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

A Multi-center, Randomized, Double-blind, Positive-controlled Phase Ⅲ Clinical Trial of Bicyclol Tablets in the Treatment of Acute Drug-induced Liver Injury

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

Study Overview

• Status: Recruiting
• Conditions: Drug-Induced Acute Liver Injury
• Intervention / Treatment: Drug: bicyclol, 25mg/ tablet; Drug: polyene phosphatidylcholine capsules, 228mg/ particle.

Detailed Description

Further evaluated the safety and efficacy of bicyclol in the 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, positive control drug, superiority test, using the double-blind double-simulating skills. The qualified subjects, according to the ratio of 1:1, were randomized into experimental group and positive drug control group and received a treatment course of 4 weeks, all individuals were followed up for 4 weeks after drug withdrawal.

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yimin Mao; Phone Number: 13003175438; Email: maoym11968@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Recruiting
      • Renji Hospital ，Shanghai Jiao Tong University School Of Medicine
      • Contact: Yimin Mao; Phone Number: 13003175438; Email: maoym11968@163.com
    • Shanghai, Shanghai, China
      • Not yet recruiting
      • 905th Hospital of PLA Navy
      • Contact: Chengwei Chen; Phone Number: 13901989118; Email: ccw2@163.com

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. When screening, the threshold of serum liver biochemical test meets one of the following criteria: i: ALT≥5ULN; ii: ALP≥2ULN; iii: ALT≥3ULN, and TBiL≥2ULN;
3. During the screening, the patients with hepatocellular injury type or mixed type DILI mainly manifested by a significant increase in ALT were mainly selected;
4. Meeting 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, meanwhile, at least two of three liver disease experts should have the same judgment.
5. Liver biochemical indexes (ALT, AST, ALP, GGT, TBiL, albumin, prothrombin time) abnormalities lasted no more than 90 days;
6. 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. Liver injury is caused by other reasons, such as viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, etc.;
2. Patients with acute or subacute liver failure; patients with acute liver failure or liver decompensation, such as hepatic encephalopathy, ascites, albumin is less than normal value, International normalized ratio (INR) of prothrombin time greater than 1.5;
3. Cholestatic DILI;
4. Serum creatinine is more than 1.5 times ULN;
5. Severe or life-threatening heart, lung, brain, kidney, gastrointestinal and systemic diseases;
6. Simultaneous application of drugs that affect the efficacy of this trial;
7. Allergy or intolerance to experimental drugs;
8. With no ability to express their complaints, such as mental illness and severe neurosis patient;
9. The patient can not cooperate and poor compliance;
10. Pregnant and lactating women or women preparing for pregnancy;
11. The patient participated in other clinical trials in 3 months before entering this study;
12. Using other liver-protective drugs except ursodeoxycholic acid or ademetionine within last 3 days;
13. The researchers consider 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Experimental group: each oral bicyclol 50mg, three times daily for 4 weeks.	Drug: bicyclol, 25mg/ tablet; Experimental group: each oral bicyclol 50mg, three times daily for 4 weeks.
Active Comparator: Control group; Control group: each oral polyene phosphatidylcholine 456mg, three times daily for 4 weeks.	Drug: polyene phosphatidylcholine capsules, 228mg/ particle.; Control group: each oral polyene phosphatidylcholine 456mg, three times daily for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The normalization rate of serum ALT after 4 weeks of treatment	The normalization rate of serum ALT after 4 weeks of treatment	After 4 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The normalization rate of serum ALT after 2 weeks of treatment	The normalization rate of serum ALT after 2 weeks of treatment	After 2 weeks of treatment
The decrease value in serum ALT relative to baseline at 2 weeks of treatment;	The decrease value in serum ALT relative to baseline at 2 weeks of treatment;	After 2 weeks of treatment
The decrease value in serum ALT relative to baseline at 4 weeks of treatment;	The decrease value in serum ALT relative to baseline at 4 weeks of treatment;	After 4 weeks of treatment
The time from the start of treatment to the return of ALT	The time from the start of treatment to the return of ALT	Up to 4 weeks
The normalization rate of serum AST after 2 weeks of treatment	The normalization rate of serum AST after 2 weeks of treatment	After 2 weeks of treatment
The normalization rate of serum AST after 4 weeks of treatment	The normalization rate of serum AST after 4 weeks of treatment	After 4 weeks of treatment
The decrease in serum AST relative to baseline at 2 weeks of treatment.	The decrease in serum AST relative to baseline at 2 weeks of treatment.	After 2 weeks of treatment
The decrease in serum AST relative to baseline at 4 weeks of treatment.	The decrease in serum AST relative to baseline at 4 weeks of treatment.	After 4 weeks of treatment

Collaborators and Investigators

• Sponsor: Drug Induced Liver Disease Study Group
• Collaborators: Beijing Union Pharmaceutical Factory
• Investigators: Study Chair: Chengwei Chen, 905th Hospital of PLA Navy

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2021
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: September 9, 2021
• First Submitted That Met QC Criteria: September 21, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 3, 2022
• Last Verified: August 1, 2022

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: SHC-2020

Drug and device information, study documents

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