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Individualized Administration of Warfarin by Polymorphisms of VKORC1 and CYP2C9 Genes

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ClinicalTrials.gov Identifier: NCT03797534
Recruitment Status : Recruiting
First Posted : January 9, 2019
Last Update Posted : January 15, 2019
Sponsor:
Information provided by (Responsible Party):
Liang-Wan Chen MD, Fujian Medical University

Brief 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.

Condition or disease Intervention/treatment Phase
Heart Valve Prosthesis Other: dose regime Not Applicable

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:

  1. clinicians to judge the standard of the selection criteria;
  2. to obtain the consent of the patient and sign an informed consent certificate;
  3. 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;
  4. the specimen assigned to the laboratory for Genotyping;
  5. lab to calculate the predicted stable warfarin dose and the results fed back to the clinician within one working day after receiving the specimen;
  6. 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;
  7. 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.
  8. 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;
  9. 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Supportive Care
Official Title: Individualized Administration of Warfarin by Polymorphisms of VKORC1 and CYP2C9 Genes:A Randomized Controlled Trial, Multi-center Trial
Estimated Study Start Date : February 1, 2019
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : January 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: Standard anticoagulant group
Experimental: Bayesian model group Other: dose regime
The initial dose of the experimental group will be calculated by the Bayesian model.




Primary Outcome Measures :
  1. excessive anticoagulant time ratio [ Time Frame: 3 months postoperatively ]
    INR>3,INR>4

  2. The occurrence of primary bleeding events [ Time Frame: 3 months postoperatively ]
    gastrointestinal hemorrhage, intracerebral hemorrhage,etc

  3. The occurance of secondary bleeding events [ Time Frame: 3 months postoperatively ]
    nasal bleeding, skin stasis,etc

  4. The occurrence of thrombosis events [ Time Frame: 3 months postoperatively ]
    ischemic stroke, deep vein thrombosis,etc


Secondary Outcome Measures :
  1. Percentage of time in therapeutic range [ Time Frame: 3 months, 6 months, 12 months postoperatively ]
  2. The time required to reach the treatment target INR for the first time; [ Time Frame: 3 months postoperatively ]
  3. The time required from the beginning of treatment to the stable dose; [ Time Frame: 3 months postoperatively ]
  4. The percentage of time below the target INR range; [ Time Frame: 3 months postoperatively ]
  5. The percentage of time above the target INR range; [ Time Frame: 3 months postoperatively ]
  6. The number of dose adjustments and the number of INR measured during the first month of treatment; [ Time Frame: 3 months postoperatively ]
  7. The proportion of patients in each group receiving a stable dose after follow-up; [ Time Frame: 3 months postoperatively ]
  8. The proportion of patients in each group having side effects after follow-up [ Time Frame: 3 months postoperatively ]


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Ages Eligible for Study:   14 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age > 14 years old;
  2. Warfarin anticoagulant therapy is required for at least 3 months;
  3. 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;
  4. The patient or family members can understand the research plan and will participate in this study and provide a written informed consent;

Exclusion Criteria:

  1. Severe liver dysfunction (ChildPugh ≥ 10);
  2. Severe infection, respiratory failure;
  3. Severe heart failure ( NYHA ≥ IV);
  4. Severe renal insufficiency (Ccr ≤ 20ml / min);
  5. Cancer;
  6. Diseases of the blood system;
  7. Severe pulmonary hypertension (PAPm ≥ 45mmHg);
  8. Abnormal thyroid function;
  9. Patients with a history of venous thromboembolism, or serious events such as severe bleeding or embolism;
  10. Women who are pregnant or breastfeeding;
  11. Taking or planning to take other oral anticoagulants;
  12. The base INR value is >1.4;
  13. VKORC1, CYP2C9 genotypes are AA, *1/*1;
  14. Secondary valve replacement surgery;
  15. Emergency hospital admission for valve surgery;
  16. Diagnosis of coronary atherosclerotic heart disease;
  17. Severe mental illness, mental disorder ; -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03797534


Locations
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China, Fujian
the Department of Cardiovascular Surgery Recruiting
FuZhou, Fujian, China, 350001
Contact: Liang-Wan Chen, M.D Ph.D    86 13358255333    343983217@qq.com   
Contact: Jin-Hua Zhang, Ph.D    86 13609532263    pollyzhang2006@126.com   
Sponsors and Collaborators
Fujian Medical University

Publications:

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Responsible Party: Liang-Wan Chen MD, The director of the department of cardiovascular surgery, Fujian Medical University
ClinicalTrials.gov Identifier: NCT03797534     History of Changes
Other Study ID Numbers: CLW2018WA
First Posted: January 9, 2019    Key Record Dates
Last Update Posted: January 15, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Liang-Wan Chen MD, Fujian Medical University:
warfarin
gene
Additional relevant MeSH terms:
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Warfarin
Anticoagulants