The Multi Center, Randomized, Double-blind, Positive Controlled Study of Bicyclol in the Treatment of Acute DILI

The Multi Center, Randomized, Double-blind, Positive Controlled Phase II Clinical Trial of Bicyclol Tablets in the Treatment of Acute Drug-induced Liver Injury

The study adopted the superiority design of multi center, randomized, double-blind, positive control drug, dose finding, using two simulation skills. The qualified subjects, according to the ratio of 1:1:1, were randomized into low dose group, high dose group and positive drug control group, and received a treatment course of 4-8 weeks, all individuals were followed up for 4 weeks after drug withdrawal.

Study Overview

• Status: Completed
• Conditions: Drug-Induced Acute Liver Injury
• Intervention / Treatment: Drug: bicyclol tablet 25mg; Drug: bicyclol tablet 50mg; Drug: polyene phosphatidylcholine capsule 456mg

Detailed Description

Explore the safety and efficacy of different doses of bicyclol in treatment of acute drug-induced liver injury using polyene phosphatidylcholine capsule as the positive control drug.

The study adopted the design of multi center, randomized, double-blind, dose finding, positive control drug, superiority test, using two simulation skills. The qualified subjects, according to the ratio of 1:1:1, were randomized into low dose group and high dose group and positive drug control group, and received a treatment course of 4-8 weeks, all individuals were followed up for 4 weeks after drug withdrawal.

• Study Type: Interventional
• Enrollment (Actual): 244
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai Lung Hospital
  • Anhui
    • Hefei, Anhui, China
      • Anhui Provincial Hospital
  • Beijing
    • Beijing, Beijing, China, 101149
      • Beijing Chest hospital, Capital medical university
    • Beijing, Beijing, China
      • Beijing Ditan Hospital, Capital Medical University
  • Chongqing
    • Chongqing, Chongqing, China
      • The Second Affiliated Hospital of Chongqing Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Fuzhou General hospital of Nanjing Military Command
  • Henan
    • Weihui, Henan, China
      • The First Affiliated Hospital of Xinxiang Medical University
    • Zhengzhou, Henan, China
      • Henan Provincial People's Hospital
    • Zhengzhou, Henan, China
      • Henan Infectious Diseases Hospital
  • Hunan
    • Changsha, Hunan, China
      • The second Xiangya Hospital of Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • No.85 Hospital of PLA
    • Shanghai, Shanghai, China, 200127
      • Renji Hospital ，Shanghai Jiao Tong University School Of Medicine
    • Shanghai, Shanghai, China
      • Ruijin Hospital ，Shanghai Jiao Tong University School of Medicine
    • Shanghai, Shanghai, China
      • Shanghai Putuo District Central Hospital
    • Shanghai, Shanghai, China
      • Tongji Hospital of Tongji University
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Haihe Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. 18-75 years old, male or female;
2. Meet the standard of clinical diagnosis of acute drug-induced liver injury, the RUCAM causality scale score is more than or equal to 6 points. If the RUCAM causality scale score is 3-5,the subject needs three liver disease experts to confirm whether he is DILI patient, at least two of three liver disease experts should have the same judgment;
3. The serum ALT is between 3and 20 times ULN, but TBiL is less than or equal to 2 times ULN;
4. Liver biochemical indexes(ALT,AST,ALP,GGT,TBiL,albumin,prothrombin time) abnormalities lasted less than 90 days;
5. Patients can understand the nature of the experiment, the nature of the disease, the characteristic of drugs, related treatment methods and the risk they may need to bear if they participate in the test, and sign the informed consent.

Exclusion criteria:

1. Occurrent liver injury caused by other reasons, such as viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease etc;
2. Acute liver failure or liver function decompensation patient perform, such as hepatic encephalopathy, ascites, albumin is less than or equal to 35g / L, The international standardized ratio (INR) of thrombin is more than 1.5;
3. Serum creatinine is more than 1.5 times ULN;
4. Severe or life-threatening heart, lung, brain, kidney, gastrointestinal and systemic diseases;
5. Taking drugs that may affect observation of curative effect of the experimental drug during the study;
6. Allergy or intolerance to experimental drugs;
7. With no ability to express their complaints, such as mental illness and severe neurosis patient;
8. The patient can not cooperate and poor compliance;
9. Pregnant and lactating women or women preparing for pregnancy;
10. The patient participated in other clinical trials in 3 months before entering this study;
11. Using other liver-protective drugs except ursodeoxycholic acid or ademetionine within three days;
12. The researchers believe not suitable.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low dose group; Patients in the low dose group administrated bicyclol tablet 25mg orally, three times daily for 4-8 weeks.	Drug: bicyclol tablet 25mg; Patients in the low dose group administrated bicyclol tablet 25mg, one bicyclol blank analog tablet and two polyene phosphatidylcholine blank analog capsules orally, three times daily for 4-8 weeks.; Other Names: bicyclol blank analog tablet; polyene phosphatidylcholine blank analog capsule
Experimental: high dose group; Patients in the high dose group administrated bicyclol tablet 50mg orally, three times daily for 4-8 weeks.	Drug: bicyclol tablet 50mg; Patients in the high dose group administrated bicyclol tablet 50mg and two polyene phosphatidylcholine blank analog capsules orally, three times daily for 4-8 weeks.; Other Names: polyene phosphatidylcholine blank analog capsule
Active Comparator: positive drug control group; Patients in the positive drug control group administrated polyene phosphatidylcholine capsule 456mg orally, three times daily for 4-8 weeks.	Drug: polyene phosphatidylcholine capsule 456mg; Patients in the positive drug control group administrated polyene phosphatidylcholine capsules 456mg and two bicyclol blank analog tablets orally, three times daily for 4-8 weeks.; Other Names: bicyclol blank analog tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The decline range of serum ALT after 4 weeks of treatment	The decrease value of serum ALT after 4 weeks of treatment compared to the baseline	after 4 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The decrease value of serum AST compared to the baseline of treatment for 1, 2, 4, 6, 8 weeks and follow-up for 2, 4 weeks	The decrease value of serum AST compared to the baseline	after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks
The decrease value of serum ALT compared to the baseline of treatment for 1, 2, 6, 8 weeks and follow-up for 2, 4 weeks	The decrease value of serum ALT compared to the baseline	after 1, 2, 6, 8 weeks treatment and follow-up for 2, 4 weeks
The decrease rate of serum ALT compared to the baseline of treatment for 1, 2, 4, 6, 8 weeks and follow-up for 2, 4 weeks	The decrease rate of serum ALT compared to the baseline	after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks
The time from treatment to ALT normalization	The time from treatment to ALT normalization	treatment period
The ratio of subjects whose ALT and AST declined more than 50% compared to the base line of treatment for 1, 2, 4, 6, 8 weeks and follow-up for 2, 4 weeks	The ratio of subjects whose ALT and AST declined more than 50% compared to the base line	after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks
The serum ALT and AST normalization rate of treatment for 1, 2, 4, 6, 8 weeks and follow-up for 2, 4 weeks	The serum ALT and AST normalization rate	after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks
The area under curve of ALT and AST of treatment for 1, 2, 4, 6, 8 weeks and follow-up for 2, 4 weeks	The area under curve of ALT and AST	after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks

Collaborators and Investigators

• Sponsor: Drug Induced Liver Disease Study Group
• Collaborators: Beijing Union Pharmaceutical Factory

Publications and helpful links

General Publications

• Tang J, Gu J, Chu N, Chen Y, Wang Y, Xue D, Xie Q, Li L, Mei Z, Wang X, Li J, Chen J, Li Y, Yang C, Wang Y, Shang J, Xie W, Hu P, Li D, Zhao L, Lan P, Wang C, Chen C, Mao Y. Efficacy and safety of bicyclol for treating patients with idiosyncratic acute drug-induced liver injury: A multicenter, randomized, phase II trial. Liver Int. 2022 Aug;42(8):1803-1813. doi: 10.1111/liv.15290. Epub 2022 May 25.

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2017
• Primary Completion (Actual): June 10, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: October 24, 2016
• First Submitted That Met QC Criteria: October 25, 2016
• First Posted (Estimate): October 26, 2016

Study Record Updates

• Last Update Posted (Actual): April 28, 2020
• Last Update Submitted That Met QC Criteria: April 26, 2020
• Last Verified: April 1, 2020

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; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Polyene phosphatidylcholine
• Other Study ID Numbers: YL-SHC-2015

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No