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
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 4
Contactos e Locais
Locais de estudo
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Cairo, Egito
- Kafrelsheikh University
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: 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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Experimental: 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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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Time to Achieve Therapeutic INR
Prazo: 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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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Average Warfarin Dose During Initiation Phase
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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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Colaboradores e Investigadores
Patrocinador
Investigadores
- Diretor de estudo: Noha Mahmoud El-khodary, PhD, Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
- Investigador principal: Naira Galal, BSc Pharm, Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
Publicações e links úteis
Publicações Gerais
- 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.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Processos Patológicos
- Doenças do aparelho digestivo
- Doenças do Fígado
- Fibrose
- Condições Patológicas, Sinais e Sintomas
- Cirrose hepática
- Compostos heterocíclicos, 1 anel
- Compostos heterocíclicos
- Compostos heterocíclicos, 2 anel
- Compostos heterocíclicos, anel fundido
- Pyrans
- Coumarins
- Benzopyrans
- 4-hidroxicoumarinas
- Varfarina
Outros números de identificação do estudo
- KFSIRB200-127-B
- KFSIRB200-127 (Identificador de registro: Kafrelsheikh University IRB)
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