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

Kafrelsheikh University

Status and phase: Completed; Phase 4

Conditions: Liver Cirrhosis; Arterial Hypertension

Treatments: Drug: Carvedilol 12.5 mg; Drug: Nebivolol 5 mg; Drug: Nebivolol 2.5 mg; Drug: Carvedilol 6.25 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT07397481

KFSIRB200-126

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 4 patient groups

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

Active Comparator group

Description:

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

Treatment:

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 group

Description:

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

Treatment:

Drug: Carvedilol 12.5 mg

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

Active Comparator group

Description:

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

Treatment:

Drug: Nebivolol 2.5 mg

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

Active Comparator group

Description:

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

Treatment:

Drug: Carvedilol 6.25 mg