Clinical Application of Simcyp-Guided Warfarin Initiation Doses in Cirrhotic Patients With Portal Vein Thrombosis
Dose Prediction for Statins and Anticoagulant Medications in Cirrhotic Patients Using Simcyp Program: Applications in Clinical Practice
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ 4
連絡先と場所
研究場所
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Cairo、エジプト
- Kafrelsheikh University
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：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).
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Warfarin is a vitamin K antagonist approved for the treatment of thromboembolic disorders and was used in this study for anticoagulation in cirrhotic patients with portal vein thrombosis.
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実験的：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). |
Warfarin is a vitamin K antagonist approved for the treatment of thromboembolic disorders and was used in this study for anticoagulation in cirrhotic patients with portal vein thrombosis.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Time to Achieve Therapeutic INR
時間枠：From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
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The number of days from initiation of warfarin therapy until an INR value within the therapeutic range (≥ 2.0) was documented.
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From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Average Warfarin Dose During Initiation Phase
時間枠：From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
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The mean daily warfarin dose required to achieve therapeutic anticoagulation during the initiation phase.
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From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
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Proportion of Patients Achieving Therapeutic INR Within 3-5 Days
時間枠：Within 3-5 days after warfarin initiation
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The percentage of patients who achieved therapeutic INR (≥ 2.0) within 3 to 5 days after initiation of warfarin therapy.
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Within 3-5 days after warfarin initiation
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Follow-up Duration During Warfarin Initiation Phase
時間枠：From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
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The duration of patient follow-up during the warfarin initiation phase, measured in days.
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From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
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Incidence of Over-Anticoagulation
時間枠：From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
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The occurrence of excessive anticoagulation, defined as an international normalized ratio (INR) value greater than 4 during the initiation phase.
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From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
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Incidence of Bleeding Events
時間枠：From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
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The occurrence of bleeding complications during the study follow-up period, classified as minor or major according to standard clinical criteria.
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From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
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Incidence of Thromboembolic Events
時間枠：From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
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The occurrence of any new thromboembolic events during the follow-up period after initiation of warfarin therapy.
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From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
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協力者と研究者
スポンサー
捜査官
- スタディディレクター：Noha Mahmoud El-khodary, PhD、Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
- 主任研究者：Naira Galal, BSc Pharm、Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
出版物と役立つリンク
一般刊行物
- Guerrero A, Campo LD, Piscaglia F, Scheiner B, Han G, Violi F, Ferreira CN, Tellez L, Reiberger T, Basili S, Zamora J, Albillos A; Baveno Cooperation: an EASL consortium. Anticoagulation improves survival in patients with cirrhosis and portal vein thrombosis: The IMPORTAL competing-risk meta-analysis. J Hepatol. 2023 Jul;79(1):69-78. doi: 10.1016/j.jhep.2023.02.023. Epub 2023 Feb 28.
- Davis JPE, Lim JK, Francis FF, Ahn J. AGA Clinical Practice Update on Management of Portal Vein Thrombosis in Patients With Cirrhosis: Expert Review. Gastroenterology. 2025 Feb;168(2):396-404.e1. doi: 10.1053/j.gastro.2024.10.038. Epub 2024 Dec 20.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- KFSIRB200-127-B
- KFSIRB200-127 (レジストリ識別子：Kafrelsheikh University IRB)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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