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

February 4, 2026 updated by: Mai Tarek, Kafrelsheikh University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

40

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
    • Egypt
      • Cairo, Egypt, 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:

  • Age of patients > 18 years.
  • Diagnosed with cirrhosis
  • Have cardiovascular disease(Hypertension )
  • Presence of portal hypertension
  • No history of variceal bleeding

Exclusion Criteria:

  • Patients with kidney disorder or dialysis
  • Hypersensitivity to study medications
  • Active cancer history in the last 2 years
  • Taking drugs that interact with antihypertensive drugs in the last two weeks
  • Pregnancy

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: • Group A (n = 10): Child-Pugh class A patients received nebivolol at a dose of 5 mg once daily.
Nebivolol at a dose of 5 mg (Nevilob 5 mg®, Marcyrl Pharmaceutical Industries, Egypt)
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.
Other Names:
  • Nevilob 5mg
Active Comparator: • Group B (n = 10): Child-Pugh class A patients received carvedilol at a dose of 12.5 mg once daily.
Carvedilol at a dose of 12.5 mg (Carvipress 12.5 mg®, Global Napi Pharmaceuticals, Egypt)
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.
Other Names:
  • Carvipress 12.5 mg
Active Comparator: Group C (n = 10): Child-Pugh B patients received nebivolol 2.5 mg once daily
Nebivolol at a dose of 2.5 mg (Nevilob 2.5 mg®, Marcyrl Pharmaceutical Industries, Egypt)
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.
Other Names:
  • Nevilob 2.5mg
Active Comparator: Group D (n = 10): Child-Pugh B patients received carvedilol 6.25 mg once daily
Carvedilol at a dose of 6.25 mg (Carvipress 6.25 mg®, Global Napi Pharmaceuticals, Egypt)
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.
Other Names:
  • Carvipress 6.25 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Management of arterial hypertension
Time Frame: 3 month
by measuring Systolic and diastolic blood pressure (mmHg)
3 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Effects Monitoring
Time Frame: 3 months
Adverse effects including headache, gastrointestinal disorders, weakness, shortness of breath, and hyperglycemia will be recorded.
3 months

Collaborators and Investigators

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

Sponsor

Kafrelsheikh University

Investigators

  • Principal Investigator: Mai Tarek Hamed, BSc (Pharmacy), Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
  • Study Director: Ahmed A Ali, 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

Helpful Links

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 1, 2024

Primary Completion (Actual)

March 1, 2025

Study Completion (Actual)

June 1, 2025

Study Registration Dates

First Submitted

January 20, 2026

First Submitted That Met QC Criteria

February 4, 2026

First Posted (Actual)

February 9, 2026

Study Record Updates

Last Update Posted (Actual)

February 9, 2026

Last Update Submitted That Met QC Criteria

February 4, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KFSIRB200-126

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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