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
- 21
- 试验地点
- 1
- 主要终点
- Time to Achieve Therapeutic INR
研究概览
简要总结
This was a prospective, open-label, pilot interventional clinical study conducted on Egyptian patients with liver cirrhosis complicated by portal vein thrombosis (PVT) who were indicated for anticoagulation therapy. The study aimed to evaluate the clinical applicability of Simcyp®-guided warfarin initiation doses according to Child-Pugh class, focusing on the time required to achieve a therapeutic INR and the safety of anticoagulation during the initiation phase.
详细描述
This was a prospective, open-label, pilot interventional clinical study conducted on adult cirrhotic patients with radiologically confirmed portal vein thrombosis. A total of twenty-one patients were enrolled from the outpatient clinics of the Hepatology, Gastroenterology, and Infectious Diseases Department at Kafrelsheikh University Hospital between March 2024 and March 2025.
Before initiation of anticoagulation therapy, all participants underwent comprehensive baseline clinical and laboratory assessments, including detailed medical history with emphasis on bleeding and thrombotic risk, physical examination, complete blood count, liver and renal function tests, and baseline coagulation profile. Eligible patients were classified according to Child-Pugh score into class A or B.
Patients with Child-Pugh class A (n = 10) received warfarin 3 mg once daily, while patients with Child-Pugh class B (n = 11) received warfarin 2 mg once daily. Initial dosing was guided by Simcyp® model predictions and the closest commercially available strengths. Enoxaparin was administered as bridging therapy at a therapeutic dose of 1 mg/kg twice daily until achievement of the target INR.
During the warfarin initiation phase, daily INR monitoring was performed, and dose adjustments were carried out using standardized clinical titration principles until a stable therapeutic INR (2.0-3.0) was achieved on two consecutive measurements. Patients were closely monitored throughout the follow-up period for treatment-related adverse events, with particular emphasis on bleeding complications. Bleeding events were systematically assessed and classified as minor or major, in addition to monitoring for any thromboembolic events.
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
- •Age ≥ 18 years
- •Diagnosed liver cirrhosis (Child-Pugh A or B)
- •Radiologically confirmed portal venous thrombosis
- •No prior exposure to warfarin (for initial dose simulation)
- •No pervious history of variceal bleeding
排除标准
- •Child-Pugh C cirrhosis
- •Platelets < 50,000/mm³
- •Severe renal impairment (eGFR < 30 mL/min)
- •Use of strong CYP2C9/CYP3A4 inhibitors or inducers
- •Pregnancy or breastfeeding
- •Active malignancy, especially hepatocellular carcinoma
研究组 & 干预措施
Child-Pugh Class A (n = 10)
Adult cirrhotic patients with portal vein thrombosis received 3 mg warfarin oral once daily (Marevan® 3 mg, GSK, Egypt) Other Intervention (Bridging Therapy): Enoxaparin (1 mg/kg) subcutaneously twice daily until achievement of a stable therapeutic INR (2.0-3.0).
干预措施: Warfarin 3 mg (Drug)
Child-Pugh Class B (n = 11)
Adult cirrhotic patients with portal vein thrombosis received 2 mg warfarin oral once daily (2 tablets of Marevan® 1 mg, GSK, Egypt).
Other Intervention (Bridging Therapy): Enoxaparin (1 mg/kg) subcutaneously twice daily until achievement of a stable therapeutic INR (2.0-3.0).
干预措施: Warfarin 2 mg (Drug)
结局指标
主要结局
Time to Achieve Therapeutic INR
时间窗: From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
The number of days from initiation of warfarin therapy until an INR value within the therapeutic range (≥ 2.0) was documented.
次要结局
- Average Warfarin Dose During Initiation Phase(From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days))
- Proportion of Patients Achieving Therapeutic INR Within 3-5 Days(Within 3-5 days after warfarin initiation)
- Follow-up Duration During Warfarin Initiation Phase(From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days))
- Incidence of Over-Anticoagulation(From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days))
- Incidence of Bleeding Events(From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days))
- Incidence of Thromboembolic Events(From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days))
研究者
Naira Galal
Assistant Lecturer
Kafrelsheikh University