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Atrial FibrillationNCT02211326

Genotype-guided Warfarin Individualized Treatment

A study testing Genotype-guided dosing algorithm for warfarin and Standard initiation dose for warfarin in people with Atrial Fibrillation and Deep Venous Thrombosis, run by The Third Xiangya Hospital of Central South University at 15 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine whether the international pharmacogenetic algorithm is better than the standard initiation dosing and whether the two algorithms are suitable for Chinese elderly patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Atrial Fibrillation, Deep Venous Thrombosis
What is being tested?
Genotype-guided dosing algorithm for warfarin and Standard initiation dose for warfarin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
660 participants
Where
15 sitesChina
Study dates
1 Sep 2014to 1 May 2017
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Inclusion criteria：1) Chinese male or female aged ≥18 years; 2) Requiring at least 12-week warfarin therapy as judged by clinicians; 3) Subjects with DVT/AF and a post-therapy target INR of 1.5-2.5; 4) Capable of providing written informed consent; 5) Capable of maintaining excellent communications with investigators and completing trial in accordance with trial stipulations.

Exclusion criteria：1) Subjects previously taking warfarin; 2) Known genotypes of CYP2C9 or/and VKORC1; 3) Subjects receiving or expecting to receive other therapies or other anticoagulants; 4) Subjects with contraindications for warfarin; 5) Subjects with severe cognitive dysfunctions; 6) Baseline INR ≥1.5; 7) Subjects with drug or alcohol dependence within the last 12 months; 8) Subjects receiving blood transfusion or bone marrow transplantation within the last 2 weeks; 9) Planning to receive invasive examinations (except for standard endoscopy) with a hemorrhagic tendency or undergoing surgery during trial.10) Prior to randomization, subjects receiving any trial drug or device within the last 3 months or planning to receive such an investigational therapy during trial; 11) Subjects with the following diagnoses or conditions: active malignant carcinomas (diagnosed within the last 5 years), but excluding adequately-treated non-melanoma skin cancer or other non-invasive or in situ cancer (e.g. cervical cancer in situ); anti-neoplastic therapy within the last 5 years (medication, radiotherapy or/and surgery); overt active disease or infection; life expectancy <6 months; 12）Other clinical reasons for unsuitable recruitment as judged by clinicians.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

China15 sites

  • The People's Hospital of Hunan Province

    Changsha, Hunan, 410002

  • The Central Hospital of Changsha

    Changsha, Hunan, 410004

  • The Fourth Hospital of Changsha

    Changsha, Hunan, 410006

  • The Third Xiangya Hospital of Central South University

    Changsha, Hunan, 410013

  • The Third Hospital of Changsha

    Changsha, Hunan

  • The Xiangya Hospital of Central South University

    Changsha, Hunan

  • The First People's Hospital of Chenzhou

    Chenzhou, Hunan, 423000

  • The First Affiliated Hospital of Nanhua university

    Hengyang, Hunan

  • The Second Affiliated Hospital of Nanhua university

    Hengyang, Hunan

  • The Central Hospital of Loudi

    Loudi, Hunan, 417000

  • The Central Hospital of Shaoyang

    Shaoyang, Hunan, 422000

  • The First People's Hospital of Shaoyang

    Shaoyang, Hunan, 422001

  • The Central Hospital of Xiangtan

    Xiangtan, Hunan, 411100

  • The First People's Hospital of Xiangtan

    Xiangtan, Hunan, 411101

  • The Central Hospital of Yiyang

    Yiyang, Hunan, 413000

Other trials in China

About this study

Official title: Pharmacogenetic Algorithm of Response to Warfarin During Initial Anticoagulation in Chinese Elderly Patients

The purpose of this study is to determine whether the international pharmacogenetic algorithm is better than the standard initiation dosing and whether the two algorithms are suitable for Chinese elderly patients.

Read the detailed description

The study protocol is a multicenter, randomized, patient-blinded and controlled trial, comparing two approaches among 864 enrolled AF(atrial fibrillation) or DVT(deep venous thrombosis) patients for guiding warfarin initial anticoagulation in Chinese elderly patients: the intervention group using the algorithm of International Warfarin Pharmacogenetic Consortium and its dose revision, and the control group using a standard initiation dose (2.25 mg).The study hypothesis is that the intervention group relative to the control group will increase the percentage of time in therapeutic INR (international normalized ratio) range during the first 3 months.This trial is the first prospective large-scale randomized controlled trial for elders in China. It is of great significance for promoting special crowd individualization of anticoagulants at home and abroad.

Being tested
Genotype-guided dosing algorithm for warfarin, Standard initiation dose for warfarin
Keywords
AF or DVT, Age Over 18 Years, Acquired
Medical subject headings
Atrial Fibrillation, Venous Thrombosis

What participants receive

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

  • Genotype-guided dosing algorithm for warfarinBehavioural

    Intervention：initial dosing of warfarin for the first 3 days of treatment will be determined by IWPC( International Warfarin Pharmacogenetics Consortium) algorithm (PG-1),a second dose adjustment will be made after 3 doses of warfarin using a dose revision algorithm (PG-2) that combined INR values,the dose will be adjusted depending on the measurements of INR values after 7 days.The overall follow-up period is 12 weeks.

  • Standard initiation dose for warfarinBehavioural

    Intervention：initial dosing of warfarin for the first 3 days of treatment will be determined by standard initiation dose. Following this initiation dose of warfarin,the dose will be adjusted depending on the measurements of INR values after 3 days.The overall follow-up period is 12 weeks.

Study groups in NCT02211326
Study groupRoleWhat they receive
genotype-guided groupExperimentalInterventions：on day1~day3, patients received dose according to IWPC formula (PGx-1) included clinical variables and genotype data for VKORC1, CYP2C9*1, CYP2C9*2, and CYP2C9*3; on day4~day7, patients received dose according to Lenzini formula consisted of clinical variables, VKORC1, CYP2C9*2, CYP2C9*3 and previous INR and dosing information (PGx-2); and on day8, the clinicians adjusted the dose according to observed INR.The overall follow-up period is 12 weeks.
Receives: Behavioral: Genotype-guided dosing algorithm for warfarin
control groupActive comparatorInterventions：on day1~day3, patients were given initial dose (2.25mg); and starting from day4, the clinicians began to adjust the dose for patients according to observed INR.The overall follow-up period is 12 weeks.
Receives: Behavioral: Standard initiation dose for warfarin

What is being measured

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

  1. %TTR

    percentage of time in the therapeutic INR (%TTR) of INR 2-3 (<60 years old) or 1.5-2.5 (≥ 60 years old) within 12 weeks

    Measured: 12 weeks

Secondary outcomes (3)

  1. the time to reach therapeutic INR

    the time to reach therapeutic INR

    Measured: 12 weeks

  2. the time to reach stable warfarin dose which defined as the dose to achieve INR within ±0.1 of therapeutic range at Day 8 post-dose

    the time to reach stable warfarin dose which defined as the dose to achieve INR within ±0.1 of therapeutic range at Day 8 post-dose

    Measured: 12 weeks

  3. The number of adjustment units in the dose of warfarin (with 0.375 mg (1/8 tablet) as a unit); Incidence of INR ≥ 4

    The number of adjustment units in the dose of warfarin (with 0.375 mg (1/8 tablet) as a unit); Incidence of INR ≥ 4

    Measured: 12 weeks

Timeline

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

  1. First posted7 Aug 2014 (estimated)
  2. Study start1 Sep 2014
  3. Primary completion16 Jan 2017
  4. Study completion1 May 2017

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
660 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02211326
Sponsor's protocol ID
XY3-WARF1405A01
Other IDs
ChiCTR-TRC-14004757
Status last verified
Nov 2017
First submitted
6 Aug 2014
Last updated
6 Nov 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, Blatchford J, Devenny K, Friedman J, Guiver K, Harper R, Khder Y, Lobmeyer MT, Maas H, Voigt JU, Simoons ML, Van de Werf F; RE-ALIGN Investigators. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013 Sep 26;369(13):1206-14. doi: 10.1056/NEJMoa1300615. Epub 2013 Aug 31.

    PubMed 23991661

  • Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365(10):883-91. doi: 10.1056/NEJMoa1009638. Epub 2011 Aug 10.

    PubMed 21830957

  • Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Spinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013 Nov 28;369(22):2093-104. doi: 10.1056/NEJMoa1310907. Epub 2013 Nov 19.

    PubMed 24251359

  • Arepally GM, Ortel TL. Changing practice of anticoagulation: will target-specific anticoagulants replace warfarin? Annu Rev Med. 2015;66:241-53. doi: 10.1146/annurev-med-051113-024633.

    PubMed 25587651

  • Healey JS, Oldgren J, Ezekowitz M, Zhu J, Pais P, Wang J, Commerford P, Jansky P, Avezum A, Sigamani A, Damasceno A, Reilly P, Grinvalds A, Nakamya J, Aje A, Almahmeed W, Moriarty A, Wallentin L, Yusuf S, Connolly SJ; RE-LY Atrial Fibrillation Registry and Cohort Study Investigators. Occurrence of death and stroke in patients in 47 countries 1 year after presenting with atrial fibrillation: a cohort study. Lancet. 2016 Sep 17;388(10050):1161-9. doi: 10.1016/S0140-6736(16)30968-0. Epub 2016 Aug 8.

    PubMed 27515684

  • Kuang Y, Liu Y, Pei Q, Ning X, Zou Y, Liu L, Song L, Guo C, Sun Y, Deng K, Zou C, Cao D, Cui Y, Wu C, Yang G. Long Short-Term Memory Network for Development and Simulation of Warfarin Dosing Model Based on Time Series Anticoagulant Data. Front Cardiovasc Med. 2022 May 11;9:881111. doi: 10.3389/fcvm.2022.881111. eCollection 2022.

    PubMed 35647078

  • Ning X, Kuang Y, Yang G, Xie J, Miao D, Guo C, Huang Z. Influence of renal insufficiency on anticoagulant effects and safety of warfarin in Chinese patients: analysis from a randomized controlled trial. Naunyn Schmiedebergs Arch Pharmacol. 2021 Jun;394(6):1275-1283. doi: 10.1007/s00210-020-02037-3. Epub 2021 Jan 6.

    PubMed 33404689

  • Guo C, Kuang Y, Zhou H, Yuan H, Pei Q, Li J, Jiang W, Ng CM, Chen X, Huo Y, Cui Y, Wang X, Yu J, Sun X, Yu W, Chen P, Miao D, Liu W, Yu Z, Ouyang Z, Shi X, Lv C, Peng Z, Xiong G, Zeng G, Zeng J, Dai H, Peng J, Zhang Y, Xu F, Wu J, Chen X, Gong H, Yang Z, Wu X, Fang Q, Yang L, Li H, Tan H, Huang Z, Tang X, Yang Q, Tu S, Wang X, Xiang Y, Huang J, Wang X, Cai J, Jiang S, Huang L, Peng J, Gong L, Zou C, Yang G. Genotype-Guided Dosing of Warfarin in Chinese Adults: A Multicenter Randomized Clinical Trial. Circ Genom Precis Med. 2020 Aug;13(4):e002602. doi: 10.1161/CIRCGEN.119.002602. Epub 2020 Jun 8.

    PubMed 32510984

Questions about this trial

What is this clinical trial studying?

A study testing Genotype-guided dosing algorithm for warfarin and Standard initiation dose for warfarin in people with Atrial Fibrillation and Deep Venous Thrombosis, run by The Third Xiangya Hospital of Central South University at 15 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites 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?

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?

%TTR (time frame: 12 weeks). 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 NCT02211326, which also lists 8 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 6 Nov 2017.

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