Dose Prediction for Statins and Anticoagulant Medications in Cirrhotic Patients Using Simcyp Program: Applications in Clinical Practice
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Change in Portal Vein Diameter (mm)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients aged ≥ 18 years
- •Confirmed diagnosis of liver cirrhosis (clinical, laboratory, or imaging evidence)
- •Evidence of portal hypertension (clinical findings and/or Doppler ultrasound measurements)
- •No previous history of variceal bleeding
- •Child-Pugh class A or B
排除标准
- •Active hepatocellular carcinoma
- •Severe renal impairment (eGFR < 30 mL/min/1.73 m²)
- •Baseline creatine kinase (CK) > 3 × upper limit of normal
- •Known hypersensitivity to simvastatin
- •Current therapy with strong CYP3A4 inhibitors
- •Any active malignancy in the last 2 years
- •Pregnancy or lactation
研究组 & 干预措施
Group 1_Child-Pugh A
10 patients with Child-Pugh A received Simvastatin 15 mg once daily.
干预措施: Simvastatin 15 mg (Drug)
Group 2_Child-Pugh B
12 patients with Child-Pugh B received Simvastatin 5 mg once daily.
干预措施: Simvastatin 5 mg (Drug)
结局指标
主要结局
Change in Portal Vein Diameter (mm)
时间窗: 3 months
Portal vein diameter will be measured as a Doppler ultrasound parameter to evaluate changes related to portal hypertension
Change in Portal Vein Velocity (cm/s)
时间窗: 3 months
Portal vein velocity will be assessed as an indicator reflecting changes in portal hypertension
Change in Hepatic Artery Resistance Index (HARI)
时间窗: 3 months
The Hepatic Artery Resistance Index will be measured as a Doppler-based marker associated with changes in portal hypertension
Change in Congestion Index (CI) (cm/ [cm/s2])
时间窗: 3 months
The congestion index will be evaluated as a Doppler-derived surrogate marker for portal hypertension severity
Change in Modified Vascular Liver Index (MVLI) (cm/s)
时间窗: 3 months
MVLI will be measured as part of the Doppler assessment reflecting changes in portal hypertension
Change in Platelet Count (×10⁹/L)
时间窗: 3 months
Platelet count will be assessed as a hematologic surrogate marker associated with portal hypertension.
次要结局
- Incidence of adverse effects related to Simvastatin(3 months)
研究者
Naira Galal
assistant lecturer
Kafrelsheikh University