Clinical Evaluation of Simcyp-Guided Simvastatin Dosing in Patients With Liver Cirrhosis

March 9, 2026 updated by: Naira Galal, Kafrelsheikh University

Dose Prediction for Statins and Anticoagulant Medications in Cirrhotic Patients Using Simcyp Program: Applications in Clinical Practice

This prospective open-label parallel pilot clinical study evaluated the efficacy and safety of physiologically based pharmacokinetic (PBPK)-guided simvastatin dosing in Child-Pugh A and B cirrhotic patients with portal hypertension over a 3-month period. Twenty-two patients were enrolled following screening, and portal hemodynamic, laboratory, and safety parameters were assessed.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This was a prospective, open-label, parallel interventional clinical study conducted over a three-month period in Egyptian cirrhotic patients with portal hypertension.

Thirty patients were screened for eligibility. Eight patients were excluded as they did not meet the predefined inclusion criteria. A total of 22 patients were enrolled and completed the study.

Adult patients aged ≥18 years with confirmed liver cirrhosis and portal hypertension without a history of variceal bleeding were eligible for inclusion. Patients with severe renal impairment, pregnancy, known hypersensitivity to statins, active malignancy within the previous two years, or recent use of strong CYP3A4 inhibitors were excluded.

Patients were stratified according to Child-Pugh (CP) classification into CP class A and CP class B groups. Simvastatin doses were determined using physiologically based pharmacokinetic (PBPK) modeling via the Simcyp® Simulator to account for hepatic impairment-related changes in drug exposure.

CP class A patients received simvastatin 15 mg once daily, while CP class B patients received simvastatin 5 mg once daily.

Clinical evaluation included Doppler ultrasonographic assessment of portal and hepatic hemodynamics, including portal vein diameter, portal vein velocity, congestion index, and hepatic artery resistive index. Laboratory investigations included liver function tests (ALT, AST, total bilirubin, and serum albumin), renal function tests (serum creatinine and BUN), complete blood count, and creatine kinase for safety monitoring.

Patients were followed monthly throughout the 3-month study period, with systematic documentation of adverse events.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Cairo, Egypt
        • Kafrelsheikh University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult patients aged ≥ 18 years
  • Confirmed diagnosis of liver cirrhosis (clinical, laboratory, or imaging evidence)
  • Evidence of portal hypertension (clinical findings and/or Doppler ultrasound measurements)
  • No previous history of variceal bleeding
  • Child-Pugh class A or B

Exclusion Criteria:

  • Active hepatocellular carcinoma
  • Severe renal impairment (eGFR < 30 mL/min/1.73 m²)
  • Baseline creatine kinase (CK) > 3 × upper limit of normal
  • Known hypersensitivity to simvastatin
  • Current therapy with strong CYP3A4 inhibitors
  • Any active malignancy in the last 2 years
  • Pregnancy or lactation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1_Child-Pugh A
10 patients with Child-Pugh A received Simvastatin 15 mg once daily.
Drug: Simvastatin 15 mg
Simvastatin is an HMG-CoA reductase inhibitor that improves endothelial nitric oxide bioavailability and reduces intrahepatic vascular resistance, thereby potentially lowering portal pressure.
Experimental: Group 2_Child-Pugh B
12 patients with Child-Pugh B received Simvastatin 5 mg once daily.
Drug: Simvastatin 5 mg
Simvastatin is an HMG-CoA reductase inhibitor that improves endothelial nitric oxide bioavailability and reduces intrahepatic vascular resistance, thereby potentially lowering portal pressure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Portal Vein Diameter (mm)
Time Frame: 3 months
Portal vein diameter will be measured as a Doppler ultrasound parameter to evaluate changes related to portal hypertension
3 months
Change in Portal Vein Velocity (cm/s)
Time Frame: 3 months
Portal vein velocity will be assessed as an indicator reflecting changes in portal hypertension
3 months
Change in Hepatic Artery Resistance Index (HARI)
Time Frame: 3 months
The Hepatic Artery Resistance Index will be measured as a Doppler-based marker associated with changes in portal hypertension
3 months
Change in Congestion Index (CI) (cm/ [cm/s2])
Time Frame: 3 months
The congestion index will be evaluated as a Doppler-derived surrogate marker for portal hypertension severity
3 months
Change in Modified Vascular Liver Index (MVLI) (cm/s)
Time Frame: 3 months
MVLI will be measured as part of the Doppler assessment reflecting changes in portal hypertension
3 months
Change in Platelet Count (×10⁹/L)
Time Frame: 3 months
Platelet count will be assessed as a hematologic surrogate marker associated with portal hypertension.
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse effects related to Simvastatin
Time Frame: 3 months
Adverse effects will be monitored throughout the study period, including clinical evaluation and laboratory investigations such as liver function tests (ALT, AST), creatine kinase (CK), and documentation of any muscle-related or gastrointestinal symptoms.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kafrelsheikh University

Investigators

  • Principal Investigator: Naira Galal, BSc in Pharmacy, Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
  • Study Director: Noha Mahmoud El-khodary, PhD, Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2024

Primary Completion (Actual)

March 15, 2025

Study Completion (Actual)

June 15, 2025

Study Registration Dates

First Submitted

March 4, 2026

First Submitted That Met QC Criteria

March 4, 2026

First Posted (Actual)

March 10, 2026

Study Record Updates

Last Update Posted (Actual)

March 11, 2026

Last Update Submitted That Met QC Criteria

March 9, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KFSIRB200-127 (Registry Identifier: Kafrelsheikh University IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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