Ignite Creation Date:
2024-07-17 @ 10:48 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06470386
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-24
First Post:
2024-06-11
Brief Title:
The Efficacy and Safety of Alverine in the Treatment of Portal Hypertension in Patients With Liver Cirrhosis
Sponsor:
Shanghai Changzheng Hospital
Organization:
Shanghai Changzheng Hospital
Study Overview
Official Title:
The Efficacy and Safety of Compound Alverine Citrate Soft Capsules in the Treatment of Portal Hypertension in Patients With Liver Cirrhosis a Prospective Open-label Multicentre Randomised Controlled Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Study Overall Design
This trial is a prospective open-label multicenter randomized controlled clinical trial Subjects who meet the inclusion criteria and do not meet the exclusion criteria will be randomly assigned to either the Alverine treatment group or the Carvedilol treatment group in a 11 ratio after signing the informed consent form After randomization participants will enter a 24-week medication period Apart from the baseline period the efficacy of the treatment will be evaluated 24 weeks post-treatment The safety evaluation will be conducted according to the Common Terminology Criteria for Adverse Events CTCAE version 50 by the National Cancer Institute
Study Population
Patients with cirrhotic portal hypertension
Interventions
Alverine Group 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 mgday 1 capsule orally 3 times a day taken continuously for 24 weeks
Carvedilol Group Jinluo Carvedilol Tablets 625 mg manufactured by Qilu Pharmaceutical Co Ltd taken orally starting dose of 625 mg once a day gradually adjusted according to heart rate to 625 mg twice a day 125 mg in the morning and 625 mg in the evening 125 mg twice a day or adjusted to the maximum tolerated dose heart rate greater than 55 beatsmin and systolic blood pressure greater than 90 mmHg taken continuously for 24 weeks
Study Objectives
1 Primary Study Objective Evaluate the efficacy and safety of Compound Alverine Citrate Capsules in the treatment of cirrhotic portal hypertension
2 Secondary Study Objectives Evaluate the effect of Compound Alverine Citrate Capsules on the incidence of esophagogastric variceal bleeding and other cirrhotic decompensation events
3 Exploratory Study Objectives Evaluate the efficacy of Compound Alverine Citrate Capsules in the treatment of cirrhotic portal hypertension using other non-invasive detection methods Observe the effects of Compound Alverine Citrate Capsules on the multi-omics characteristics of cirrhosis reversal of portal hypertension recompensation of decompensated cirrhosis and prevention of the progression of cirrhosis to liver cancer
Study Endpoints
1 Primary Study Endpoints
1 The treatment response rate defined as a reduction in HVPG of 10 from baseline or a reduction to below 12 mmHg after 24 weeks of treatment
2 The incidence events and severity of adverse events serious adverse events and adverse events leading to treatment discontinuation after treatment evaluated according to CTCAE version 50
2 Secondary Study Endpoints
1 Incidence of esophagogastric variceal bleeding during treatment
2 Incidence of other cirrhotic decompensation events new onset or progression of ascites spontaneous bacterial peritonitis overt hepatic encephalopathy acute kidney injuryhepatorenal syndrome primary liver cancer etc during treatment
3 Reduction in HVPG from baseline after 24 weeks of treatment
4 Mortalityliver transplantation rate during treatment
5 Overall survival time of subjects
6 Reduction in mean arterial pressure MAP and heart rate from baseline after 24 weeks of treatment
3 Exploratory Study Endpoints
1 Changes in liver stiffness and spleen stiffness from baseline after 24 weeks of treatment
2 Improvement in liver function Child-Pugh score MELD score after 24 weeks of treatment
3 Changes in cardiac function left ventricular ejection fraction from baseline after 24 weeks of treatment
4 Changes in imaging characteristics bloodstool metabolomics characteristics portal hypertension reversal biomarkers cirrhosis recompensation biomarkers and cirrhosis progression to liver cancer biomarkers after 24 weeks of treatment
Sample Size Calculation
In animal experiments it was confirmed that there was no statistically significant difference in the effect of Alverine and Carvedilol in treating portal hypertension Literature reports indicate that the treatment response rate of Carvedilol for cirrhotic portal hypertension is approximately 60 Based on the sample size calculation method for non-inferiority trials with two samples with a non-inferiority margin δ020 a one-sided α0025 and β02 the calculated sample size for each group is 74 cases totaling 148 cases Considering a 20 dropout rate a total of 178 cases are needed
This trial is a prospective open-label multicenter randomized controlled clinical trial Subjects who meet the inclusion criteria and do not meet the exclusion criteria will be randomly assigned to either the Alverine treatment group or the Carvedilol treatment group in a 11 ratio after signing the informed consent form After randomization participants will enter a 24-week medication period Apart from the baseline period the efficacy of the treatment will be evaluated 24 weeks post-treatment The safety evaluation will be conducted according to the Common Terminology Criteria for Adverse Events CTCAE version 50 by the National Cancer Institute
Study Population
Patients with cirrhotic portal hypertension
Interventions
Alverine Group 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 mgday 1 capsule orally 3 times a day taken continuously for 24 weeks
Carvedilol Group Jinluo Carvedilol Tablets 625 mg manufactured by Qilu Pharmaceutical Co Ltd taken orally starting dose of 625 mg once a day gradually adjusted according to heart rate to 625 mg twice a day 125 mg in the morning and 625 mg in the evening 125 mg twice a day or adjusted to the maximum tolerated dose heart rate greater than 55 beatsmin and systolic blood pressure greater than 90 mmHg taken continuously for 24 weeks
Study Objectives
1 Primary Study Objective Evaluate the efficacy and safety of Compound Alverine Citrate Capsules in the treatment of cirrhotic portal hypertension
2 Secondary Study Objectives Evaluate the effect of Compound Alverine Citrate Capsules on the incidence of esophagogastric variceal bleeding and other cirrhotic decompensation events
3 Exploratory Study Objectives Evaluate the efficacy of Compound Alverine Citrate Capsules in the treatment of cirrhotic portal hypertension using other non-invasive detection methods Observe the effects of Compound Alverine Citrate Capsules on the multi-omics characteristics of cirrhosis reversal of portal hypertension recompensation of decompensated cirrhosis and prevention of the progression of cirrhosis to liver cancer
Study Endpoints
1 Primary Study Endpoints
1 The treatment response rate defined as a reduction in HVPG of 10 from baseline or a reduction to below 12 mmHg after 24 weeks of treatment
2 The incidence events and severity of adverse events serious adverse events and adverse events leading to treatment discontinuation after treatment evaluated according to CTCAE version 50
2 Secondary Study Endpoints
1 Incidence of esophagogastric variceal bleeding during treatment
2 Incidence of other cirrhotic decompensation events new onset or progression of ascites spontaneous bacterial peritonitis overt hepatic encephalopathy acute kidney injuryhepatorenal syndrome primary liver cancer etc during treatment
3 Reduction in HVPG from baseline after 24 weeks of treatment
4 Mortalityliver transplantation rate during treatment
5 Overall survival time of subjects
6 Reduction in mean arterial pressure MAP and heart rate from baseline after 24 weeks of treatment
3 Exploratory Study Endpoints
1 Changes in liver stiffness and spleen stiffness from baseline after 24 weeks of treatment
2 Improvement in liver function Child-Pugh score MELD score after 24 weeks of treatment
3 Changes in cardiac function left ventricular ejection fraction from baseline after 24 weeks of treatment
4 Changes in imaging characteristics bloodstool metabolomics characteristics portal hypertension reversal biomarkers cirrhosis recompensation biomarkers and cirrhosis progression to liver cancer biomarkers after 24 weeks of treatment
Sample Size Calculation
In animal experiments it was confirmed that there was no statistically significant difference in the effect of Alverine and Carvedilol in treating portal hypertension Literature reports indicate that the treatment response rate of Carvedilol for cirrhotic portal hypertension is approximately 60 Based on the sample size calculation method for non-inferiority trials with two samples with a non-inferiority margin δ020 a one-sided α0025 and β02 the calculated sample size for each group is 74 cases totaling 148 cases Considering a 20 dropout rate a total of 178 cases are needed
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None