Efficacy and Safety of Polyene Phosphatidylcholine in Treatment of Patients With Acute Drug-induced Liver Injury

A Multicenter, Randomized, Single-blind, Active-controlled Trial of The Efficacy and Safety of Polyene Phosphatidylcholine in Patients With Acute Drug-induced Liver Injury

The purpose of this study is to explore the efficacy and the safety of polyene phosphatidylcholine Injection in patients with acute drug-induced liver injury after 2-4 weeks of treatment.

Study Overview

• Status: Completed
• Conditions: Acute Drug Induced Liver Injury
• Intervention / Treatment: Drug: Polyene phosphatidylcholine injection 930 mg QD; Drug: Magnesium Isoglycyrrhizinate injection 200 mg QD

Detailed Description

This study is a phase IV study in subjects with acute drug-induced liver injury. As designed, the study will include a screening period of up to 1 week, 2 to 4 weeks of treatment, and 1 week of safety follow-up. The eligible subjects will randomly be assigned to polyene phosphatidylcholine group or magnesium isoglycyrrhizinate group to receive single-blind treatment with a ratio of 1:1.

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • The Second Hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China
      • Beijing Chest Hospital of Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China
      • Mengchao Hepatobiliary Hospital of Fujian Medical University
  • Guangdong
    • Shenzhen, Guangdong, China
      • ShenZhen People's Hospital
  • Henan
    • Zhengzhou, Henan, China
      • The Sixth People's Hospital of Zhengzhou
  • Jiangsu
    • Zhenjiang, Jiangsu, China
      • The Third Hospital of Zhenjiang Affiliated Jiangsu University
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Pulmonary Hospital
    • Shanghai, Shanghai, China
      • RenJi Hospital
    • Shanghai, Shanghai, China
      • Tongji Hospital

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:

• Age ≥ 18 and ≤ 75 years, Male or female patients
• Alanine aminotransferase (ALT) ≥ 3 x upper limit of normal (ULN) and Total bilirubin (TBIL) ≤ 5 x upper limit of normal (ULN)
• The Roussel Uclaf Causality Assessment Method (RUCAM) score is more than or equal to 6 points. The patients with RUCAM score of 3-5 needs to be determined by all three investigators that the liver injury is likely to be caused by drugs
• The duration of the current liver injury does not exceed 6 months

Exclusion Criteria:

• Liver injury caused by other diseases, such as viral hepatitis, alcoholic and non-alcoholic fatty liver disease, or autoimmune liver disease
• Acute liver failure or liver function decompensation, such as hepatic encephalopathy, ascites, albumin is less than 35g / L, the international standardized ratio (INR) of thrombin is more than 1.5
• Anemia or thrombocytopenia, hemoglobin is below 80 g/L, platelet count below 50,000 platelets per microliter
• Serum creatinine is more than 1.5 times ULN
• Severe hypokalemia, severe hypernatremia
• Patients have severe uncontrolled hypertension
• Severe diseases of vital organs such as heart, lung, brain, kidney, and gastrointestinal tract
• Treatment with polyene phosphatidylcholine injection or magnesium isoglycyrrhizinate injection within 5 days before informed consent
• Allergy or intolerance to benzyl alcohol and study drugs
• With no ability to express their complaints, such as mental illness and severe neurosis patient
• Pregnant or breastfeeding women, fertile women or men are reluctant to use contraception to avoid pregnancy during the trial
• Participation in another trial within 3 months before informed consent
• Patients who are considered by the investigator as inappropriate for the trial for other reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Polyene Phosphatidylcholine	Drug: Polyene phosphatidylcholine injection 930 mg QD; Polyene phosphatidylcholine injection 930mg, diluted with 5% glucose solution 250ml, once a day, at least 2 weeks but no more than 4 weeks.
Active Comparator: Magnesium Isoglycyrrhizinate	Drug: Magnesium Isoglycyrrhizinate injection 200 mg QD; Magnesium isoglycyrrhizinate injection 200mg, diluted with 5% glucose solution 250ml, once a day, at least 2 weeks but no more than 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum ALT normalization rate	The serum ALT normalization rate of treatment for 2-4 weeks	After 2-4 weeks treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
The serum ALT normalization rate for 1, 2 and 3 weeks	After 1, 2 and 3 weeks treatment
Changes in serum ALT compared to the baseline for 1, 2, 3 and 4 weeks	After 1, 2, 3 and 4 weeks treatment
The ratio of subjects whose ALT declined more than 50% compared to the base line for 1, 2, 3 and 4 weeks	After 1, 2, 3 and 4 weeks treatment
The serum AST normalization rate for 1, 2, 3 and 4 weeks	After 1, 2, 3 and 4 weeks treatment
Changes in serum AST compared to the baseline for 1, 2, 3 and 4 weeks	After 1, 2, 3 and 4 weeks treatment
The serum TBIL normalization rate for 1, 2, 3 and 4 weeks	After 1, 2, 3 and 4 weeks treatment
Changes in serum TBIL compared to the baseline for 1, 2, 3 and 4 weeks	After 1, 2, 3 and 4 weeks treatment
Changes in serum ALP and GGT compared to the baseline for 1, 2, 3 and 4 weeks	After 1, 2, 3 and 4 weeks treatment
The Incidence of Treatment-Emergent Adverse Events over time	After 2 to 4 weeks of treatment and 1 week of safety follow-up

Collaborators and Investigators

• Sponsor: Sichuan Haisco Pharmaceutical Group Co., Ltd
• Investigators: Study Chair: Yimin Mao, M.D., RenJi Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2020
• Primary Completion (Actual): October 21, 2020
• Study Completion (Actual): November 2, 2020

Study Registration Dates

• First Submitted: October 14, 2020
• First Submitted That Met QC Criteria: October 14, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): November 24, 2020
• Last Update Submitted That Met QC Criteria: November 22, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: ADILI
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Liver Diseases; Drug-Related Side Effects and Adverse Reactions; Poisoning; Wounds and Injuries; Chemical and Drug Induced Liver Injury; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Polyene phosphatidylcholine
• Other Study ID Numbers: HSK-28-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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