Spironolactone on Fibrosis Progrssion-Portal Hypertension(FP-PH)in Cirrhosis

Study Overview
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Brief Summary
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The aim of this study is to investigate the effects of spironolactone on liver fibrosis progression and portal pressure gradient in patients with advanced chronic liver disease. Eligible cirrhosis patients were 2:1 randomized to either combination (carvedilol and spironolactone) or single (carvedilol) therapy group. Changes in virtual portal pressure gradient (vPPG) of portal trunk (calculated based on reconstructed 3D model and measured blood flow velocity), liver stiffness measurement (Fibroscan) and serum markers of liver fibrogenesis were documented at baseline and six months later.

Official Title
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Effects of Spironolactone on Fibrosis Progression and Portal Pressure in Patients With Advanced Chronic Liver Disease

Conditions
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Cirrhosis, Portal Hypertension

Intervention / Treatment
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* Drug: Spironolactone and carvedilol
* Drug: Carvedilol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Proven cirrhosis based on histology or unequivocal clinical, sonographic and laboratory findings Exclusion Criteria: Treatment with β-blockers or diuretics in the last 3 months Severe cardiopulmonary or renal insufficiency Chronic alcohol abuse Can't tolerate side effects of oral carvedilol or spironolactone History of variceal bleeding Malignancy Portal vein thrombosis History of partial splenic embolization or splenectomy Moderate or tense ascites

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Carvedilol<br>Carvedilol starts at 6.25mg/d and increases to 12.5mg/d in next week as a maintainence dose | Drug: Spironolactone and carvedilol<br>* Patients are treated with carvedilol in combination with spironolactone.<br>* Other names: Combination therapy;|
| Experimental: Spironolactone and carvedilol<br>Carvedilol starts at 6.25mg/d and increases to 12.5mg/d in next week as a maintainence dose Spironolactone is added after carvedilol being tolerated, which starts with 20mg/d and increases to 40mg/d as a maintainence dose | Drug: Carvedilol<br>* Patients are treated with carvedilol only.<br>* Other names: Single therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virtual portal pressure gradient(vPPG) | Calculated based on reconstructed 3D portal trunk using anatomical information extracted from CT angiography and blood flow velocity measured by Doppler ultrasound | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver stiffness measurement (LSM) | Detected using FibroScan | 6 months | 
| Occurence of portal hypertension-related complications | variceal bleeding, ascites, hepatic encephalopathy | 6 months |