 year and less than 18 years of age.
- 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.
- Females of reproductive potential should not plan on conceiving children during the study and must agree to use a medically accepted form of contraception.
Key exclusion criteria (24 listed)
- Evidence of active infection with Hepatitis A, B, C, E or evidence of acute herpes simplex virus (HSV) or adenovirus infection
- Travel within the past 3 months to an area highly endemic for Hepatitis E
- 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.
- Aplastic anemia as defined by standardized criteria [1] diagnosed prior to enrollment
- Diagnosis of autoimmune Hepatitis (AIH)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High-dose methylprednisoloneAlso: Solu-MedrolSubjects in the high-dose methylprednisolone arm will receive an initial dose of methylprednisolone IV 10 mg/kg/day for 3 days and 5 mg/kg/day on Day 4. Normal saline will be used as placebo pre-medications and infusions given at the same volume and duration as the eATG infusions. | Drug | High-dose methylprednisolone |
| Equine anti-thymocyte globulinAlso: ATGAMSubjects will receive eATG IV 40 mg/kg/day on Days 1- 4. Day 1 eATG infusion is run over 8 hours and Day 2-4 infusions are run over 4 hours. | Drug | Equine anti-thymocyte globulin |
| PrednisoloneAlso: 15 mg/mL oral solution National Drug Code: 0121-0885-08Subjects will receive prednisolone 1 mg/kg on Days 5-13 followed by a gradual taper with discontinuation at 42 Days as indicated below. Days 5 - 13 Prednisolone PO 1 mg/kg/day (max 50 mg/day) Days 14- 20 Prednisolone PO 0.5 mg/kg/day (max 25 mg/day) Days 21 - 27 Prednisolone PO 0.3 mg/kg/day (max 15 mg/day) Days 28 - 34 Prednisolone PO 0.1 mg/kg/day (max 5 mg/day) Days 35 - 41 Prednisolone PO 0.1 mg/kg every OTHER day (max 5 mg every other day) Day 42 Discontinue | Drug | Equine anti-thymocyte globulin, High-dose methylprednisolone |
| Placebo for prednisoloneSubjects will receive 1 mg/kg/day of oral placebo for prednisolone on days 5-13 followed by a gradual taper to discontinuation at 42 days as indicated below. Subjects receiving oral placebo will be given a solution that closely resembles the treatment drug. Days 5 - 13 Placebo for Prednisolone PO 1 mg/kg/day (max 50 mg/day) Days 14- 20 Placebo for Prednisolone PO 0.5 mg/kg/day (max 25 mg/day) Days 21 - 27 Placebo for Prednisolone PO 0.3 mg/kg/day (max 15 mg/day) Days 28 - 34 Placebo for Prednisolone PO 0.1 mg/kg/day (max 5 mg/day) Days 35 - 41 Placebo for Prednisolone PO 0.1 mg/kg every OTHER day (max 5 mg every other day) Day 42 Discontinue | Drug | Supportive care |
| Placebo for infusionsAlso: 0.9% Sodium chlorideSubjects randomized to the supportive care alone arm will receive normal saline in place of all study treatments (skin test, premedication and IV infusions) on Days 1-4 given at the same volume and duration as the eATG infusions. | Drug | Supportive care |
| DiphenhydramineAlso: BenadrylSubjects in the eATG arm will receive pre-treatment medication diphenhydramine IV 1 mg/kg prior to start of eATG infusion. | Drug | Equine anti-thymocyte globulin |
| MethylprednisoloneAlso: Solu-MedrolSubjects in the eATG arm will receive pre-treatment medication methylprednisolone IV 1 mg/kg prior to start of eATG infusion. | Drug | Equine anti-thymocyte globulin |
Primary outcome
Survival with native liver (SNL)
Time frame: 21 days
Alive and without a liver transplant 21 days following randomization
1 secondary outcome
Survival with native liver (SNL)
Time frame: 180 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Derived from this study: PubMed 38409886Chapin CA, Squires JE, Horslen SP, Alonso EM. Equipoise in pediatric acute liver failure. J Pediatr Gastroenterol Nutr. 2024 May;78(5):1001-1004. doi: 10.1002/jpn3.12166. Epub 2024 Feb 26. No abstract available.
- Individual participant dataSharing planned: Yes. Data will be available at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repository. The public use dataset, along with the study protocol, the data dictionary, annotated case report forms and a brief set of instructions ("Readme" file) will be provided.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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)
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing High-dose methylprednisolone, Equine anti-thymocyte globulin and Prednisolone in people with Acute Liver Failure and Fulminant Hepatic Failure, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 17 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival with native liver (SNL) (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04862221, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.