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

Drug-Induced Acute Liver Injury Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02944552
• Other study ID #: YL-SHC-2015
• Status: Completed
• Phase: Phase 2
• Start date: August 18, 2017
• Est. completion date: July 31, 2019

Study information

• Verified date: April 2020
• Source: Drug Induced Liver Disease Study Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 244
• Est. completion date: July 31, 2019
• Est. primary completion date: June 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chemical and Drug Induced Liver Injury
• Drug-Induced Acute Liver Injury

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
China	Beijing Chest Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Ditan Hospital, Capital Medical University	Beijing	Beijing
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	The second affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Fuzhou General Hospital of Nanjing Military Command	Fuzhou	Fujian
China	Anhui Provincial Hospital	Hefei	Anhui
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	No.85 hospital of PLA	Shanghai	Shanghai
China	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 Lung Hospital	Shanghai
China	Shanghai Putuo District Central Hospital	Shanghai	Shanghai
China	Tongji Hospital of Tongji University	Shanghai	Shanghai
China	Tianjin Haihe Hospital	Tianjin	Tianjin
China	The First affiliated Hospital of Xinxiang Medical University	Weihui	Henan
China	Henan Infectious Diseases Hospital	Zhengzhou	Henan
China	Henan Provincial People's Hospital	Zhengzhou	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Drug Induced Liver Disease Study Group	Beijing Union Pharmaceutical Factory

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	The time from treatment to ALT normalization	The time from treatment to ALT normalization	treatment period
Secondary	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
Secondary	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
Secondary	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