Clinical Application of Simcyp-Guided Warfarin Initiation Doses in Cirrhotic Patients With Portal Vein Thrombosis

April 30, 2026 updated by: Naira Galal, Kafrelsheikh University

Dose Prediction for Statins and Anticoagulant Medications in Cirrhotic Patients Using Simcyp Program: Applications in Clinical Practice

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Cairo, Egypt
        • Kafrelsheikh University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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).
Drug: Warfarin 3 mg
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.
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).
Drug: Warfarin 2 mg
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Achieve Therapeutic INR
Time Frame: 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.
From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Average Warfarin Dose During Initiation Phase
Time Frame: From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
The mean daily warfarin dose required to achieve therapeutic anticoagulation during the 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
Time Frame: Within 3-5 days after warfarin initiation
The percentage of patients who achieved therapeutic INR (≥ 2.0) within 3 to 5 days after initiation of warfarin therapy.
Within 3-5 days after warfarin initiation
Follow-up Duration During Warfarin Initiation Phase
Time Frame: From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
The duration of patient follow-up during the warfarin initiation phase, measured in days.
From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
Incidence of Over-Anticoagulation
Time Frame: From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
The occurrence of excessive anticoagulation, defined as an international normalized ratio (INR) value greater than 4 during the initiation phase.
From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
Incidence of Bleeding Events
Time Frame: From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
The occurrence of bleeding complications during the study follow-up period, classified as minor or major according to standard clinical criteria.
From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
Incidence of Thromboembolic Events
Time Frame: From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)
The occurrence of any new thromboembolic events during the follow-up period after initiation of warfarin therapy.
From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kafrelsheikh University

Investigators

  • Study Director: Noha Mahmoud El-khodary, PhD, Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
  • Principal Investigator: Naira Galal, BSc Pharm, Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2024

Primary Completion (Actual)

March 15, 2025

Study Completion (Actual)

March 15, 2025

Study Registration Dates

First Submitted

April 23, 2026

First Submitted That Met QC Criteria

April 30, 2026

First Posted (Actual)

May 6, 2026

Study Record Updates

Last Update Posted (Actual)

May 6, 2026

Last Update Submitted That Met QC Criteria

April 30, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KFSIRB200-127-B
  • KFSIRB200-127 (Registry Identifier: Kafrelsheikh University IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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