Pharmacogenetic Dosing of Warfarin

NCT02065388 | Completed Phase 3 DMC

• 1 other identifier: AS-IRB01-100070
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 3

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.

Conditions

Stroke; Venous Thrombosis; Atrial Fibrillation; Atrial Flutter

Outcome Measures

Primary Outcomes (1)

• Time spent in target INR range

  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.

  first month of therapy

Study Arms (3)

Standard of care dosing for warfarin

ACTIVE COMPARATOR

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

Genotype-guided dosingTaiwan algorithm for warfarin

EXPERIMENTAL

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

Genotype-guided dosing IWPC algorithm for warfarin

EXPERIMENTAL

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

Interventions

Standard of care dosing for warfarin BEHAVIORAL

Standard of care dosing for warfarin

Genotype-guided dosingTaiwan algorithm for warfarin GENETIC

Genotype-guided dosingTaiwan algorithm for warfarin

Genotype-guided dosing IWPC algorithm for warfarin GENETIC

Genotype-guided dosing IWPC algorithm for warfarin

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Academia Sinica, Taiwan: lead
• Chang Gung Memorial Hospital: collaborator
• China Medical University Hospital: collaborator
• Kaohsiung Medical University: collaborator

Study Sites (3)

Kaohsiung Medical University

Kaohsiung City, 807, Taiwan

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

Chang Gung Memorial Hospital

Taoyuan District, 333, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 25148255 DERIVED

MeSH Terms

Conditions

Stroke; Venous Thrombosis; Atrial Fibrillation; Atrial Flutter

Interventions

Warfarin

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Thrombosis; Embolism and Thrombosis; Arrhythmias, Cardiac; Heart Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ming Ta Michael Lee, PhD

  Institute of Biomedical Sciences, Academia Sinica

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2014
• First Posted: February 19, 2014
• Study Start: September 1, 2009
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: February 19, 2014

Record last verified: 2014-02

Locations

TW (3)