Heart Valve ProsthesisNCT03797534

Individualized Administration of Warfarin by Polymorphisms of VKORC1 and CYP2C9 Genes

A study testing dose regime in people with Heart Valve Prosthesis, run by Fujian Medical University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Trial summary

The purpose of this study is to explore the individualized administration model of warfarin suitable for Chinese people, and provide a scientific reference for the use of warfarin to Chinese people. Read more about this study

Who is it for?: Ages 14 years and older
Conditions the study is for: Heart Valve Prosthesis
What is being tested?: dose regime
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 600 participants
Where: 1 siteChina
Study dates: 1 Feb 2019to 1 Jan 2023
Phase: Interventional
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 14 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Age > 14 years old；
Warfarin anticoagulant therapy is required for at least 3 months；
The genotype of patient VKORC1 is non-AA, CYP2C9 genotype is non*1/*1； the patients who are followed up, regularly monitored for INR and willing to provide peripheral blood for DNA extraction and genetic testing；
The patient or family members can understand the research plan and will participate in this study and provide a written informed consent；

Who cannot join

Severe liver dysfunction (ChildPugh ≥ 10);
Severe infection, respiratory failure;
Severe heart failure ( NYHA ≥ IV);
Severe renal insufficiency (Ccr ≤ 20ml / min);
Cancer;
Diseases of the blood system;

Show all 17Show fewer

Severe pulmonary hypertension (PAPm ≥ 45mmHg);
Abnormal thyroid function;
Patients with a history of venous thromboembolism, or serious events such as severe bleeding or embolism;
Women who are pregnant or breastfeeding;
Taking or planning to take other oral anticoagulants;
The base INR value is >1.4;
VKORC1, CYP2C9 genotypes are AA, *1/*1;
Secondary valve replacement surgery;
Emergency hospital admission for valve surgery;
Diagnosis of coronary atherosclerotic heart disease;
Severe mental illness, mental disorder ; -

Trial locations and contacts

1 site in 1 country.

China1 site, 1 recruiting

the Department of Cardiovascular Surgery
Fuzhou, Fujian, 350001
Liang-Wan Chen, M.D Ph.D, 86 13358255333, 343983217@qq.com
Jin-Hua Zhang, Ph.D, 86 13609532263, pollyzhang2006@126.com
Recruiting

Other trials in China

About this study

Official title: Individualized Administration of Warfarin by Polymorphisms of VKORC1 and CYP2C9 Genes:A Randomized Controlled Trial, Multi-center Trial

The purpose of this study is to explore the individualized administration model of warfarin suitable for Chinese people, and provide a scientific reference for the use of warfarin to Chinese people.

Read the detailed description

About 600 patients with VKORC1 and CYP2C9 gene mutations were included in the treatment of warfarin anticoagulant therapy. The main indications include valve replacement, atrial fibrillation, pulmonary embolism, etc., randomly divided into 2 groups, respectively, the control group (that is, the use of fixed-dose group), Bayesian-model group, the use of single-blind treatment method, to evaluate the number of major adverse events, TTR and INR adjustments in patients between different groups after three months of taking warfarin, and then to explore the individualized drug use model of warfarin suitable for Chinese population.

In the Bayesian group, according to the genotype of VKORC1 and CYP2C9, the stable dose was calculated by the dose prediction model of Bayesian, and the first three drugs were taken at this dose, and then adjusted to the actual stable dose according to the change of INR. Meanwhile, the control group was administered according to the traditional way, that is, the initial dose is 2.5 or 3mg/d and is gradually adjusted to a stable dose according to changes of INR. The monitoring frequency of INR is: once a day from the beginning of the drug to the time of discharge, once a week after discharge, and once a month after the stable dose is obtained. Detailed records of the number of days to reach a stable dose, the INR value and the occurrence of side effects and time are documented. The concrete steps are as follows:

clinicians to judge the standard of the selection criteria;
to obtain the consent of the patient and sign an informed consent certificate;
to collect 2ml anticoagulant blood before the drug, fill in the application form for individualized drug use in warfarin, and indicate the experimental group and control group;
the specimen assigned to the laboratory for Genotyping;
lab to calculate the predicted stable warfarin dose and the results fed back to the clinician within one working day after receiving the specimen;
in the control group, the drug retained at the regular dose, and the first 3 days of the experimental group administered at the predicted dose;
the dosage of warfarin in the two groups of cases adjusted to the stable dose according to the value, and the adjustment amplitude of the experimental group also referred to the predicted stable dose.
to monitor INR once a day during hospitalization, and to those who do not receive a stable dose of discharge, follow up and monitor INR once a week until a stable dose or medication is obtained for 90 days;
to document clinical trial records, including the daily use of warfarin, each detection of the appearance of the situation like INR value, bleeding, venous embolism and other side effects.

Finally，according to the outcome parameters,statistical analysis were performed with SPSS 11.5 software. A value of P < 0.05 was considered statistically significant.

Conditions: Heart Valve Prosthesis
Being tested: dose regime
Keywords: warfarin, gene

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

dose regimeOther
The initial dose of the experimental group will be calculated by the Bayesian model.

Study groups in NCT03797534
Study group	Role	What they receive
Standard anticoagulant group	No intervention	Not described
Bayesian model group	Experimental	Not described Receives: Other: dose regime

What is being measured

The primary outcome is the main question the study is designed to answer.

excessive anticoagulant time ratio
INR>3，INR>4
Measured: 3 months postoperatively
The occurrence of primary bleeding events
gastrointestinal hemorrhage, intracerebral hemorrhage,etc
Measured: 3 months postoperatively
The occurance of secondary bleeding events
nasal bleeding, skin stasis,etc
Measured: 3 months postoperatively
The occurrence of thrombosis events
ischemic stroke, deep vein thrombosis,etc
Measured: 3 months postoperatively

Secondary outcomes (8)

Percentage of time in therapeutic range
Measured: 3 months, 6 months, 12 months postoperatively
The time required to reach the treatment target INR for the first time;
Measured: 3 months postoperatively
The time required from the beginning of treatment to the stable dose;
Measured: 3 months postoperatively
The percentage of time below the target INR range;
Measured: 3 months postoperatively
The percentage of time above the target INR range;
Measured: 3 months postoperatively
The number of dose adjustments and the number of INR measured during the first month of treatment;
Measured: 3 months postoperatively
The proportion of patients in each group receiving a stable dose after follow-up;
Measured: 3 months postoperatively
The proportion of patients in each group having side effects after follow-up
Measured: 3 months postoperatively

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Feb 20191 Jan 2023

First posted9 Jan 2019
Study start1 Feb 2019 (estimated)
Primary completion1 Jan 2022 (estimated)
Study completion1 Jan 2023 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Heart Valve ProsthesisStudies of the same condition, open and under way.
More trials run by Fujian Medical UniversityThe 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 N/A
Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Care provider
Enrolment: 600 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03797534
Sponsor's protocol ID: CLW2018WA
Status last verified: Jan 2019
First submitted: 6 Jan 2019
Last updated: 15 Jan 2019
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Gage BF, Eby C, Johnson JA, Deych E, Rieder MJ, Ridker PM, Milligan PE, Grice G, Lenzini P, Rettie AE, Aquilante CL, Grosso L, Marsh S, Langaee T, Farnett LE, Voora D, Veenstra DL, Glynn RJ, Barrett A, McLeod HL. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther. 2008 Sep;84(3):326-31. doi: 10.1038/clpt.2008.10. Epub 2008 Feb 27.
PubMed 18305455
International Warfarin Pharmacogenetics Consortium; Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, Lee MT, Limdi NA, Page D, Roden DM, Wagner MJ, Caldwell MD, Johnson JA. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009 Feb 19;360(8):753-64. doi: 10.1056/NEJMoa0809329.
PubMed 19228618
Hamberg AK, Hellman J, Dahlberg J, Jonsson EN, Wadelius M. A Bayesian decision support tool for efficient dose individualization of warfarin in adults and children. BMC Med Inform Decis Mak. 2015 Feb 7;15:7. doi: 10.1186/s12911-014-0128-0.
PubMed 25889768
Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, Kesteven P, Christersson C, Wahlstrom B, Stafberg C, Zhang JE, Leathart JB, Kohnke H, Maitland-van der Zee AH, Williamson PR, Daly AK, Avery P, Kamali F, Wadelius M; EU-PACT Group. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013 Dec 12;369(24):2294-303. doi: 10.1056/NEJMoa1311386. Epub 2013 Nov 19.
PubMed 24251363
Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, Rosenberg YD, Eby CS, Madigan RA, McBane RB, Abdel-Rahman SZ, Stevens SM, Yale S, Mohler ER 3rd, Fang MC, Shah V, Horenstein RB, Limdi NA, Muldowney JA 3rd, Gujral J, Delafontaine P, Desnick RJ, Ortel TL, Billett HH, Pendleton RC, Geller NL, Halperin JL, Goldhaber SZ, Caldwell MD, Califf RM, Ellenberg JH; COAG Investigators. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013 Dec 12;369(24):2283-93. doi: 10.1056/NEJMoa1310669. Epub 2013 Nov 19.
PubMed 24251361
Li X, Yang J, Wang X, Xu Q, Zhang Y, Yin T. Clinical benefits of pharmacogenetic algorithm-based warfarin dosing: meta-analysis of randomized controlled trials. Thromb Res. 2015 Apr;135(4):621-9. doi: 10.1016/j.thromres.2015.01.018. Epub 2015 Jan 17.
PubMed 25628141

Want to know more?

Each site lists its own contact. Pick the site nearest to you.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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REVIVE-FR Registry
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Active, not recruitingObservational study
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All Heart Valve Prosthesis trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Individualized Administration of Warfarin by Polymorphisms of VKORC1 and CYP2C9 Genes:A Randomized Controlled Trial, Multi-center Trial
ClinicalTrials.gov ID: NCT03797534
Acronym / sponsor ID: CLW2018WA
Conditions: Heart Valve Prosthesis
Keywords: warfarin, gene
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 600 participants (estimated)
Lead sponsor: Fujian Medical UniversityUniversity, hospital or other
Study start: 1 Feb 2019 (estimated)
Primary completion: 1 Jan 2022 (estimated)
Study completion: 1 Jan 2023 (estimated)
First posted: 9 Jan 2019 (actual)
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 explore the individualized administration model of warfarin suitable for Chinese people, and provide a scientific reference for the use of warfarin to Chinese people.

Detailed description

clinicians to judge the standard of the selection criteria;
to obtain the consent of the patient and sign an informed consent certificate;
to collect 2ml anticoagulant blood before the drug, fill in the application form for individualized drug use in warfarin, and indicate the experimental group and control group;
the specimen assigned to the laboratory for Genotyping;
lab to calculate the predicted stable warfarin dose and the results fed back to the clinician within one working day after receiving the specimen;
in the control group, the drug retained at the regular dose, and the first 3 days of the experimental group administered at the predicted dose;
the dosage of warfarin in the two groups of cases adjusted to the stable dose according to the value, and the adjustment amplitude of the experimental group also referred to the predicted stable dose.
to monitor INR once a day during hospitalization, and to those who do not receive a stable dose of discharge, follow up and monitor INR once a week until a stable dose or medication is obtained for 90 days;
to document clinical trial records, including the daily use of warfarin, each detection of the appearance of the situation like INR value, bleeding, venous embolism and other side effects.

Finally，according to the outcome parameters,statistical analysis were performed with SPSS 11.5 software. A value of P < 0.05 was considered statistically significant.

Study design

Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, care provider)
Number of arms: 2

Arm	Type	Receives
Standard anticoagulant group	No intervention	–
Bayesian model group	Experimental	Other: dose regime

Who may qualify

Ages: 14 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (4 listed)

Age > 14 years old；
Warfarin anticoagulant therapy is required for at least 3 months；
The genotype of patient VKORC1 is non-AA, CYP2C9 genotype is non*1/*1； the patients who are followed up, regularly monitored for INR and willing to provide peripheral blood for DNA extraction and genetic testing；
The patient or family members can understand the research plan and will participate in this study and provide a written informed consent；

Key exclusion criteria (17 listed)

Severe liver dysfunction (ChildPugh ≥ 10);
Severe infection, respiratory failure;
Severe heart failure ( NYHA ≥ IV);
Severe renal insufficiency (Ccr ≤ 20ml / min);
Cancer;

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
dose regimeThe initial dose of the experimental group will be calculated by the Bayesian model.	Other	Bayesian model group

Primary outcome

excessive anticoagulant time ratio
Time frame: 3 months postoperatively
INR>3，INR>4
The occurrence of primary bleeding events
Time frame: 3 months postoperatively
gastrointestinal hemorrhage, intracerebral hemorrhage,etc
The occurance of secondary bleeding events
Time frame: 3 months postoperatively
nasal bleeding, skin stasis,etc
The occurrence of thrombosis events
Time frame: 3 months postoperatively
ischemic stroke, deep vein thrombosis,etc

8 secondary outcomes

Percentage of time in therapeutic range
Time frame: 3 months, 6 months, 12 months postoperatively
The time required to reach the treatment target INR for the first time;
Time frame: 3 months postoperatively
The time required from the beginning of treatment to the stable dose;
Time frame: 3 months postoperatively
The percentage of time below the target INR range;
Time frame: 3 months postoperatively
The percentage of time above the target INR range;
Time frame: 3 months postoperatively
The number of dose adjustments and the number of INR measured during the first month of treatment;
Time frame: 3 months postoperatively
The proportion of patients in each group receiving a stable dose after follow-up;
Time frame: 3 months postoperatively
The proportion of patients in each group having side effects after follow-up
Time frame: 3 months postoperatively

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2019.
Background: PubMed 18305455Gage BF, Eby C, Johnson JA, Deych E, Rieder MJ, Ridker PM, Milligan PE, Grice G, Lenzini P, Rettie AE, Aquilante CL, Grosso L, Marsh S, Langaee T, Farnett LE, Voora D, Veenstra DL, Glynn RJ, Barrett A, McLeod HL. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther. 2008 Sep;84(3):326-31. doi: 10.1038/clpt.2008.10. Epub 2008 Feb 27.
Background: PubMed 19228618International Warfarin Pharmacogenetics Consortium; Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, Lee MT, Limdi NA, Page D, Roden DM, Wagner MJ, Caldwell MD, Johnson JA. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009 Feb 19;360(8):753-64. doi: 10.1056/NEJMoa0809329.
Background: PubMed 25889768Hamberg AK, Hellman J, Dahlberg J, Jonsson EN, Wadelius M. A Bayesian decision support tool for efficient dose individualization of warfarin in adults and children. BMC Med Inform Decis Mak. 2015 Feb 7;15:7. doi: 10.1186/s12911-014-0128-0.
Background: PubMed 24251363Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, Kesteven P, Christersson C, Wahlstrom B, Stafberg C, Zhang JE, Leathart JB, Kohnke H, Maitland-van der Zee AH, Williamson PR, Daly AK, Avery P, Kamali F, Wadelius M; EU-PACT Group. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013 Dec 12;369(24):2294-303. doi: 10.1056/NEJMoa1311386. Epub 2013 Nov 19.
Background: PubMed 24251361Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, Rosenberg YD, Eby CS, Madigan RA, McBane RB, Abdel-Rahman SZ, Stevens SM, Yale S, Mohler ER 3rd, Fang MC, Shah V, Horenstein RB, Limdi NA, Muldowney JA 3rd, Gujral J, Delafontaine P, Desnick RJ, Ortel TL, Billett HH, Pendleton RC, Geller NL, Halperin JL, Goldhaber SZ, Caldwell MD, Califf RM, Ellenberg JH; COAG Investigators. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013 Dec 12;369(24):2283-93. doi: 10.1056/NEJMoa1310669. Epub 2013 Nov 19.
Background: PubMed 25628141Li X, Yang J, Wang X, Xu Q, Zhang Y, Yin T. Clinical benefits of pharmacogenetic algorithm-based warfarin dosing: meta-analysis of randomized controlled trials. Thromb Res. 2015 Apr;135(4):621-9. doi: 10.1016/j.thromres.2015.01.018. Epub 2015 Jan 17.

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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.

the Department of Cardiovascular Surgery

Fuzhou, China

86 13358255333

343983217@qq.com

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing dose regime in people with Heart Valve Prosthesis, run by Fujian Medical University 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 17 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 15 Jan 2019. 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.

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?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

excessive anticoagulant time ratio (time frame: 3 months postoperatively). The study lists 4 primary outcomes in all. 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 NCT03797534, which also lists 6 linked publications.

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 15 Jan 2019.