Pharmacogenetic Dosing of Warfarin

Academia Sinica, Taiwan

Status and phase: Completed; Phase 3

Conditions: Atrial Flutter; Atrial Fibrillation; Stroke; Venous Thrombosis

Treatments: Behavioral: Standard of care dosing for warfarin; Genetic: Genotype-guided dosing IWPC algorithm for warfarin; Genetic: Genotype-guided dosingTaiwan algorithm for warfarin

Study type: Interventional

Funder types: Other

Identifiers

NCT02065388

AS-IRB01-100070

Details and patient eligibility

About

Purpose:

Warfarin is now the most commonly used oral anticoagulant. This drug has inter-individual variability due to the genetic polymorphisms in the warfarin metabolizing enzyme, CYP2C9 and warfarin target, VKORC1. The investigators' team developed a pharmacogenetic dosing algorithm which can predict patients required warfarin dose, thus could prevent warfarin induced warfarin adverse events.

Methods:

The investigators recruited patients with indications for warfarin, the genotypes of VKORC1 and CYP2C9 were determined by the hospitals and verified by National Center for Genome Medicine. The investigators then randomized the patients to one of three arms: 1. Warfarin dose predicted by dosing algorithm developed by the International Warfarin pharmacogenetic Consortium (IWPC), 2. Algorithm developed by the Taiwan Warfarin Consortium and 3. Standard of care. The investigators aimed to determine whether using genetic dosing algorithm can lead to more stable dose and safer use of the drug.

Enrollment: 300 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients must give their informed consent and complete the case report form.
• Patients must be over the age of 20.
• Patients have clinical indications for warfarin therapy but do not have any prior warfarin treatment.

Exclusion criteria

• Patients who did not complete the informed consent form or the CRF
• Patients who are less than the age of 20.
• Patients who had prior or is currently on warfarin treatment.
• Patients who have hemorrhagic tendencies or hemorrhagic diseases defined as copious bleeding caused by viral or bacterial infections; cancer and hepatic dysfunction defined as GOP and GPT values three times higher than normal value
• Patients who has Vitamin K deficiency
• Female patients who is currently pregnant

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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300 participants in 3 patient groups

Standard of care dosing for warfarin

Active Comparator group

Description:

Loading dose (5mg) of warfarin for the first 3 days of treatment. Dose adjustment after initiation will using guideline modified from Tait el al. (1998).

Treatment:

Behavioral: Standard of care dosing for warfarin

Genotype-guided dosingTaiwan algorithm for warfarin

Experimental group

Description:

Initial loading dosing of warfarin for the first 3 days of treatment will be determined by the Taiwan algorithm that uses clinical and genetic information. Dose adjustment after initiation will using guideline modified from Tait el al. (1998).

Treatment:

Genetic: Genotype-guided dosingTaiwan algorithm for warfarin

Genotype-guided dosing IWPC algorithm for warfarin

Experimental group

Description:

Initial loading dosing of warfarin for the first 3 days of treatment will be determined by the IWPC algorithm that uses clinical and genetic information. Dose adjustment after initiation will using guideline modified from Tait el al. (1998).

Treatment:

Genetic: Genotype-guided dosing IWPC algorithm for warfarin