Atorvastatin Use and Portal Hypertension in Patients With Hepatitis B Virus-related Liver Cirrhosis: A Randomized Controlled Trial

Phase 2

Not yet recruiting

• Conditions: Portal Hypertension; Hepatitis B
• Interventions: Drug: Atorvastatin 10mg; Drug: Placebo

• Registration Number: NCT05483894
• Lead Sponsor: Samsung Medical Center

Brief Summary

To evaluate whether atorvastatin can improve portal hypertension in patients with chronic hepatitis B related compensated cirrhosis with portal hypertension

Detailed Description

In order to derive a reliable correlation between statin use and the reduction of portal hypertension, it is necessary to proceed with a clinical study with a high level of evidence, such as a randomized controlled clinical trial study. In addition, previous small randomized controlled trials had a limitation in that patients with various causes of liver cirrhosis were included. In this study, only patients diagnosed with chronic hepatitis B and compensated cirrhosis who are taking antiviral treatment will be included in the study, and in patients whose viral activity are suppressed by taking antiviral treatment, it was investigated whether statin administration had a significant effect in additionally improving portal pressure. We want to prove it through a randomized controlled clinical trial study.

Study Timeline

• Status Verified: 2022-07
• Study First Submitted: 2022-07-25
• Study First Submitted QC: 2022-07-29
• Last Update Submitted: 2022-07-29
• Study Start: 2022-08-01
• Study First Posted: 2022-08-02
• Last Update Posted: 2022-08-02
• Primary Completion: 2024-07-31
• Study Completion: 2025-01-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1. Adults between 19 and 69 years of age

2. If HBsAg positivity has been observed for more than 6 months or a clinical history of chronic hepatitis B is confirmed

3. When liver cirrhosis is diagnosed histologically, radiologically, or clinically (if one or more of A-D is applicable) A. When stage F4 fibrosis is confirmed by liver biopsy B. When splenomegaly is observed with morphological changes (surface nodularity and hypertrophy of the caudate lobe) appropriate for liver cirrhosis.

   C. If the platelet count is less than 100,000/mm3 in two consecutive tests D. When esophageal varices or gastric varices are confirmed by upper gastrointestinal endoscopy

4. If the serum HBV DNA is well controlled to 2000 International Unit (IU)/mL or less while taking antiviral treatment

5. When the splenic elasticity measured by two-dimensional shear wave elastography is greater than 25 kilopascal(kPa)

6. When informed consent is possible

Exclusion Criteria

1. Hepatitis C or HIV co-infected person
2. Those who continuously drink more than the standard (alcohol intake exceeding 20g per day)
3. In case of decreased liver function with Child Pugh score of 7 or higher
4. History of decompensated cirrhosis: history of ascites, spontaneous bacterial peritonitis, hepatic coma, varicose bleeding, hepatic nephrotic syndrome
5. If there is a history of cancer (except for cases where there is no recurrence for 5 years after treatment due to early solid organ tumors (early gastric cancer, thyroid cancer))
6. If there is a serious comorbidity whose life expectancy is estimated to be less than 3 years
7. In case of chronic kidney disease estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2
8. If portal vein thrombosis is diagnosed
9. Previous intrahepatic portal vein shunt intervention or liver transplantation
10. A history of statin administration within the last 2 years
11. In case of side effects from previous statin administration (drug-related hepatotoxicity, muscle toxicity, allergic reaction, etc.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental group	Atorvastatin 10mg	Atorvastatin 10mg once daily for 24 weeks
Control group	Atorvastatin 10mg	Placebo once daily for 12 weeks and then Atorvastatin 10mg once daily for 12 weeks
Control group	Placebo	Placebo once daily for 12 weeks and then Atorvastatin 10mg once daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Response rate of 12 weeks of atorvastatin in experimental group and 12 weeks of placebo in control group	12 weeks	A responder is defined as a case in which the percentage change in spleen stiffness decreased by 10% or more from baseline after 12 weeks of atorvastatin or placebo administration. When the ratio of the number of responders to the number of participants in each group is defined as the response rate, there is a difference in the response rates between the experimental group and the control group.

Secondary Outcome Measures

Name	Time	Method
Response rate of 12 weeks of placebo in control group and 12 weeks of atorvastatin in control group	12 weeks	The response rate after 12 weeks of placebo administration in the control group is different from the response rate after 12 weeks of atorvastatin administration (24 weeks after the start of the study) in the control group at 12 weeks.
Adverse events	24 weeks	Frequency of adverse events (hepatotoxicity, muscle toxicity) after atorvastatin administration
Response rate of 12 weeks of placebo in control group and 24 weeks of atorvastatin in experimental group	24 weeks	The response rate after 12 weeks of placebo administration in the control group is different from the response rate after 24 weeks of atorvastatin administration in the experimental group.
Response rate of 12 weeks of atorvastatin in experimental group and 24 weeks of atorvastatin in experimental group	24 weeks	After 12 weeks of atorvastatin administration, the response rate of the experimental group in which the percentage change in spleen stiffness decreased by 10% or more compared to the baseline value after 12 weeks of administration is different from the response rate after 24 weeks of the experimental group, in which the percentage change in spleen stiffness decreased by more than 10% compared to the baseline after 24 weeks of administration.