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

Study Overview
=================
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.

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

Conditions
-----------------
Drug-Induced Acute Liver Injury

Intervention / Treatment
-----------------
* Drug: bicyclol tablet 25mg
* Drug: bicyclol tablet 50mg
* Drug: polyene phosphatidylcholine capsule 456mg


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low dose group<br>Patients in the low dose group administrated bicyclol tablet 25mg orally, three times daily for 4-8 weeks. | Drug: bicyclol tablet 25mg<br>* 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.<br>* Other names: polyene phosphatidylcholine blank analog capsule;|
| Experimental: high dose group<br>Patients in the high dose group administrated bicyclol tablet 50mg orally, three times daily for 4-8 weeks. | Drug: bicyclol tablet 50mg<br>* 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.<br>* Other names: polyene phosphatidylcholine blank analog capsule;|
| Active Comparator: positive drug control group<br>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<br>* 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.<br>* 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 |