NCT07397481

Clinical Application of Simcyp-Guided Doses of Antihypertensive Drugs in Cirrhotic Patients

Dose Prediction for Antihypertensive Medications in Cirrhotic Patients Using Simcyp Program: Applications in Clinical Practice

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Kafrelsheikh University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This was a prospective, open-label, randomized, parallel pilot clinical study conducted over 3 months on 50 Egyptian cirrhotic patients with arterial hypertension and portal hypertension, evaluating the real-world applicability of selected PBPK-guided dosing regimens. Patients were stratified according to Child-Pugh class (CP-A or CP-B) and randomly assigned to receive either nebivolol or carvedilol at doses corresponding to the closest commercially available strengths to Simcyp®-predicted doses. Clinical evaluation included serial blood pressure measurements, comprising systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR). Doppler ultrasonographical assessment was performed to evaluate portal and hepatic hemodynamics, including portal vein diameter, portal vein velocity, congestion index, hepatic artery resistive index, and modified vascular liver index. Routine laboratory investigations were conducted to assess efficacy and safety and included liver function tests (serum albumin, total bilirubin, alanine aminotransferase \[ALT\], and aspartate aminotransferase \[AST\]), kidney function tests (serum creatinine and blood urea nitrogen \[BUN\]), and fasting blood glucose. Patients were followed on a monthly basis, with systematic documentation of adverse events throughout the study period.

Detailed description

This was a prospective, randomized, parallel, open-label pilot clinical study conducted over three months on Egyptian cirrhotic patients with arterial hypertension and portal hypertension. Adult patients aged \>18 years with confirmed liver cirrhosis, concomitant arterial hypertension, and portal hypertension without a history of variceal bleeding were eligible for inclusion. Patients with renal disorders or on dialysis, pregnancy, known hypersensitivity to the study medications, active malignancy within the previous two years, or recent use of drugs interacting with antihypertensive agents were excluded. Patients were stratified according to Child-Pugh (CP) classification into CP class A and CP class B and randomly allocated into four treatment groups to receive either nebivolol or carvedilol at doses corresponding to the closest commercially available strengths to Simcyp®-predicted doses. CP class A patients were assigned to Group A (nebivolol 5 mg once daily) or Group B (carvedilol 12.5 mg once daily), while CP class B patients were assigned to Group C (nebivolol 2.5 mg once daily) or Group D (carvedilol 6.25 mg once daily). Clinical evaluation included serial blood pressure measurements, comprising systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR), which were assessed at baseline and after 2, 4, 8, and 12 weeks of treatment. Doppler ultrasonographical assessment was performed to evaluate portal and hepatic hemodynamics, including portal vein diameter, portal vein velocity, congestion index, hepatic artery resistive index, and modified vascular liver index. Routine laboratory investigations were conducted to assess efficacy and safety and included liver function tests (serum albumin, total bilirubin, alanine aminotransferase \[ALT\], and aspartate aminotransferase \[AST\]), kidney function tests (serum creatinine and blood urea nitrogen \[BUN\]), CBC and fasting blood glucose. Patients were followed monthly throughout the study period, with systematic documentation of adverse events. During the study, four patients from CP class A discontinued participation and were excluded from the final analysis.

Conditions

• Liver Cirrhosis
• Arterial Hypertension

Interventions

Type	Name	Description
DRUG	Nebivolol 5 mg	Nebivolol is a third-generation cardio-selective β-1 adrenergic blocker with nitric oxide-mediated vasodilatory properties and it is primarily used to treat hypertension . Nebivolol reduces intrahepatic vascular resistance by enhancing nitric oxide (NO) production within the hepatic endothelium, thereby lowering portal pressure.
DRUG	Carvedilol 12.5 mg	Carvedilol is used to treat hypertension and it lowers blood pressure effectively through a combination of β adrenergic blockade and α-1-mediated vasodilation. Carvedilol lowers portal pressure by β1-mediated reduction of cardiac output, β2-mediated splanchnic vasoconstriction, and additional α1-adrenergic blockade, which induces intrahepatic vasodilation, thereby reducing portal hypertension.
DRUG	Nebivolol 2.5 mg	Nebivolol is a third-generation cardio-selective β-1 adrenergic blocker with nitric oxide-mediated vasodilatory properties and it is primarily used to treat hypertension . Nebivolol reduces intrahepatic vascular resistance by enhancing nitric oxide (NO) production within the hepatic endothelium, thereby lowering portal pressure.
DRUG	Carvedilol 6.25 mg	Carvedilol is used to treat hypertension and it lowers blood pressure effectively through a combination of β adrenergic blockade and α-1-mediated vasodilation. Carvedilol lowers portal pressure by β1-mediated reduction of cardiac output, β2-mediated splanchnic vasoconstriction, and additional α1-adrenergic blockade, which induces intrahepatic vasodilation, thereby reducing portal hypertension.

Timeline

• Start date: 2024-03-01
• Primary completion: 2025-03-01
• Completion: 2025-06-01
• First posted: 2026-02-09
• Last updated: 2026-02-09

Locations

1 site across 1 country: Egypt