Carvedilol and Alverine in Portal Hypertension

NCT06696248 | Not Yet Recruiting Phase 2

• 1 other identifier: CZXH-PH-ALV-2403
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

Brief summaries of CZXH-PH-ALV-2403 The goal of this clinical trial is to learn if the combination of alverine and carvedilol works to treat portal hypertension in adult patients with liver cirrhosis. It will also learn about the safety of alverine. The main question it aims to answer is: For patients with liver cirrhosis and portal hypertension who have been treated with carvedilol at a dose of up to 15 mg/day or at a lower dose that is the maximum tolerated for at least 3 months, and still have a hepatic venous pressure gradient (HVPG) of 12 mmHg or higher and up to and including 20 mmHg, can the addition of alverine help to reduce portal hypertension? On the basis of maintaining unchanged routine hepatoprotective and symptomatic supportive treatments and the original dose of carvedilol, participants will be administered with compound alverine citrate capsules (Le Jian Su; specification: each capsule contains alverine citrate 60 mg and simeticone 300 mg; manufactured by Laboratoires MAYOLY SPINDLER), at a dosage of 180 mg/day (1 capsule orally, 3 times a day), for a continuous period of 24 weeks.

Conditions

Hypertension, Portal

Keywords

Cirrhotic portal hypertension; Alverine; Pharmacological therapy

Outcome Measures

Primary Outcomes (1)

• The 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 Outcomes (7)

• Degree of decrease in HVPG compared to baseline HVPG after 24 weeks of treatment.

  24 weeks

• Incidence of cirrhosis decompensation events during treatment.

  24 weeks

• The 12-week response rate

  12 weeks

• Degree of decrease in HVPG compared to baseline HVPG after 12 weeks of treatment.

  12 weeks

• Degree of decrease in mean arterial pressure (MAP) compared to baseline MAP after 24 weeks of treatment.

  24 weeks

Study Arms (1)

Carvedilol + Alverine Group

EXPERIMENTAL

On the basis of maintaining unchanged routine hepatoprotective and symptomatic supportive treatments and the original dose of carvedilol, participants will be administered with compound alverine citrate capsules (Le Jian Su; specification: each capsule contains alverine citrate 60 mg and simeticone 300 mg; manufactured by Laboratoires MAYOLY SPINDLER), at a dosage of 180 mg/day (1 capsule orally, 3 times a day), for a continuous period of 24 weeks.

Drug: Carvedilol and alverine

Interventions

Carvedilol and alverine DRUG

On the basis of maintaining unchanged routine hepatoprotective and symptomatic supportive treatments and the original dose of carvedilol, participants will be administered with compound alverine citrate capsules (Le Jian Su; specification: each capsule contains alverine citrate 60 mg and simeticone 300 mg; manufactured by Laboratoires MAYOLY SPINDLER), at a dosage of 180 mg/day (1 capsule orally, 3 times a day), for a continuous period of 24 weeks.

Carvedilol + Alverine Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18 to 80 years old (inclusive), no gender restrictions;
• Patients with liver cirrhosis diagnosed by clinical, laboratory, imaging examinations, and/or liver biopsy;
• Treated with carvedilol at a dose of up to 15 mg/day or at a lower dose that is the maximum tolerated for at least 3 months, with HVPG≥12 mmHg and ≤20 mmHg;
• Agree to participate and sign the informed consent form.

You may not qualify if:

• Those who have taken alverine, papaverine, or their derivatives (such as papaverine hydrochloride preparations, trimebutine maleate, etc.) within 4 weeks before enrollment;
• Those who have undergone transjugular intrahepatic portosystemic shunt (TIPS) or other interventional treatments affecting portal pressure (including splenic embolization, splenic microwave treatment, etc.) or liver transplantation;
• Those who have had overt hepatic encephalopathy, esophageal and gastric variceal bleeding within 2 weeks before enrollment; those who have undergone endoscopic treatment for esophageal and gastric varices within 1 week before enrollment or are planned for endoscopic treatment;
• Those who have used somatostatin and its analogs, vasopressin, terlipressin, dopamine, norepinephrine, and other vasoactive drugs within 1 week before enrollment;
• Those with a history of heavy alcohol consumption within 12 weeks before enrollment and cannot abstain from alcohol during the study period (equivalent ethanol intake of ≥30 g/day for males and ≥20 g/day for females);
• Serum total bilirubin levels ≥3×ULN (for patients with autoimmune liver disease, serum total bilirubin levels ≥5×ULN), or serum sodium levels \<125 mmol/L, or white blood cell count \<1×10\^9/L, or platelet count \<30×10\^9/L, or International Normalized Ratio (INR) \>1.8; or serum creatinine ≥1.2×ULN;
• Presence of thrombosis in the portal venous system (including portal vein, splenic vein, superior mesenteric vein, etc.) and cavernous transformation of the portal vein; those with a history of portal venous system thrombosis who have no definite thrombosis detected in the portal venous system within 2 weeks before enrollment may be included;
• HBV DNA or HCV RNA \> the lower limit of detection; patients with active hepatitis C receiving antiviral treatment; those who have received anti-HBV treatment for less than 24 weeks;
• Those with uncontrollable current infections (pulmonary infections, abdominal infections, HIV, etc.) within 4 weeks before enrollment;
• Those with poorly controlled hypertension, diabetes, or other severe heart, lung diseases;
• Those diagnosed or suspected to have malignant tumors, including liver cancer;
• Known allergies to alverine, papaverine, or their derivatives (such as papaverine hydrochloride preparations, trimebutine maleate, etc.), or simethicone, or carvedilol; patients with contraindications to carvedilol: New York Heart Association Class IV decompensated heart failure requiring intravenous inotropic agents; asthma, chronic obstructive pulmonary disease (COPD) with bronchospasm; second- or third-degree atrioventricular block, severe bradycardia (heart rate less than 50 beats per minute), sick sinus syndrome (including sinoatrial block); cardiogenic shock; severe hypotension (systolic blood pressure less than 85 mmHg);
• Those with glaucoma;
• Those with mental abnormalities;
• Pregnant or breastfeeding women, or women who do not rule out the possibility of pregnancy;

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead
• Shanghai East Hospital: collaborator
• Army Medical Center of PLA: collaborator

MeSH Terms

Conditions

Hypertension, Portal

Interventions

Carvedilol; alverine

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Study Officials

• Wei-Fen Xie, M.D.

  Shanghai Changzheng Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chang-Peng Zhu, M.D.

CONTACT

86-13671547663; zhuchangpeng@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Department of Gastroenterology, Changzheng Hospital

Study Record Dates

• First Submitted: November 12, 2024
• First Posted: November 20, 2024
• Study Start: November 15, 2024
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: November 20, 2024

Record last verified: 2024-11