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Drug-induced Liver Injury,ChronicPhase 1/2NCT03266146

36 Weeks Short-Term Optimization Treatment of Glucocorticosteroid in the Patients With Chronic Recurrent DILI

A Phase 1/2 study testing 36 Weeks Methylprednisolone and 48 weeks Methylprednisolone in people with Drug-induced Liver Injury,Chronic, run by Beijing 302 Hospital at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is to observe the efficacy and safety of 36 weeks short-term optimization treatment of glucocorticosteroid in the patients with chronic recurrent drug-induced liver injury (DILI). Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Drug-induced Liver Injury,Chronic
What is being tested?
36 Weeks Methylprednisolone and 48 weeks Methylprednisolone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
1 siteChina
Study dates
2 Sep 2017to 31 Jan 2023
Phase
Phase 1/2
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 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Meet with ACG clinic guidelines for diagnostic criteria of chronic DILI;
  • The time of recurrence is 1 or more than 1;
  • The definition of recurrence, meet any of the following conditions:
  • the level of serum AST or ALT is elevated more than 5 fold ULN;
  • the level of serum AST or ALT is two times higher than before;
  • Meet any of the following conditions:
Show all 12Show fewer
  • 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.
  • -

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Beijing 302 hospital

    Beijing, 100039

Other trials in China

About this study

Official title: The Efficacy and Safety of 36 Weeks Short-Term Optimization Treatment of Glucocorticosteroid in the Patients With Chronic Recurrent Drug-Induced Liver Injury

This study is to observe the efficacy and safety of 36 weeks short-term optimization treatment of glucocorticosteroid in the patients with chronic recurrent drug-induced liver injury (DILI).

Read the 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 1100 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. About 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. In our pre-clinical trials (NCT02651350), we found that the rate of recurrence of the glucocorticoid treatment group was significant lower (<10%) than the control group (about 50%) (P <0.001) and there was significant difference of liver histological change during baseline and treatment end between the glucocorticoid treatment group and the control group. Meanwhile, we did not find obvious glucocorticoid's side effect in the glucocorticoid treatment group. At the same time, we found that there was good effect in 36 weeks glucocorticoid treatment in several patients. Therefore, we shall design two groups on the basis of the ratio of 1:1, namely, 36 weeks of glucocorticoid treatment group and 48 weeks of glucocorticoid treatment group in order to evaluate the efficacy and safety of 36 weeks short-term optimization treatment of glucocorticosteroid in the patients with chronic recurrent DILI.

Participants in 36 weeks of 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 20 weeks and reduction in doses of methylprednisolone by 4 mg per 4 weeks until drug withdrawal. Participants in 36 weeks of glucocorticoid treatment group also will receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA).Participants will then be followed for 24 weeks. Participants in 48 weeks of 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 48 weeks of treatment group also will receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA).Participants will then be followed for 24 weeks.

The efficacy and safety of 36 weeks short-term optimization treatment of glucocorticosteroid in the patients with chronic recurrent DILI will be observed and compared with 48 weeks glucocorticosteroid treatment during the treatment and follow-up period.

Being tested
36 Weeks Methylprednisolone, 48 weeks Methylprednisolone
Keywords
Drug-induced Liver Injury, Recurrence, Methylprednisolone, Short-term
Medical subject headings
Chemical and Drug Induced Liver Injury, Chronic, Chemical and Drug Induced Liver Injury, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 36 Weeks MethylprednisoloneDrug

    Also called MEDROL,NDC0009-0056-02

    Participants in 36 weeks of 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 20 weeks and reduction in doses of methylprednisolone by 4 mg per 4 weeks until drug withdrawal. Participants in 36 weeks of glucocorticoid treatment group also will receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA).The total treatment duration will be 36 weeks. Follow-up duration is 24 weeks.

  • 48 weeks MethylprednisoloneDrug

    Also called MEDROL,NDC0009-0056-02

    Participants in 48 weeks of 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 36 weeks of glucocorticoid treatment group also will receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA).The total treatment duration will be 48 weeks. Follow-up duration is 24 weeks.

Study groups in NCT03266146
Study groupRoleWhat they receive
36 Weeks MethylprednisoloneExperimentalParticipants in 36 weeks of 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 20 weeks and reduction in doses of methylprednisolone by 4 mg per 4 weeks until drug withdrawal. Participants in 36 weeks of glucocorticoid treatment group also will receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA). Participants will then be followed for 24 weeks.
Receives: Drug: 36 Weeks Methylprednisolone
48 Weeks MethylprednisoloneExperimentalParticipants in 48 weeks of 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 48 weeks of treatment group also will receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA). Participants will then be followed for 24 weeks.
Receives: Drug: 48 weeks Methylprednisolone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recurrence rate of illness, namely, appearance of obviously abnormal liver function again during treatment and follow-up period. The definition of recurrence: The level of AST or ALT is elevated more than 5 fold ULN or is two times higher than before.

    To analyze the clinical efficacy of glucocorticosteroid treatment

    Measured: From week 1 to week 60 or 72

Secondary outcomes (2)

  1. The liver histological changes between two liver biopsies (baseline and treatment end)

    To analyze the clinical efficacy of glucocorticosteroid treatment

    Measured: At week 0 and at week 36 week or 48 week

  2. Days of normalization or falling by half compared to admission of liver functions including serum levels of ALT, AST, TBIL,GGT and ALP.

    To analyze the clinical efficacy of glucocorticosteroid treatment

    Measured: From week 1 to week 36 or 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Aug 2017
  2. Study start2 Sep 2017
  3. Primary completion31 Jan 2023
  4. Study completion31 Jan 2023

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03266146
Sponsor's protocol ID
BJ302-FGRXGB-003
Status last verified
Feb 2023
First submitted
26 Aug 2017
Last updated
15 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 24935270

  • 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.

    PubMed 26671593

  • 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.

    PubMed 24507072

  • 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.

    PubMed 21338638

  • 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.

    PubMed 21674554

  • 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.

    PubMed 21396413

  • 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.

    PubMed 26104271

  • 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.

    PubMed 21725992

  • 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.

    PubMed 22038865

  • 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.

    PubMed 20513004

  • 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.

    PubMed 24681128

  • Stine JG, Chalasani NP. Drug Hepatotoxicity: Environmental Factors. Clin Liver Dis. 2017 Feb;21(1):103-113. doi: 10.1016/j.cld.2016.08.008. Epub 2016 Oct 13.

    PubMed 27842766

  • Hayashi PH, Rockey DC, Fontana RJ, Tillmann HL, Kaplowitz N, Barnhart HX, Gu J, Chalasani NP, Reddy KR, Sherker AH, Hoofnagle JH; Drug-Induced Liver Injury Network (DILIN) Investigators. Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatology. 2017 Oct;66(4):1275-1285. doi: 10.1002/hep.29283. Epub 2017 Aug 26.

    PubMed 28543844

  • Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, Watkins PB, Navarro V, Barnhart H, Gu J, Serrano J; United States Drug Induced Liver Injury Network. Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology. 2015 Jun;148(7):1340-52.e7. doi: 10.1053/j.gastro.2015.03.006. Epub 2015 Mar 6.

    PubMed 25754159

  • Huang A, Zhu Y, Liu S, Sun Y, Liu Z, Liang QS, Zhao J, Chang BX, Bi JF, Liu JT, Zhai XR, Xie H, Li N, Tian H, Han L, Zhuang Y, Ma H, Teng GJ, Zhang W, Aithal GP, Ji D, Zhao J, Zou Z. An optimized short-term steroid therapy for chronic drug-induced liver injury: A prospective randomized clinical trial. Liver Int. 2024 Jun;44(6):1435-1447. doi: 10.1111/liv.15899. Epub 2024 Mar 14.

    PubMed 38483145

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing 36 Weeks Methylprednisolone and 48 weeks Methylprednisolone in people with Drug-induced Liver Injury,Chronic, run by Beijing 302 Hospital at 1 site in China.

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 12 inclusion and 7 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 15 Feb 2023. 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 China. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

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?

Recurrence rate of illness, namely, appearance of obviously abnormal liver function again during treatment and follow-up period. The definition of recurrence: The level of AST or ALT is elevated more than 5 fold ULN or is two times higher than before. (time frame: From week 1 to week 60 or 72). 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 NCT03266146, which also lists 15 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 15 Feb 2023.

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