Atrial FibrillationPhase 4NCT01610141
Applying Pharmacogenetics to Warfarin Dosing in Chinese Patients
A Phase 4 study testing Genotype-guided warfarin dosing and Non-genotype guided warfarin dosing in people with Atrial Fibrillation and Deep Vein Thrombosis, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
The purpose of this study is to determine whether pharmacogenetic guided dosing of warfarin is promising for the improvement of efficiency, therapeutic efficacy, and, especially, safety of warfarin therapy than a dosing regimen without the pharmacogenetic information in Chinese patients initiated on warfarin… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Atrial Fibrillation, Deep Vein Thrombosis, Pulmonary Embolism
- What is being tested?
- Genotype-guided warfarin dosing and Non-genotype guided warfarin dosing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 1 siteChina
- Study dates
- Jun 2012to Jun 2015
- Phase
- Phase 4
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥18 years old
- Patients initiated on warfarin for venous thromboembolism, pulmonary embolism, atrial fibrillation or heart valve replacement that require long- term oral anticoagulation with target INR ranged 1.5-3.0 for at least 3 months
- Ability to attend scheduled visits
- Signed informed consent
Who cannot join
- Non-eligible subject
- Pregnant,lactating or of child-bearing potential women
- Patients with severe co-morbidities (e.g., renal insufficiency/creatinine > 2.5 mg/dL,hepatic insufficiency, active malignancy, terminal disease)
- Known genotype CYP2C9 or VKORC1 at start of the study
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Institute of geriatric Cardiology, General Hospital of People's Liberation Army
Beijing, 100853
Tong Yin, Dr., 86-13693693085, yintong2000@yahoo.com
Xiaoqi Li, Dr., 86-15901075996, xiaoqili_2012@126.com
About this study
The purpose of this study is to determine whether pharmacogenetic guided dosing of warfarin is promising for the improvement of efficiency, therapeutic efficacy, and, especially, safety of warfarin therapy than a dosing regimen without the pharmacogenetic information in Chinese patients initiated on warfarin anticoagulation.
Read the detailed description
Warfarin is the most widely used oral anticoagulation drug for preventing and treating thromboembolic events, but there is greater than 10-fold interindividual variability in the dose required to attain a therapeutic response. In 2007, the US Food and Drug Administration updated the label of warfarin, recommending consideration of pharmacogenetic information which has been confirmed to contribute significantly to the variability in warfarin dose requirements. Thereafter, multiple pharmacogenetic dosing algorithms were constructed to predict warfarin dose by integrating clinical and genetic factors. Taken together, approximately between one-third and one- half of the variability in warfarin dose could be explained by the proposed algorithms. However, the potential benefit of these dosing algorithms in terms of their safety and clinical utility has not been adequately investigated in randomised settings in Chinese patients.
Study objectives:
- To apply routine pharmacogenetic (PG)-guided dosing of warfarin in clinical practice in Chinese patients.
- To compare the percentage out-of-range (%OOR) International Normalized Ratios (INRs) during the first 3 month of warfarin therapy using PG-guided dosing with historical standard (STD), empiric dosed controls.
- To compare the cost effectiveness, number of thromboembolic and bleeding events, time within therapeutic INR range, time to reach stable dose and number of supratherapeutic INR peaks during the first 3 month of warfarin therapy using PG-guided dosing with historical standard (STD), empiric dosed controls.
Study design:
This is a prospective, randomized study of Chinese patients who are to initiate chronic warfarin anticoagulation for specific, qualifying clinical reasons (i.e., atrial fibrillation, Deep vein thrombosis/pulmonary embolism, or Prosthetic valve replacement). Qualifying patients will be consented and randomized to an individualized, pharmacogenetic guided warfarin-dosing regimen (PG group) or to standard care (without knowledge of genotype)(STD group). All patients will receive a baseline INR. For patients in PG group, a maintenance dose for each patient will be predicted by the pharmacogenetic algorithm derived previously in Chinese. A maintenance dose of 3 mg/day will designed to each patients in STD group. The starting dose of warfarin that is twice the assigned daily maintenance dose will be prescribed on the first and second days, and then the dose will revert to the assigned maintenance dose.
Study duration:
Each patient will participate for at least 3 months.
- Being tested
- Genotype-guided warfarin dosing, Non-genotype guided warfarin dosing
- Keywords
- warfarin metabolism, pharmacogenetics, CYP2C9, genotyping, VKORC1, CYP4F2, anticoagulation, atrial fibrillation, deep vein thrombosis, pulmonary embolism, Artificial Heart Valve
- Medical subject headings
- Atrial Fibrillation, Venous Thrombosis, Pulmonary Embolism, Heart Valve Diseases, Vitamin K-Dependent Clotting Factors, Combined Deficiency Of, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genotype-guided warfarin dosingOther
Applying a Pharmacogenetic-guided warfarin dosing algorithm derived from Chinese to determine the daily maintenance dose of warfarin, based on clinical factors (age, sex, body surface area, etc.), and VKORC1, CYP2C9 and CYP4F2 genotypes, to individualize the dosing of warfarin.
Non-genotype guided warfarin dosingOther
A Empiric fixed warfarin dose of 3 mg/day was given to the patients for at least 3 days. Following doses were adjusted according to the INR measurement.
| Study group | Role | What they receive |
|---|---|---|
| Genotype-guided warfarin dosing | Experimental | A pharmacogenetic dosing algorithm including clinical factors and genotype information (VKORC1, CYP2C9 and CYP4F2) will be used to determine warfarin doses. Receives: Other: Genotype-guided warfarin dosing |
| Non-genotype guided warfarin dosing | Active comparator | A fixed warfarin dose of 3 mg/day was given to the patients for at least 3 days. Following doses were adjusted according to the INR measurement. Receives: Other: Non-genotype guided warfarin dosing |
What is being measured
The primary outcome is the main question the study is designed to answer.
A comparison between the pharmacogenetic and standard arms of the per-patient percentage of out-of-range INRs (<1.5, >3).
Measured: 3 months
Secondary outcomes (8)
Time to the first supratherapeutic INR
Measured: 3 months
The proportion of time within the therapeutic INR range
Measured: 3 months
The proportion of patients reaching therapeutic INR on days 5 and 8
Measured: 3 months
The total number of INR measurements and number of dose adjustments made
Measured: 3 months
Proportion of INRs > 4
Measured: 3 months
Major bleeding events
Measured: 3 months
Minor bleeding events
Measured: 3 months
Thromboembolic complications
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2012 (estimated)
- Study startJun 2012
- Primary completionJun 2014 (estimated)
- Study completionJun 2015 (estimated)
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 Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tong Yin, Chinese PLA General Hospital
- Investigators
- Tong Yin, Dr., Principal investigator, Institute of Geriatric Cardiology, General Hospital of People's Liberation Army, Beijing China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01610141
- Sponsor's protocol ID
- NSFC-30971259
- Status last verified
- Oct 2013
- First submitted
- 30 May 2012
- Last updated
- 9 Oct 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Liu Y, Yang J, Xu Q, Xu B, Gao L, Zhang Y, Zhang Y, Wang H, Lu C, Zhao Y, Yin T. Comparative performance of warfarin pharmacogenetic algorithms in Chinese patients. Thromb Res. 2012 Sep;130(3):435-40. doi: 10.1016/j.thromres.2012.02.003. Epub 2012 Feb 27.
PubMed 22374335
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Applying Pharmacogenetics to Warfarin Dosing in Chinese Patients
- ClinicalTrials.gov ID
- NCT01610141
- Acronym / sponsor ID
- NSFC-30971259
- Keywords
- warfarin metabolism, pharmacogenetics, CYP2C9, genotyping, VKORC1, CYP4F2, anticoagulation, atrial fibrillation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- Jun 2014 (estimated)
- Study completion
- Jun 2015 (estimated)
- First posted
- 1 Jun 2012 (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.
The purpose of this study is to determine whether pharmacogenetic guided dosing of warfarin is promising for the improvement of efficiency, therapeutic efficacy, and, especially, safety of warfarin therapy than a dosing regimen without the pharmacogenetic information in Chinese patients initiated on warfarin anticoagulation.
Detailed description
Warfarin is the most widely used oral anticoagulation drug for preventing and treating thromboembolic events, but there is greater than 10-fold interindividual variability in the dose required to attain a therapeutic response. In 2007, the US Food and Drug Administration updated the label of warfarin, recommending consideration of pharmacogenetic information which has been confirmed to contribute significantly to the variability in warfarin dose requirements. Thereafter, multiple pharmacogenetic dosing algorithms were constructed to predict warfarin dose by integrating clinical and genetic factors. Taken together, approximately between one-third and one- half of the variability in warfarin dose could be explained by the proposed algorithms. However, the potential benefit of these dosing algorithms in terms of their safety and clinical utility has not been adequately investigated in randomised settings in Chinese patients.
Study objectives:
- To apply routine pharmacogenetic (PG)-guided dosing of warfarin in clinical practice in Chinese patients.
- To compare the percentage out-of-range (%OOR) International Normalized Ratios (INRs) during the first 3 month of warfarin therapy using PG-guided dosing with historical standard (STD), empiric dosed controls.
- To compare the cost effectiveness, number of thromboembolic and bleeding events, time within therapeutic INR range, time to reach stable dose and number of supratherapeutic INR peaks during the first 3 month of warfarin therapy using PG-guided dosing with historical standard (STD), empiric dosed controls.
Study design:
This is a prospective, randomized study of Chinese patients who are to initiate chronic warfarin anticoagulation for specific, qualifying clinical reasons (i.e., atrial fibrillation, Deep vein thrombosis/pulmonary embolism, or Prosthetic valve replacement). Qualifying patients will be consented and randomized to an individualized, pharmacogenetic guided warfarin-dosing regimen (PG group) or to standard care (without knowledge of genotype)(STD group). All patients will receive a baseline INR. For patients in PG group, a maintenance dose for each patient will be predicted by the pharmacogenetic algorithm derived previously in Chinese. A maintenance dose of 3 mg/day will designed to each patients in STD group. The starting dose of warfarin that is twice the assigned daily maintenance dose will be prescribed on the first and second days, and then the dose will revert to the assigned maintenance dose.
Study duration:
Each patient will participate for at least 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Genotype-guided warfarin dosing | Experimental | Other: Genotype-guided warfarin dosingA pharmacogenetic dosing algorithm including clinical factors and genotype information (VKORC1, CYP2C9 and CYP4F2) will be used to determine warfarin doses. |
| Non-genotype guided warfarin dosing | Active comparator | Other: Non-genotype guided warfarin dosingA fixed warfarin dose of 3 mg/day was given to the patients for at least 3 days. Following doses were adjusted according to the INR measurement. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients ≥18 years old
- Patients initiated on warfarin for venous thromboembolism, pulmonary embolism, atrial fibrillation or heart valve replacement that require long- term oral anticoagulation with target INR ranged 1.5-3.0 for at least 3 months
- Ability to attend scheduled visits
- Signed informed consent
Key exclusion criteria (4 listed)
- Non-eligible subject
- Pregnant,lactating or of child-bearing potential women
- Patients with severe co-morbidities (e.g., renal insufficiency/creatinine > 2.5 mg/dL,hepatic insufficiency, active malignancy, terminal disease)
- Known genotype CYP2C9 or VKORC1 at start of the study
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 |
|---|---|---|
| Genotype-guided warfarin dosingApplying a Pharmacogenetic-guided warfarin dosing algorithm derived from Chinese to determine the daily maintenance dose of warfarin, based on clinical factors (age, sex, body surface area, etc.), and VKORC1, CYP2C9 and CYP4F2 genotypes, to individualize the dosing of warfarin. | Other | Genotype-guided warfarin dosing |
| Non-genotype guided warfarin dosingA Empiric fixed warfarin dose of 3 mg/day was given to the patients for at least 3 days. Following doses were adjusted according to the INR measurement. | Other | Non-genotype guided warfarin dosing |
Primary outcome
A comparison between the pharmacogenetic and standard arms of the per-patient percentage of out-of-range INRs (<1.5, >3).
Time frame: 3 months
8 secondary outcomes
Time to the first supratherapeutic INR
Time frame: 3 months
The proportion of time within the therapeutic INR range
Time frame: 3 months
The proportion of patients reaching therapeutic INR on days 5 and 8
Time frame: 3 months
The total number of INR measurements and number of dose adjustments made
Time frame: 3 months
Proportion of INRs > 4
Time frame: 3 months
Major bleeding events
Time frame: 3 months
Minor bleeding events
Time frame: 3 months
Thromboembolic complications
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2013.
- Background: PubMed 22374335Liu Y, Yang J, Xu Q, Xu B, Gao L, Zhang Y, Zhang Y, Wang H, Lu C, Zhao Y, Yin T. Comparative performance of warfarin pharmacogenetic algorithms in Chinese patients. Thromb Res. 2012 Sep;130(3):435-40. doi: 10.1016/j.thromres.2012.02.003. Epub 2012 Feb 27.
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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.
Tong Yin, Dr. principal investigator
Institute of Geriatric Cardiology, General Hospital of People's Liberation Army, Beijing China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Genotype-guided warfarin dosing and Non-genotype guided warfarin dosing in people with Atrial Fibrillation and Deep Vein Thrombosis, run by Chinese PLA General Hospital at 1 site in China.
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 4 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 9 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tong Yin, Dr. (86-13693693085, yintong2000@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A comparison between the pharmacogenetic and standard arms of the per-patient percentage of out-of-range INRs (<1.5, >3). (time frame: 3 months). 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 NCT01610141, 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 9 Oct 2013.