Back to resultsThe Multi Center, Randomized, Double-blind, Positive Controlled Study of Bicyclol in the Treatment of Acute DILI
Primary Purpose
Drug-Induced Acute Liver Injury
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
bicyclol tablet 25mg
bicyclol tablet 50mg
polyene phosphatidylcholine capsule 456mg
Sponsored by
About this trial
This is an interventional treatment trial for Drug-Induced Acute Liver Injury
Eligibility Criteria
Inclusion criteria:
- 18-75 years old, male or female;
- 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;
- The serum ALT is between 3and 20 times ULN, but TBiL is less than or equal to 2 times ULN;
- Liver biochemical indexes(ALT,AST,ALP,GGT,TBiL,albumin,prothrombin time) abnormalities lasted less than 90 days;
- 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:
- Occurrent liver injury caused by other reasons, such as viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease etc;
- 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;
- Serum creatinine is more than 1.5 times ULN;
- Severe or life-threatening heart, lung, brain, kidney, gastrointestinal and systemic diseases;
- Taking drugs that may affect observation of curative effect of the experimental drug during the study;
- Allergy or intolerance to experimental drugs;
- With no ability to express their complaints, such as mental illness and severe neurosis patient;
- The patient can not cooperate and poor compliance;
- Pregnant and lactating women or women preparing for pregnancy;
- The patient participated in other clinical trials in 3 months before entering this study;
- Using other liver-protective drugs except ursodeoxycholic acid or ademetionine within three days;
- The researchers believe not suitable.
Sites / Locations
- Anhui Provincial Hospital
- Beijing Chest Hospital, Capital Medical University
- Beijing Ditan Hospital, Capital Medical University
- The second affiliated Hospital of Chongqing Medical University
- Fuzhou General Hospital of Nanjing Military Command
- The First affiliated Hospital of Xinxiang Medical University
- Henan Infectious Diseases Hospital
- Henan Provincial People's Hospital
- The Second Xiangya Hospital of Central South University
- Jiangsu Province Hospital
- Renji Hospital ，Shanghai Jiao Tong University School of Medicine
- No.85 hospital of PLA
- Ruijin Hospital ，Shanghai Jiao Tong University School of Medicine
- Shanghai Putuo District Central Hospital
- Tongji Hospital of Tongji University
- Tianjin Haihe Hospital
- Shanghai Lung Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
low dose group
high dose group
positive drug control group
Arm Description
Patients in the low dose group administrated bicyclol tablet 25mg orally, three times daily for 4-8 weeks.
Patients in the high dose group administrated bicyclol tablet 50mg orally, three times daily for 4-8 weeks.
Patients in the positive drug control group administrated polyene phosphatidylcholine capsule 456mg orally, three times daily for 4-8 weeks.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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
The time from treatment to ALT normalization
The time from treatment to ALT normalization
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
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
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
Full Information
NCT ID
NCT02944552
First Posted
October 24, 2016
Last Updated
April 26, 2020
Sponsor
Drug Induced Liver Disease Study Group
Collaborators
Beijing Union Pharmaceutical Factory
1. Study Identification
Unique Protocol Identification Number
NCT02944552
Brief Title
The Multi Center, Randomized, Double-blind, Positive Controlled Study of Bicyclol in the Treatment of Acute DILI
Official Title
The Multi Center, Randomized, Double-blind, Positive Controlled Phase II Clinical Trial of Bicyclol Tablets in the Treatment of Acute Drug-induced Liver Injury
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
August 18, 2017 (Actual)
Primary Completion Date
June 10, 2019 (Actual)
Study Completion Date
July 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Drug Induced Liver Disease Study Group
Collaborators
Beijing Union Pharmaceutical Factory
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Drug-Induced Acute Liver Injury
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
244 (Actual)
8. Arms, Groups, and Interventions
Arm Title
low dose group
Arm Type
Experimental
Arm Description
Patients in the low dose group administrated bicyclol tablet 25mg orally, three times daily for 4-8 weeks.
Arm Title
high dose group
Arm Type
Experimental
Arm Description
Patients in the high dose group administrated bicyclol tablet 50mg orally, three times daily for 4-8 weeks.
Arm Title
positive drug control group
Arm Type
Active Comparator
Arm Description
Patients in the positive drug control group administrated polyene phosphatidylcholine capsule 456mg orally, three times daily for 4-8 weeks.
Intervention Type
Drug
Intervention Name(s)
bicyclol tablet 25mg
Other Intervention Name(s)
bicyclol blank analog tablet, polyene phosphatidylcholine blank analog capsule
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
bicyclol tablet 50mg
Other Intervention Name(s)
polyene phosphatidylcholine blank analog capsule
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
polyene phosphatidylcholine capsule 456mg
Other Intervention Name(s)
bicyclol blank analog tablet
Intervention Description
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.
Primary Outcome Measure Information:
Title
The decline range of serum ALT after 4 weeks of treatment
Description
The decrease value of serum ALT after 4 weeks of treatment compared to the baseline
Time Frame
after 4 weeks of treatment
Secondary Outcome Measure Information:
Title
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
Description
The decrease value of serum AST compared to the baseline
Time Frame
after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks
Title
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
Description
The decrease value of serum ALT compared to the baseline
Time Frame
after 1, 2, 6, 8 weeks treatment and follow-up for 2, 4 weeks
Title
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
Description
The decrease rate of serum ALT compared to the baseline
Time Frame
after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks
Title
The time from treatment to ALT normalization
Description
The time from treatment to ALT normalization
Time Frame
treatment period
Title
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
Description
The ratio of subjects whose ALT and AST declined more than 50% compared to the base line
Time Frame
after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks
Title
The serum ALT and AST normalization rate of treatment for 1, 2, 4, 6, 8 weeks and follow-up for 2, 4 weeks
Description
The serum ALT and AST normalization rate
Time Frame
after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks
Title
The area under curve of ALT and AST of treatment for 1, 2, 4, 6, 8 weeks and follow-up for 2, 4 weeks
Description
The area under curve of ALT and AST
Time Frame
after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
18-75 years old, male or female;
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;
The serum ALT is between 3and 20 times ULN, but TBiL is less than or equal to 2 times ULN;
Liver biochemical indexes(ALT,AST,ALP,GGT,TBiL,albumin,prothrombin time) abnormalities lasted less than 90 days;
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:
Occurrent liver injury caused by other reasons, such as viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease etc;
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;
Serum creatinine is more than 1.5 times ULN;
Severe or life-threatening heart, lung, brain, kidney, gastrointestinal and systemic diseases;
Taking drugs that may affect observation of curative effect of the experimental drug during the study;
Allergy or intolerance to experimental drugs;
With no ability to express their complaints, such as mental illness and severe neurosis patient;
The patient can not cooperate and poor compliance;
Pregnant and lactating women or women preparing for pregnancy;
The patient participated in other clinical trials in 3 months before entering this study;
Using other liver-protective drugs except ursodeoxycholic acid or ademetionine within three days;
The researchers believe not suitable.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yimin Mao
Organizational Affiliation
RenJi Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Chengwei Chen
Organizational Affiliation
No.85 hospital of PLA
Official's Role
Study Chair
Facility Information:
Facility Name
Anhui Provincial Hospital
City
Hefei
State/Province
Anhui
Country
China
Facility Name
Beijing Chest Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
101149
Country
China
Facility Name
Beijing Ditan Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
Country
China
Facility Name
The second affiliated Hospital of Chongqing Medical University
City
Chongqing
State/Province
Chongqing
Country
China
Facility Name
Fuzhou General Hospital of Nanjing Military Command
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350025
Country
China
Facility Name
The First affiliated Hospital of Xinxiang Medical University
City
Weihui
State/Province
Henan
Country
China
Facility Name
Henan Infectious Diseases Hospital
City
Zhengzhou
State/Province
Henan
Country
China
Facility Name
Henan Provincial People's Hospital
City
Zhengzhou
State/Province
Henan
Country
China
Facility Name
The Second Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
Country
China
Facility Name
Jiangsu Province Hospital
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
Renji Hospital ，Shanghai Jiao Tong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200127
Country
China
Facility Name
No.85 hospital of PLA
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Ruijin Hospital ，Shanghai Jiao Tong University School of Medicine
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Shanghai Putuo District Central Hospital
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Tongji Hospital of Tongji University
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Tianjin Haihe Hospital
City
Tianjin
State/Province
Tianjin
Country
China
Facility Name
Shanghai Lung Hospital
City
Shanghai
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
35567757
Citation
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.
Results Reference
derived
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The Multi Center, Randomized, Double-blind, Positive Controlled Study of Bicyclol in the Treatment of Acute DILI
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