Fulminant Hepatic FailurePhase 4NCT02375867
Steroids in Fulminant Hepatitis A in the Pediatric Age Group
A Phase 4 study testing prednisolone and methylprednisolone in people with Fulminant Hepatic Failure, run by National Liver Institute, Egypt at 1 site in Egypt.
Trial summary
Fulminant hepatic failure (FHF) in children is a potentially devastating disease. The mortality rate may reach 80-90% in the absence of liver transplantation. Liver injury is considered to be mainly immune mediated with augmentation of cytolytic pathways of infected hepatocytes. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Fulminant Hepatic Failure
- What is being tested?
- prednisolone and methylprednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteEgypt
- Study dates
- Jan 2015to Sep 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- The patient is diagnosed to have FHF, if he fulfilled all the following criteria:
- Evidence of liver dysfunction within 8 weeks of onset of symptoms (neonates may have only deranged liver functions without overt symptoms).
- Uncorrectable coagulopathy (6-8 hours after administration of one dose of parenteral vitamin K) with International Normalized Ratio (INR) >1.5 in patients with hepatic encephalopathy, or INR> 2.0 in patients without encephalopathy.
- No evidence of chronic liver disease.
Who cannot join
- 1. Presence of absolute contra-indications to steroid therapy (as presence of an active gastrointestinal bleeding, renal failure, acute pancreatitis, active tuberculosis, uncontrolled diabetes and psychosis).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety and Efficacy of Steroids in the Management of Fulminant Hepatic Failure Due to Hepatitis A Virus in the Pediatric Age Group
Fulminant hepatic failure (FHF) in children is a potentially devastating disease. The mortality rate may reach 80-90% in the absence of liver transplantation. Liver injury is considered to be mainly immune mediated with augmentation of cytolytic pathways of infected hepatocytes. For that, it is suggested that corticosteroids modulate the activity of the disease by suppressing the immune system.
Read the detailed description
Fulminant hepatic failure (FHF) in children is a potentially devastating disease. The mortality rate may reach 80-90% in the absence of liver transplantation. FHF is the clinical manifestation of liver cell death of a critical degree with insufficient hepatocellular regeneration and characterized by coagulopathy with or without hepatic encephalopathy.
Liver injury is considered to be mainly immune mediated with augmentation of cytolytic pathways of infected hepatocytes. For that, it was suggested that corticosteroids modulate the activity of the disease by suppressing the immune system.
- Conditions
- Fulminant Hepatic Failure
- Being tested
- prednisolone, methylprednisolone
- Medical subject headings
- Liver Failure, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
prednisoloneDrug
Also called Hostacortin-H
Oral administration of 1 mg/Kg/day
Also called Solumedrol
Intravenous injection of 0.8 mg/kg/day
| Study group | Role | What they receive |
|---|---|---|
| prednisolone | Active comparator | This group includes patients with FHF without encephalopathy Receives: Drug: prednisolone |
| methylprednisolone | Active comparator | This group includes patients with FHF with encephalopathy Receives: Drug: methylprednisolone |
| Non-intervention | No intervention | FHF patients without any of the proposed intervention as controls |
What is being measured
The primary outcome is the main question the study is designed to answer.
Side effect 1 Number of patients with anaphylaxis
Number of patients with anaphylaxis
Measured: 2 months
Side effect 2 Number of patients with angioedema
Number of patients with angioedema
Measured: 2 months
Side effect 3 Number of patients with cardiac arrest
Number of patients with cardiac arrest
Measured: 2 months
Side effect 4 Number of patients with arrhythmias
Number of patients with arrhythmias
Measured: 2 months
Side effect 5 Number of patients with circulatory collapse
Number of patients with circulatory collapse
Measured: 2 months
Side effect 6 Number of patients with congestive heart failure
Number of patients with congestive heart failure
Measured: 2 months
Side effect 7 Number of patients with pulmonary edema
Number of patients with pulmonary edema
Measured: 2 months
Side effect 8 Number of patients with pancreatitis
Number of patients with pancreatitis
Measured: 2 months
Secondary outcomes (5)
Efficacy 1 Number of survivors
number of living patients
Measured: 2 months
Efficacy 2 Number of deaths
number of died patients
Measured: 2 months
Efficacy 3 serum prothrombin time
serum prothrombin time
Measured: 72 hour
Efficacy 3 grade of encephalopathy
grade of encephalopathy
Measured: 72 hour
Efficacy 4 duration of encephalopathy
duration of encephalopathy
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2015 (estimated)
- Study startJan 2015
- Primary completionAug 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Fulminant Hepatic FailureStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Liver Institute, Egypt
- Sponsor type
- University, hospital or other
- Collaborators
- Quesna Central Hospital, Ministry Of Health, Egypt
- Responsible party
- Principal investigator, Mostafa M. Sira, National Liver Institute, Egypt
- Investigators
- Hanaa El-Araby, M.D., Principal investigator, Pediatric Hepatology Department, National Liver Institute, EgyptMostafa M Sira, M.D., Study director, Pediatric Hepatology Department, National Liver Institute, EgyptHaydi M Zakaria, M.Sc., Study chair, Quesna Central Hospital, Ministry Of Health, EgyptTahany A Salem, M.Sc., Study chair, Pediatric Hepatology Department, National Liver Institute, Egypt
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02375867
- Sponsor's protocol ID
- NLI-FHF-S-PED
- Status last verified
- Dec 2018
- First submitted
- 14 Feb 2015
- Last updated
- 17 Dec 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cochran JB, Losek JD. Acute liver failure in children. Pediatr Emerg Care. 2007 Feb;23(2):129-35. doi: 10.1097/PEC.0b013e3180308f4b.
PubMed 17351416Bernal W, Auzinger G, Dhawan A, Wendon J. Acute liver failure. Lancet. 2010 Jul 17;376(9736):190-201. doi: 10.1016/S0140-6736(10)60274-7.
PubMed 20638564Fujiwara K, Kojima H, Yasui S, Okitsu K, Yonemitsu Y, Omata M, Yokosuka O. Hepatitis A viral load in relation to severity of the infection. J Med Virol. 2011 Feb;83(2):201-7. doi: 10.1002/jmv.21958.
PubMed 21181913Fujiwara K, Yasui S, Yonemitsu Y, Fukai K, Arai M, Imazeki F, Suzuki A, Suzuki H, Sadahiro T, Oda S, Yokosuka O. Efficacy of combination therapy of antiviral and immunosuppressive drugs for the treatment of severe acute exacerbation of chronic hepatitis B. J Gastroenterol. 2008;43(9):711-9. doi: 10.1007/s00535-008-2222-5. Epub 2008 Sep 20.
PubMed 18807133Lahuna O, Rastegar M, Maiter D, Thissen JP, Lemaigre FP, Rousseau GG. Involvement of STAT5 (signal transducer and activator of transcription 5) and HNF-4 (hepatocyte nuclear factor 4) in the transcriptional control of the hnf6 gene by growth hormone. Mol Endocrinol. 2000 Feb;14(2):285-94. doi: 10.1210/mend.14.2.0423.
PubMed 10674400Seshadri R, Feldman BM, Ilowite N, Cawkwell G, Pachman LM. The role of aggressive corticosteroid therapy in patients with juvenile dermatomyositis: a propensity score analysis. Arthritis Rheum. 2008 Jul 15;59(7):989-95. doi: 10.1002/art.23829.
PubMed 18576304
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Steroids in the Management of Fulminant Hepatic Failure Due to Hepatitis A Virus in the Pediatric Age Group
- ClinicalTrials.gov ID
- NCT02375867
- Acronym / sponsor ID
- NLI-FHF-S-PED
- Conditions
- Fulminant Hepatic Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- National Liver Institute, EgyptUniversity, hospital or other
- Collaborators
- Quesna Central Hospital, Ministry Of Health, Egypt
- Study start
- Jan 2015 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 3 Mar 2015 (estimated)
- 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.
Fulminant hepatic failure (FHF) in children is a potentially devastating disease. The mortality rate may reach 80-90% in the absence of liver transplantation. Liver injury is considered to be mainly immune mediated with augmentation of cytolytic pathways of infected hepatocytes. For that, it is suggested that corticosteroids modulate the activity of the disease by suppressing the immune system.
Detailed description
Fulminant hepatic failure (FHF) in children is a potentially devastating disease. The mortality rate may reach 80-90% in the absence of liver transplantation. FHF is the clinical manifestation of liver cell death of a critical degree with insufficient hepatocellular regeneration and characterized by coagulopathy with or without hepatic encephalopathy.
Liver injury is considered to be mainly immune mediated with augmentation of cytolytic pathways of infected hepatocytes. For that, it was suggested that corticosteroids modulate the activity of the disease by suppressing the immune system.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| prednisolone | Active comparator | Drug: prednisoloneThis group includes patients with FHF without encephalopathy |
| methylprednisolone | Active comparator | Drug: methylprednisoloneThis group includes patients with FHF with encephalopathy |
| Non-intervention | No intervention | –FHF patients without any of the proposed intervention as controls |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Evidence of liver dysfunction within 8 weeks of onset of symptoms (neonates may have only deranged liver functions without overt symptoms).
- Uncorrectable coagulopathy (6-8 hours after administration of one dose of parenteral vitamin K) with International Normalized Ratio (INR) >1.5 in patients with hepatic encephalopathy, or INR> 2.0 in patients without encephalopathy.
- No evidence of chronic liver disease.
Key exclusion criteria (1 listed)
- 1. Presence of absolute contra-indications to steroid therapy (as presence of an active gastrointestinal bleeding, renal failure, acute pancreatitis, active tuberculosis, uncontrolled diabetes and psychosis).
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 |
|---|---|---|
| prednisoloneAlso: Hostacortin-HOral administration of 1 mg/Kg/day | Drug | prednisolone |
| methylprednisoloneAlso: SolumedrolIntravenous injection of 0.8 mg/kg/day | Drug | methylprednisolone |
Primary outcome
Side effect 1 Number of patients with anaphylaxis
Time frame: 2 months
Number of patients with anaphylaxis
Side effect 2 Number of patients with angioedema
Time frame: 2 months
Number of patients with angioedema
Side effect 3 Number of patients with cardiac arrest
Time frame: 2 months
Number of patients with cardiac arrest
Side effect 4 Number of patients with arrhythmias
Time frame: 2 months
Number of patients with arrhythmias
Side effect 5 Number of patients with circulatory collapse
Time frame: 2 months
Number of patients with circulatory collapse
Side effect 6 Number of patients with congestive heart failure
Time frame: 2 months
Number of patients with congestive heart failure
Side effect 7 Number of patients with pulmonary edema
Time frame: 2 months
Number of patients with pulmonary edema
Side effect 8 Number of patients with pancreatitis
Time frame: 2 months
Number of patients with pancreatitis
5 secondary outcomes
Efficacy 1 Number of survivors
Time frame: 2 months
Efficacy 2 Number of deaths
Time frame: 2 months
Efficacy 3 serum prothrombin time
Time frame: 72 hour
Efficacy 3 grade of encephalopathy
Time frame: 72 hour
Efficacy 4 duration of encephalopathy
Time frame: 2 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2018.
- Background: PubMed 17351416Cochran JB, Losek JD. Acute liver failure in children. Pediatr Emerg Care. 2007 Feb;23(2):129-35. doi: 10.1097/PEC.0b013e3180308f4b.
- Background: PubMed 20638564Bernal W, Auzinger G, Dhawan A, Wendon J. Acute liver failure. Lancet. 2010 Jul 17;376(9736):190-201. doi: 10.1016/S0140-6736(10)60274-7.
- Background: PubMed 21181913Fujiwara K, Kojima H, Yasui S, Okitsu K, Yonemitsu Y, Omata M, Yokosuka O. Hepatitis A viral load in relation to severity of the infection. J Med Virol. 2011 Feb;83(2):201-7. doi: 10.1002/jmv.21958.
- Background: PubMed 18807133Fujiwara K, Yasui S, Yonemitsu Y, Fukai K, Arai M, Imazeki F, Suzuki A, Suzuki H, Sadahiro T, Oda S, Yokosuka O. Efficacy of combination therapy of antiviral and immunosuppressive drugs for the treatment of severe acute exacerbation of chronic hepatitis B. J Gastroenterol. 2008;43(9):711-9. doi: 10.1007/s00535-008-2222-5. Epub 2008 Sep 20.
- Background: PubMed 10674400Lahuna O, Rastegar M, Maiter D, Thissen JP, Lemaigre FP, Rousseau GG. Involvement of STAT5 (signal transducer and activator of transcription 5) and HNF-4 (hepatocyte nuclear factor 4) in the transcriptional control of the hnf6 gene by growth hormone. Mol Endocrinol. 2000 Feb;14(2):285-94. doi: 10.1210/mend.14.2.0423.
- Background: PubMed 18576304Seshadri R, Feldman BM, Ilowite N, Cawkwell G, Pachman LM. The role of aggressive corticosteroid therapy in patients with juvenile dermatomyositis: a propensity score analysis. Arthritis Rheum. 2008 Jul 15;59(7):989-95. doi: 10.1002/art.23829.
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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.
Hanaa El-Araby, M.D. principal investigator
Pediatric Hepatology Department, National Liver Institute, Egypt
Mostafa M Sira, M.D. study director
Pediatric Hepatology Department, National Liver Institute, Egypt
Haydi M Zakaria, M.Sc. study chair
Quesna Central Hospital, Ministry Of Health, Egypt
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing prednisolone and methylprednisolone in people with Fulminant Hepatic Failure, run by National Liver Institute, Egypt at 1 site in Egypt.
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 1 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: finished, as of the sponsor's last update on 17 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Side effect 1 Number of patients with anaphylaxis (time frame: 2 months). The study lists 8 primary outcomes in all. 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 NCT02375867, which also lists 6 linked publications.
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 17 Dec 2018.