Efficacy of Simvastatin in Alcoholic Liver Fibrosis (SIMFIB)

Efficacy of Simvastatin in Reducing Liver Fibrosis in Patients With Advanced Fibrosis Due to Alcohol: Randomized, Double-blind, Placebo-controlled Clinical Trial

Evaluate the efficacy of simvastatin in reducing liver fibrosis in patients with advanced fibrosis due to alcohol

Study Overview

• Status: Recruiting
• Conditions: Liver Fibrosis; Alcohol Abuse
• Intervention / Treatment: Drug: Simvastatin 40mg

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Gratacos; Phone Number: 34 932275400; Email: acruceta@recerca.clinic.cat
• Study Contact Backup: Name: ana cruceta; Phone Number: 34-932275400; Email: acruceta@recerca.clinic.cat

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Jordi Gratacos
    • Contact: ana cruceta; Phone Number: 93 2275400; Email: acruceta@recerca.clinic.cat
    • Contact: ana cruceta; Phone Number: 392275400; Email: acruceta@recerca.clinic.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Chronic alcohol-related liver disease according to international guidelines (EASL, European Association for the Study of the Liver) and with data of significant liver fibrosis obtained in the diagnostic biopsy at the beginning of the study or in the last biopsy of the patient within 6 months prior to randomization. Significant liver fibrosis is defined by a score on the Ishak fibrosis scale of between 3 and 6.
3. Patients in the compensated chronic liver disease phase defined by the absence of clinical decompensations at the time of entering the study, with or without data of portal hypertension.
4. Women of childbearing potential must have a negative urine pregnancy test prior to study enrollment and agree to use highly effective contraceptive methods (combined oral pill, injectable or implanted contraceptive, intrauterine device / hormone delivery system intrauterine) during the study.

Exclusion Criteria:

1. Patients receiving statins or fibrates.
2. Patients with other etiologies of liver disease in addition to alcohol: hepatitis C, hepatitis B, autoimmune hepatitis, Wilson's disease, or hemochromatosis.
3. Patients in whom hepatitis C has been cured with antivirals in the 2 years prior to inclusion in the study.
4. Patients with a CK elevation of 50% or more above the upper limit of normal at the time of study inclusion.
5. Gastrointestinal bleeding due to portal hypertension within 12 months prior to inclusion in the study.
6. Clinical hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy, in the 12 months prior to inclusion in the study.
7. Patients in need of diuretic treatment in the previous 12 months to control ascites or hydrothorax.
8. Spontaneous bacterial peritonitis within 12 months prior to study enrollment.
9. Hepatocellular carcinoma of any stage.
10. Patients with known muscle disease.
11. Patients with previous rhabdomyolysis.
12. Patients being treated with strong CYP3A4 enzyme inhibitors (see section 5.2: Concomitant drugs, not allowed and allowed).
13. Patients being treated with drugs with possible interactions with simvastatin (see section 5.2: Concomitant drugs, not allowed and allowed).
14. Patients with a history of significant extrahepatic disease with poor short-term prognosis, including New York Heart Association Grade III / V congestive heart failure, GOLD COPD> 2, chronic kidney disease with serum creatinine> 2mg / dL or under therapy of kidney replacement.
15. Patients with extrahepatic malignancies, including solid tumors and hematologic malignancies.
16. Patients with a history or increased risk of intestinal obstruction.
17. Pregnancy or breastfeeding.
18. Patients included in other clinical trials during the previous month.
19. Patients with mental disabilities, language barriers, poor social support or any other reason considered by the researcher as essential for adequate understanding, cooperation or compliance with the study.
20. Presence of data on alcoholic hepatitis in liver biopsy upon inclusion.
21. Patients with contraindications for statins.
22. Known hypersensitivity to simvastatin.
23. Refusal to sign the informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control arm	Drug: Simvastatin 40mg; participants will receive a capsule containing 4 tablets simvastatin 10 mg (40 mg total) every 24 hours at night
Experimental: Treatment arm	Drug: Simvastatin 40mg; participants will receive a capsule containing 4 tablets simvastatin 10 mg (40 mg total) every 24 hours at night

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline biopsy in histological fibrosis Ishak score (0-4 range. higher scores mean a worse result)	Change from range baseline biopsy in histological fibrosis score measured through the Ishak scale at 18 months.	18 months

Collaborators and Investigators

• Sponsor: Anna Cruceta
• Investigators: Study Chair: Pere Gines, Md, Hospital Clinic of Barcelona

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2022
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 12, 2021
• First Submitted That Met QC Criteria: July 20, 2021
• First Posted (Actual): July 21, 2021

Study Record Updates

• Last Update Posted (Actual): December 4, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Digestive System Diseases; Liver Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism; Fibrosis; Liver Cirrhosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: SIMFIB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No