Clinical trial NCT02375867: Steroids in Fulminant Hepatitis A in the Pediatric Age Group
Official title: Safety and Efficacy of Steroids in the Management of Fulminant Hepatic Failure Due to Hepatitis A Virus in the Pediatric Age Group
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fulminant Hepatic Failure
Lead sponsor: National Liver Institute, Egypt
Sponsor class: OTHER
Collaborators: name: Quesna Central Hospital, Ministry Of Health, Egypt
First posted: 2015-03-03
Enrollment: 33
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

The patient is diagnosed to have FHF, if he fulfilled all the following criteria:

1. Evidence of liver dysfunction within 8 weeks of onset of symptoms (neonates may have only deranged liver functions without overt symptoms).
2. 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.
3. No evidence of chronic liver disease.

Exclusion Criteria:

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).

Primary outcomes:
measure: Side effect 1 Number of patients with anaphylaxis
timeFrame: 2 months
measure: Side effect 2 Number of patients with angioedema
timeFrame: 2 months
measure: Side effect 3 Number of patients with cardiac arrest
timeFrame: 2 months
measure: Side effect 4 Number of patients with arrhythmias
timeFrame: 2 months
measure: Side effect 5 Number of patients with circulatory collapse
timeFrame: 2 months
measure: Side effect 6 Number of patients with congestive heart failure
timeFrame: 2 months
measure: Side effect 7 Number of patients with pulmonary edema
timeFrame: 2 months
measure: Side effect 8 Number of patients with pancreatitis
timeFrame: 2 months
Secondary outcomes:
measure: Efficacy 1 Number of survivors
timeFrame: 2 months
measure: Efficacy 2 Number of deaths
timeFrame: 2 months
measure: Efficacy 3 serum prothrombin time
timeFrame: 72 hour
measure: Efficacy 3 grade of encephalopathy
timeFrame: 72 hour
measure: Efficacy 4 duration of encephalopathy
timeFrame: 2 months
Other outcomes:
Locations:
city: Menoufia
country: Egypt
facility: National Liver Institute
Study officials:
affiliation: Pediatric Hepatology Department, National Liver Institute, Egypt
name: Hanaa El-Araby, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Pediatric Hepatology Department, National Liver Institute, Egypt
name: Mostafa M Sira, M.D.
role: STUDY_DIRECTOR
affiliation: Quesna Central Hospital, Ministry Of Health, Egypt
name: Haydi M Zakaria, M.Sc.
role: STUDY_CHAIR
affiliation: Pediatric Hepatology Department, National Liver Institute, Egypt
name: Tahany A Salem, M.Sc.
role: STUDY_CHAIR
References:
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citation: Bernal 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.
citation: Fujiwara 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.
citation: Fujiwara 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.
citation: Lahuna 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.
citation: Seshadri 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.