The Safety and Efficacy of Alverine in the Treatment of Cirrhotic Portal Hypertension
NCT Number: NCT06473493
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2|PHASE3
Conditions: Hypertension, Portal
Interventions: DRUG: Alverine
Sponsor: Shanghai Changzheng Hospital
Collaborators: Shanghai East Hospital|Daping Hospital, Army Medical Center of PLA
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 30
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-06
Completion Date: 2025-03

Summary:
Study Overall Design: This trial is a prospective, multi-center, single-arm, exploratory clinical study. Subjects who meet the inclusion criteria and do not meet the exclusion criteria will receive Compound Alverine Citrate Capsules (Lejiansu; specification: each capsule contains 60 mg of Alverine Citrate and 300 mg of Simethicone; produced by Laboratoires Mayoly Spindler, France) after signing the informed consent form. The dosage is 180 mg/day (1 capsule orally three times a day) for a treatment period of 24 weeks. Apart from the baseline period, efficacy will be evaluated at the end of the 24-week treatment period. Safety assessments will be conducted throughout the trial. The safety evaluation will be performed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 by the National Cancer Institute.

Study Population: Patients with cirrhotic portal hypertension

Intervention: Compound Alverine Citrate Capsules (Lejiansu; each capsule contains 60 mg of Alverine Citrate and 300 mg of Simethicone; manufactured by the French company UCB Pharma), 180 mg/day (1 capsule orally, 3 times a day), taken continuously for 24 weeks.

Study Objectives: To evaluate the safety and efficacy of Compound Alverine Citrate Capsules in treating portal hypertension in patients with cirrhosis.

Study Endpoints Primary Endpoints

1. Safety Assessment: Incidence of adverse events, serious adverse events, and adverse events leading to discontinuation of treatment (evaluated according to CTCAE version 5.0).
2. Efficacy Assessment: The response rate at 24 weeks of treatment, defined as a reduction in HVPG by ≥ 10% from baseline or a reduction to below 12 mmHg.

Secondary Endpoints

1. HVPG Changes: The absolute value and percentage change in HVPG from baseline after 24 weeks of treatment.
2. Decompensation Events: Incidence of cirrhosis decompensation events during treatment, including esophageal/gastric variceal bleeding and re-bleeding, new or worsening ascites, spontaneous bacterial peritonitis, overt hepatic encephalopathy, and acute kidney injury/hepatorenal syndrome.
3. 12-Week Response Rate: The treatment response rate at 12 weeks.
4. Mortality and Transplantation: Rates of death, liver transplantation, and liver disease-related mortality during the treatment period.

Exploratory Endpoints

1. Cardiac Function: Changes in cardiac function from baseline after 24 weeks of treatment.
2. Liver and Spleen Stiffness: Changes in liver and spleen stiffness from baseline after 24 weeks of treatment.
3. Esophageal Varices: Status of esophageal varices after 24 weeks of treatment.

Sample Size Calculation: This trial is a single-arm, exploratory clinical study, and plans to enroll 30 subjects.

Primary Outcome Measures: Safety assessment: the incidence of adverse events, serious adverse events, and adverse events leading to treatment discontinuation after treatment., The incidence of adverse events, serious adverse events, and adverse events leading to treatment discontinuation after treatment., 24 weeks|24-week response rate, The response rate to treatment, defined as the percentage of patients with a decrease in HVPG of ≥10% from baseline or a decrease to below 12 mmHg after 24 weeks of treatment., 24 weeks
Secondary Outcome Measures: HVPG changes: the absolute value change in HVPG from baseline after 24 weeks of treatment, The absolute value change in HVPG from baseline after 24 weeks of treatment, 24 weeks|HVPG changes: the percentage change in HVPG from baseline after 24 weeks of treatment, The percentage change in HVPG from baseline after 24 weeks of treatment, 24 weeks|The incidence of decompensation events, Incidence of cirrhosis decompensation events during treatment, including esophageal/gastric variceal bleeding and re-bleeding, new or worsening ascites, spontaneous bacterial peritonitis, overt hepatic encephalopathy, and acute kidney injury/hepatorenal syndrome., 24 weeks|12-week response rate, The treatment response rate at 12 weeks, 12 weeks|Mortality rate, Rates of death and liver disease-related mortality during the treatment period, 24 weeks|Transplantation rate, Rates of liver transplantation during the treatment period, 24 weeks
Other Outcome Measures: Cardiac function changes, Changes in cardiac function (LVEF) from baseline after 24 weeks of treatment, 24 weeks|Liver stiffness changes, Changes in liver stiffness from baseline after 24 weeks of treatment, 24 weeks|Spleen stiffness changes, Changes in spleen stiffness from baseline after 24 weeks of treatment, 24 weeks|Esophageal varices changes, Size of esophageal varices after 24 weeks of treatment, 24 weeks