StrokePhase 3NCT02065388
Pharmacogenetic Dosing of Warfarin
A Phase 3 study testing Genotype-guided dosingTaiwan algorithm for warfarin and Genotype-guided dosing IWPC algorithm for warfarin in people with Stroke and Venous Thrombosis, run by Academia Sinica, Taiwan at 3 sites in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Stroke, Venous Thrombosis, Atrial Fibrillation
- What is being tested?
- Genotype-guided dosingTaiwan algorithm for warfarin and Genotype-guided dosing IWPC algorithm for warfarin
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 3 sitesTaiwan
- Study dates
- Sep 2009to Dec 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
3 sites in 1 country.
Taiwan3 sites
Kaohsiung Medical University
Kaohsiung City, 807
China Medical University Hospital
Taichung, 404
Chang Gung Memorial Hospital
Taoyuan, 333
About this study
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.
Read more
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
- Being tested
- Standard of care dosing for warfarin, Genotype-guided dosingTaiwan algorithm for warfarin, Genotype-guided dosing IWPC algorithm for warfarin
- Medical subject headings
- Stroke, Venous Thrombosis, Atrial Fibrillation, Atrial Flutter
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of care dosing for warfarinBehavioural
Genotype-guided dosingTaiwan algorithm for warfarinGenetic
Genotype-guided dosing IWPC algorithm for warfarinGenetic
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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). Receives: Genetic: Genotype-guided dosing IWPC algorithm for warfarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: first month of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2014 (estimated)
- Study startSep 2009
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Academia Sinica, Taiwan
- Sponsor type
- University, hospital or other
- Collaborators
- Chang Gung Memorial Hospital, China Medical University Hospital, Kaohsiung Medical University
- Responsible party
- Sponsor
- Investigators
- Ming Ta Michael Lee, PhD, Principal investigator, Institute of Biomedical Sciences, Academia Sinica
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02065388
- Sponsor's protocol ID
- AS-IRB01-100070
- Status last verified
- Feb 2014
- First submitted
- 9 Feb 2014
- Last updated
- 19 Feb 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25148255
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenetic Dosing of Warfarin
- ClinicalTrials.gov ID
- NCT02065388
- Acronym / sponsor ID
- AS-IRB01-100070
- Conditions
- Stroke, Venous Thrombosis, Atrial Fibrillation, Atrial Flutter
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Academia Sinica, TaiwanUniversity, hospital or other
- Collaborators
- Chang Gung Memorial Hospital, China Medical University Hospital, Kaohsiung Medical University
- Study start
- Sep 2009
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 19 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Standard of care dosing for warfarin | Active comparator | Behavioral: Standard of care dosing for warfarinLoading dose (5mg) of warfarin for the first 3 days of treatment. Dose adjustment after initiation will using guideline modified from Tait el al. (1998). |
| Genotype-guided dosingTaiwan algorithm for warfarin | Experimental | Genetic: Genotype-guided dosingTaiwan algorithm for warfarinInitial 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). |
| Genotype-guided dosing IWPC algorithm for warfarin | Experimental | Genetic: Genotype-guided dosing IWPC algorithm for warfarinInitial 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). |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard of care dosing for warfarin | Behavioural | 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 |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2014.
- Derived from this study: PubMed 25148255Ohara 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ming Ta Michael Lee, PhD principal investigator
Institute of Biomedical Sciences, Academia Sinica
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Genotype-guided dosingTaiwan algorithm for warfarin and Genotype-guided dosing IWPC algorithm for warfarin in people with Stroke and Venous Thrombosis, run by Academia Sinica, Taiwan at 3 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time spent in target INR range (time frame: first month of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02065388, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2014.