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
연구 개요
상세 설명
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.
연구 유형
등록 (실제)
단계
- 4단계
연락처 및 위치
연구 장소
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Cairo, 이집트
- Kafrelsheikh University
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참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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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실험적: 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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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Time to Achieve Therapeutic INR
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Average Warfarin Dose During Initiation Phase
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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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공동 작업자 및 조사자
수사관
- 연구 책임자: Noha Mahmoud El-khodary, PhD, Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
- 수석 연구원: Naira Galal, BSc Pharm, Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
간행물 및 유용한 링크
일반 간행물
- 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.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- KFSIRB200-127-B
- KFSIRB200-127 (레지스트리 식별자: Kafrelsheikh University IRB)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
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