NCT07459972

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

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

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: Kafrelsheikh University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• Liver Cirrhosis
• Portal Hypertension Related to Cirrhosis

Interventions

Type	Name	Description
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.
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.

Timeline

• Start date: 2024-03-15
• Primary completion: 2025-03-15
• Completion: 2025-06-15
• First posted: 2026-03-10
• Last updated: 2026-03-11

Locations

1 site across 1 country: Egypt