- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02651350
Efficacy and Safety of Glucocorticosteroid Treatment in the Patients With Chronic Recurrent DILI
August 7, 2020 updated by: Beijing 302 Hospital
A Randomized Controlled Clinical Trial on the Efficacy and Safety of Glucocorticosteroid in the Patients With Chronic Recurrent Drug-induced Liver Injury
This study is to observe the efficacy and safety of glucocorticosteroid treatment in the patients with chronic recurrent drug-induced liver injury (DILI).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Drug-induced liver injury (DILI) refers to liver diseases caused by drugs and toxic substances.
DILI is a clinical event that can be associated with severe outcomes such as acute liver failure.
Up to now, approximately 1000 drugs, herbal products, vitamins and illicit compounds are associated with liver injury.
Recently, the incidence of DILI is rising.
In our hospital, hospitalized patients with DILI was increased from 1.39% in 2002 to 2.31% in 2006, and further up to 3.17% in 2011, which indicated 2.3-folds increase over last ten years.15% to 20% patients with acute DILI are prone to chronic liver disease.
For patients with chronic recurrent DILI, routine liver protective treatment was difficult to rescue abnormal liver functions.
Moreover, increasing health care costs seriously affect the patient's quality of life.
Glucocorticosteroids can inhibit the non-specific inflammation and permeability of the capillary bile duct, limit the activation of T lymphocytes, and selectively inhibit B lymphocytes to produce antibodies, thus preventing or delaying the immune-induced liver injury.
Glucocorticoid treatment of severe DILI has accepted some recognition, but the effect of repeated episodes of chronic DILI, due to a lack of randomized controlled studies, is still unclear.
Therefore, we shall design two groups on the basis of the ratio of 1:1, namely, glucocorticoid treatment group and standard treatment alone group.
Participants in glucocorticoid treatment group will receive methylprednisolone,48mg/d for the 1st week, 32mg/d for the 2nd week, 24mg/d for the next two weeks, followed by 16mg/d for 32 weeks and reduction in doses of methylprednisolone by 4 mg per 4 weeks until drug withdrawal.
Participants in glucocorticoid treatment group also receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA) in the first 12 weeks.
Participants in standard treatment group will only receive treatment by routine liver protection drugs including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA) in the first 12 weeks.The efficacy and safety of glucocorticoid treatment in the patients with chronic recurrent DILI will be observed during the treatment and follow-up period.
Study Type
Interventional
Enrollment (Actual)
80
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Beijing
-
Beijing, Beijing, China, 100039
- Beijing 302 hospital,China
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 58 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Meet with ACG clinic guidelines for diagnostic criteria of chronic DILI;
Meet any of the following conditions:
- serum AST or ALT ≥ 10 fold ULN;
- serum AST or ALT ≥ 5 fold ULN and TBIL ≥ 2 fold ULN;
- liver histology indicates bridging necrosis or multiacinar necrosis or moderate or more inflammation or inflammation G3 or more;
- Women of childbearing age had a negative urine pregnancy test, and the subjects are willing to have no family planning during the study and to take effective measures;
- Voluntary participation, understanding and signing of informed consent, comply with the requirements of the research;
Exclusion Criteria:
- Patients with serious pre-existent comorbid conditions (vertebral compression fractures,psychosis,active peptic ulcer, brittle diabetes,uncontrolled hypertension;
- Patients with intolerances to prednisone;
- Patients with severe infection receiving antibiotics, anti-fungal,anti-viral therapy;
- Viral hepatitis,alcoholic or non-alcoholic liver disease,Wilson's disease or other inherited metabolic liver diseases.
- Pregnancy or desire of pregnancy;
- Breast-feeding;
- Liver cancer or other malignant tumor;
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Methylprednisolone
Participants will receive methylprednisolone from week 0 through week 48 study visit in combination with standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA) in the first 12 weeks.
Participants will then be followed until week 72 study visit.
|
Participants will receive methylprednisolone,48mg/d for the 1st week,32mg/d for the 2nd week,24mg/d for the next two weeks, followed by 16mg/d for 32 weeks and reduction in doses of methylprednisolone by 4 mg per 4 weeks until drug withdrawal.Participants will also receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA) in the first 12 weeks.The total treatment duration will be 48 weeks.
Follow-up duration is 24 weeks.
Other Names:
Participants will only receive standard treatment,namely,routine liver protection drugs including reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA) from week 0 through week 12 study visit.
Participants will then be followed until week 72.
Other Names:
|
Active Comparator: Standard Treatment
Participants will only receive standard treatment (namely,routine liver protection drugs) including reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA) from week 0 through week 12 study visit.
Participants will then be followed until week 72 study visit.
|
Participants will only receive standard treatment,namely,routine liver protection drugs including reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA) from week 0 through week 12 study visit.
Participants will then be followed until week 72.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The relapse or recurrent rate of illness, namely, appearance of obviously abnormal liver function again during treatment and follow-up period
Time Frame: At week 24
|
The biochemical relapse rate was analyzed by either intention to treat (ITT) or per protocol set (PPS).
Biochemical relapse was characterized either by the serum alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥ 3 × upper limits of normal (ULN) or alkaline phosphatase (ALP) ≥ 2 × ULN, or by at least 2 folds increase in serum ALT or AST or ALP from the abnormal index lately.
|
At week 24
|
The relapse or recurrent rate of illness, namely, appearance of obviously abnormal liver function again during treatment and follow-up period
Time Frame: At week 72
|
The biochemical relapse rate was analyzed by either intention to treat (ITT) or per protocol set (PPS).
Biochemical relapse was characterized either by the serum alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥ 3 × upper limits of normal (ULN) or alkaline phosphatase (ALP) ≥ 2 × ULN, or by at least 2 folds increase in serum ALT or AST or ALP from the abnormal index lately.
|
At week 72
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Days of normalization of liver functions including serum levels of ALT, AST, TBIL,GGT and ALP.
Time Frame: From week 1 to week 12
|
The normalization time(days) of biochemistry was defined as the days of normalization of each biochemical parameter (ALT, AST, TBil, ALP and gamma-glutamyl transpeptidase), respectively.
|
From week 1 to week 12
|
The liver histological changes between two liver biopsies
Time Frame: At week 0 and at week 48 week
|
Histological improvement was defined as at least two points reduce in the activity score, or at least one point decrease in the fibrosis score in accordance to Ishak scoring system.
|
At week 0 and at week 48 week
|
The number of participants with methylprednisolone treatment-related adverse events, such as severe osteopenia, uncontrolled hypertension
Time Frame: At week 24 and at week 72
|
The adverse effects in each group were evaluated according to the Common Terminology Criteria for Adverse Events (version 5.0).
The types of steroid-related adverse effects referred to the EASL/AASLD autoimmune hepatitis Guidelines.
Adverse effects occurred in both the treatment period and the follow-up period were combined to evaluate.
|
At week 24 and at week 72
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Chalasani NP, Hayashi PH, Bonkovsky HL, Navarro VJ, Lee WM, Fontana RJ; Practice Parameters Committee of the American College of Gastroenterology. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014 Jul;109(7):950-66; quiz 967. doi: 10.1038/ajg.2014.131. Epub 2014 Jun 17.
- Moreno L, Sanchez-Delgado J, Vergara M, Casas M, Miquel M, Dalmau B. Recurrent drug-induced liver injury (DILI) with ciprofloxacin and amoxicillin/clavulanic. Rev Esp Enferm Dig. 2015 Dec;107(12):767-8. doi: 10.17235/reed.2015.3810/2015.
- Tencate V, Komorowski R, Cronin D, Hong J, Gawrieh S. A case study: refractory recurrent autoimmune hepatitis following liver transplantation in two male patients. Transplant Proc. 2014 Jan-Feb;46(1):298-300. doi: 10.1016/j.transproceed.2013.09.028.
- Lucena MI, Kaplowitz N, Hallal H, Castiella A, Garcia-Bengoechea M, Otazua P, Berenguer M, Fernandez MC, Planas R, Andrade RJ. Recurrent drug-induced liver injury (DILI) with different drugs in the Spanish Registry: the dilemma of the relationship to autoimmune hepatitis. J Hepatol. 2011 Oct;55(4):820-7. doi: 10.1016/j.jhep.2010.12.041. Epub 2011 Feb 19.
- Suzuki A, Brunt EM, Kleiner DE, Miquel R, Smyrk TC, Andrade RJ, Lucena MI, Castiella A, Lindor K, Bjornsson E. The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury. Hepatology. 2011 Sep 2;54(3):931-9. doi: 10.1002/hep.24481. Epub 2011 Aug 8.
- Weiler-Normann C, Schramm C. Drug induced liver injury and its relationship to autoimmune hepatitis. J Hepatol. 2011 Oct;55(4):747-9. doi: 10.1016/j.jhep.2011.02.024. Epub 2011 Mar 9. No abstract available.
- Bessone F, Lucena MI, Roma MG, Stephens C, Medina-Caliz I, Frider B, Tsariktsian G, Hernandez N, Bruguera M, Gualano G, Fassio E, Montero J, Reggiardo MV, Ferretti S, Colombato L, Tanno F, Ferrer J, Zeno L, Tanno H, Andrade RJ. Cyproterone acetate induces a wide spectrum of acute liver damage including corticosteroid-responsive hepatitis: report of 22 cases. Liver Int. 2016 Feb;36(2):302-10. doi: 10.1111/liv.12899. Epub 2015 Jul 16.
- Sugimoto K, Ito T, Yamamoto N, Shiraki K. Seven cases of autoimmune hepatitis that developed after drug-induced liver injury. Hepatology. 2011 Nov;54(5):1892-3. doi: 10.1002/hep.24513. Epub 2011 Aug 9. No abstract available.
- Fujiwara K, Yokosuka O. Histological discrimination between autoimmune hepatitis and drug-induced liver injury. Hepatology. 2012 Feb;55(2):657. doi: 10.1002/hep.24768. No abstract available.
- Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, Vierling JM; American Association for the Study of Liver Diseases. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010 Jun;51(6):2193-213. doi: 10.1002/hep.23584. No abstract available.
- Fontana RJ, Hayashi PH, Gu J, Reddy KR, Barnhart H, Watkins PB, Serrano J, Lee WM, Chalasani N, Stolz A, Davern T, Talwakar JA; DILIN Network. Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset. Gastroenterology. 2014 Jul;147(1):96-108.e4. doi: 10.1053/j.gastro.2014.03.045. Epub 2014 Mar 27.
- Wang JB, Huang A, Wang Y, Ji D, Liang QS, Zhao J, Zhou G, Liu S, Niu M, Sun Y, Tian H, Teng GJ, Chang BX, Bi JF, Peng XX, Xin S, Xie H, Ma X, Mao YM, Liangpunsakul S, Saxena R, Aithal GP, Xiao XH, Zhao J, Zou Z. Corticosteroid plus glycyrrhizin therapy for chronic drug- or herb-induced liver injury achieves biochemical and histological improvements: a randomised open-label trial. Aliment Pharmacol Ther. 2022 May;55(10):1297-1310. doi: 10.1111/apt.16902. Epub 2022 Mar 31.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2015
Primary Completion (Actual)
July 1, 2019
Study Completion (Actual)
July 1, 2019
Study Registration Dates
First Submitted
December 25, 2015
First Submitted That Met QC Criteria
January 7, 2016
First Posted (Estimate)
January 11, 2016
Study Record Updates
Last Update Posted (Actual)
August 11, 2020
Last Update Submitted That Met QC Criteria
August 7, 2020
Last Verified
July 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Chemically-Induced Disorders
- Digestive System Diseases
- Liver Diseases
- Drug-Related Side Effects and Adverse Reactions
- Poisoning
- Chemical and Drug Induced Liver Injury
- Chemical and Drug Induced Liver Injury, Chronic
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Neuroprotective Agents
- Protective Agents
- Prednisolone
- Methylprednisolone Acetate
- Methylprednisolone
- Methylprednisolone Hemisuccinate
- Prednisolone acetate
- Prednisolone hemisuccinate
- Prednisolone phosphate
Other Study ID Numbers
- BJ302-FGRXGB-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Drug-induced Liver Injury,Chronic
-
Beijing 302 HospitalCompletedDrug-induced Liver Injury,ChronicChina
-
Drug Induced Liver Disease Study GroupUnknownChronic Liver Disease | Acute Drug-induced Liver Injury
-
Institute of Liver and Biliary Sciences, IndiaUnknown
-
Xi'An Aolitai Pharmaceutical Technology Co LtdRecruitingDrug-Induced Liver Injury | Cholestatic Liver Injury | Mixed Liver InjuryChina
-
Korea Institute of Oriental MedicineDongGuk University; Korean Medicine Hospital of Pusan National University; Semyung... and other collaboratorsActive, not recruitingDrug Induced Liver Injury | Drug-Induced Kidney Injury | Herbal Medicine Adverse ReactionKorea, Republic of
-
Kennon HeardMcNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.CompletedDrug Induced Liver InjuryUnited States
-
Institute of Liver and Biliary Sciences, IndiaTerminatedDrug Induced Liver InjuryIndia
-
Beijing 302 HospitalUnknownDrug-Induced Liver InjuryChina
-
Beijing 302 HospitalUnknownDrug-Induced Liver InjuryChina
-
Beijing 302 HospitalUnknown
Clinical Trials on Methylprednisolone
-
Rennes University HospitalUnknownMultiple Sclerosis, Relapsing-RemittingFrance
-
Chang Gung Memorial HospitalRecruitingMucocutaneous Lymph Node SyndromeTaiwan
-
Fred LublinPfizer; National Multiple Sclerosis SocietyTerminatedMultiple SclerosisUnited States
-
Assistance Publique - Hôpitaux de ParisCompleted
-
Universidad Nacional Autonoma de MexicoInstituto Nacional de Neurología y NeurocirugíaEnrolling by invitationMethylprednisolone | Intranasal Administration | Patients With an Active Multiple Sclerosis RelapseMexico
-
LEO PharmaBayerCompleted
-
Assiut UniversityCompleted
-
University of Colorado, DenverUniversity of Pennsylvania; MallinckrodtTerminatedMultiple SclerosisUnited States
-
Fundação de Medicina Tropical Dr. Heitor Vieira...CompletedSARS-CoV Infection | Severe Acute Respiratory Syndrome (SARS) PneumoniaBrazil
-
Peking University People's HospitalBeijing HospitalUnknownImmune Thrombocytopenia