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

NCT07397481 | Completed Phase 4 DMC

• 1 other identifier: KFSIRB200-126
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Liver Cirrhosis; Arterial Hypertension

Keywords

Liver Cirrhosis; Anti- Hypertensive Drugs; Portal Hypertension

Outcome Measures

Primary Outcomes (1)

• Management of arterial hypertension

  by measuring Systolic and diastolic blood pressure (mmHg)

  3 month

Secondary Outcomes (1)

• Adverse Effects Monitoring

  3 months

Study Arms (4)

• Group A (n = 10): Child-Pugh class A patients received nebivolol at a dose of 5 mg once daily.

ACTIVE COMPARATOR

Nebivolol at a dose of 5 mg (Nevilob 5 mg®, Marcyrl Pharmaceutical Industries, Egypt)

Drug: Nebivolol 5 mg

• Group B (n = 10): Child-Pugh class A patients received carvedilol at a dose of 12.5 mg once daily.

ACTIVE COMPARATOR

Carvedilol at a dose of 12.5 mg (Carvipress 12.5 mg®, Global Napi Pharmaceuticals, Egypt)

Drug: Carvedilol 12.5 mg

Group C (n = 10): Child-Pugh B patients received nebivolol 2.5 mg once daily

ACTIVE COMPARATOR

Nebivolol at a dose of 2.5 mg (Nevilob 2.5 mg®, Marcyrl Pharmaceutical Industries, Egypt)

Drug: Nebivolol 2.5 mg

Group D (n = 10): Child-Pugh B patients received carvedilol 6.25 mg once daily

ACTIVE COMPARATOR

Carvedilol at a dose of 6.25 mg (Carvipress 6.25 mg®, Global Napi Pharmaceuticals, Egypt)

Drug: Carvedilol 6.25 mg

Interventions

Nebivolol 5 mg DRUG

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.

Also known as: Nevilob 5mg

• Group A (n = 10): Child-Pugh class A patients received nebivolol at a dose of 5 mg once daily.

Carvedilol 12.5 mg DRUG

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.

Also known as: Carvipress 12.5 mg

• Group B (n = 10): Child-Pugh class A patients received carvedilol at a dose of 12.5 mg once daily.

Nebivolol 2.5 mg DRUG

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.

Also known as: Nevilob 2.5mg

Group C (n = 10): Child-Pugh B patients received nebivolol 2.5 mg once daily

Carvedilol 6.25 mg DRUG

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.

Also known as: Carvipress 6.25 mg

Group D (n = 10): Child-Pugh B patients received carvedilol 6.25 mg once daily

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: yes \> 18 years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kafrelsheikh University: lead

Study Sites (1)

Kafrelsheikh University

Cairo, Egypt, Egypt

Location

Related Publications (1)

• Li T, Ke W, Sun P, Chen X, Belgaumkar A, Huang Y, Xian W, Li J, Zheng Q. Carvedilol for portal hypertension in cirrhosis: systematic review with meta-analysis. BMJ Open. 2016 May 4;6(5):e010902. doi: 10.1136/bmjopen-2015-010902.

  PMID: 27147389 BACKGROUND

Related Links

• Carvedilol for portal hypertension in cirrhosis: systematic review with meta-analysis

MeSH Terms

Conditions

Liver Cirrhosis; Hypertension; Hypertension, Portal

Interventions

Nebivolol; Carvedilol

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Propanolamines; Propanols; Carbazoles; Indoles; Heterocyclic Compounds, 3-Ring

Study Officials

• Mai Tarek Hamed, BSc (Pharmacy)

  Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University

  PRINCIPAL INVESTIGATOR

• Ahmed A Ali, PhD

  Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: assistant lecturer

Study Record Dates

• First Submitted: January 20, 2026
• First Posted: February 9, 2026
• Study Start: March 1, 2024
• Primary Completion: March 1, 2025
• Study Completion: June 1, 2025
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

EG (1)