Pharmacogenetic Dosing of Warfarin

• ClinicalTrials.gov Identifier: NCT02065388
• Recruitment Status: Completed
• First Posted: February 19, 2014
• Last Update Posted: February 19, 2014
• Sponsor: Academia Sinica, Taiwan
• Collaborators: Chang Gung Memorial Hospital; China Medical University Hospital; Kaohsiung Medical University
• Information provided by (Responsible Party): Academia Sinica, Taiwan

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Stroke; Venous Thrombosis; Atrial Fibrillation; Atrial Flutter	Behavioral: Standard of care dosing for warfarin; Genetic: Genotype-guided dosingTaiwan algorithm for warfarin; Genetic: Genotype-guided dosing IWPC algorithm for warfarin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: September 2009
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: December 2013

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Standard of care dosing for warfarin; 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).	Behavioral: Standard of care dosing for warfarin
Experimental: Genotype-guided dosingTaiwan algorithm for warfarin; 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).	Genetic: Genotype-guided dosingTaiwan algorithm for warfarin
Experimental: Genotype-guided dosing IWPC algorithm for warfarin; 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).	Genetic: Genotype-guided dosing IWPC algorithm for warfarin

Outcome Measures

Primary Outcome Measures :

1. Time spent in target INR range [ Time Frame: first month of therapy ]
   time spent in target INR range Time in the target INR Range will be the primary endpoints because of its strong association with adverse events: patients with subtherapeutic INR values are at increased risk of thrombosis and patients with high INR values are at increased risk of hemorrhage during warfarin treatment initiation.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Taiwan

Kaohsiung Medical University

Kaohsiung, Taiwan, 807

China Medical University Hospital

Taichung, Taiwan, 404

Chang Gung Memorial Hospital

Taoyuan, Taiwan, 333

Sponsors and Collaborators

Academia Sinica, Taiwan

Chang Gung Memorial Hospital

China Medical University Hospital

Kaohsiung Medical University

Investigators

• Principal Investigator: Ming Ta Michael Lee, PhD; Institute of Biomedical Sciences, Academia Sinica

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ohara M, Takahashi H, Lee MT, Wen MS, Lee TH, Chuang HP, Luo CH, Arima A, Onozuka A, Nagai R, Shiomi M, Mihara K, Morita T, Chen YT. Determinants of the over-anticoagulation response during warfarin initiation therapy in Asian patients based on population pharmacokinetic-pharmacodynamic analyses. PLoS One. 2014 Aug 22;9(8):e105891. doi: 10.1371/journal.pone.0105891. eCollection 2014.

• Responsible Party: Academia Sinica, Taiwan
• ClinicalTrials.gov Identifier: NCT02065388 History of Changes
• Other Study ID Numbers: AS-IRB01-100070
• First Posted: February 19, 2014
• Last Update Posted: February 19, 2014
• Last Verified: February 2014

Additional relevant MeSH terms:

Warfarin; Atrial Fibrillation; Thrombosis; Venous Thrombosis; Atrial Flutter; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Embolism and Thrombosis; Vascular Diseases; Anticoagulants