Clinical trial NCT02944552: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Drug-Induced Acute Liver Injury
Lead sponsor: Drug Induced Liver Disease Study Group
Sponsor class: OTHER
Collaborators: name: Beijing Union Pharmaceutical Factory Ltd
First posted: 2016-10-26
Enrollment: 244
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The decline range of serum ALT after 4 weeks of treatment
timeFrame: after 4 weeks of treatment
Secondary outcomes:
measure: 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
timeFrame: after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks
measure: 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
timeFrame: after 1, 2, 6, 8 weeks treatment and follow-up for 2, 4 weeks
measure: 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
timeFrame: after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks
measure: The time from treatment to ALT normalization
timeFrame: treatment period
measure: 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
timeFrame: after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks
measure: The serum ALT and AST normalization rate of treatment for 1, 2, 4, 6, 8 weeks and follow-up for 2, 4 weeks
timeFrame: after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks
measure: The area under curve of ALT and AST of treatment for 1, 2, 4, 6, 8 weeks and follow-up for 2, 4 weeks
timeFrame: after 1, 2, 4, 6, 8 weeks treatment and follow-up for 2, 4 weeks
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Chest Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Ditan Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: The second affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Fuzhou General Hospital of Nanjing Military Command
state: Fujian
city: Weihui
country: China
facility: The First affiliated Hospital of Xinxiang Medical University
state: Henan
city: Zhengzhou
country: China
facility: Henan Infectious Diseases Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Renji Hospital ，Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: No.85 hospital of PLA
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital ，Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Putuo District Central Hospital
state: Shanghai
city: Shanghai
country: China
facility: Tongji Hospital of Tongji University
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Haihe Hospital
state: Tianjin
city: Shanghai
country: China
facility: Shanghai Lung Hospital
Study officials:
affiliation: RenJi Hospital
name: Yimin Mao
role: STUDY_CHAIR
affiliation: No.85 hospital of PLA
name: Chengwei Chen
role: STUDY_CHAIR
References:
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.