Genotype-guided Warfarin Individualized Treatment

NCT02211326 | Completed DMC

• 2 other identifiers: XY3-WARF1405A01ChiCTR-TRC-14004757
• Study Type: interventional
• Target: 660
• Locations: 1 country
• Sites: 15

Brief 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.

Conditions

Atrial Fibrillation; Deep Venous Thrombosis

Keywords

AF or DVT; Age Over 18 Years, Acquired

Outcome Measures

Primary Outcomes (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

  12 weeks

Secondary Outcomes (3)

• the time to reach therapeutic INR

  12 weeks

• 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

  12 weeks

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

  12 weeks

Other Outcomes (1)

• the number of additional clinic visits

  12 weeks

Study Arms (2)

genotype-guided group

EXPERIMENTAL

Interventions：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.

Behavioral: Genotype-guided dosing algorithm for warfarin

control group

ACTIVE COMPARATOR

Interventions：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.

Behavioral: Standard initiation dose for warfarin

Interventions

Genotype-guided dosing algorithm for warfarin BEHAVIORAL

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.

genotype-guided group

Standard initiation dose for warfarin BEHAVIORAL

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.

control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• The Third Xiangya Hospital of Central South University: lead

Study Sites (15)

The People's Hospital of Hunan Province

Changsha, Hunan, 410002, China

Location

The Central Hospital of Changsha

Changsha, Hunan, 410004, China

Location

The Fourth Hospital of Changsha

Changsha, Hunan, 410006, China

Location

The Third Xiangya Hospital of Central South University

Changsha, Hunan, 410013, China

Location

The Third Hospital of Changsha

Changsha, Hunan, China

Location

The Xiangya Hospital of Central South University

Changsha, Hunan, China

Location

The First People's Hospital of Chenzhou

Chenzhou, Hunan, 423000, China

Location

The First Affiliated Hospital of Nanhua university

Hengyang, Hunan, China

Location

The Second Affiliated Hospital of Nanhua university

Hengyang, Hunan, China

Location

The Central Hospital of Loudi

Loudi, Hunan, 417000, China

Location

The Central Hospital of Shaoyang

Shaoyang, Hunan, 422000, China

Location

The First People's Hospital of Shaoyang

Shaoyang, Hunan, 422001, China

Location

The Central Hospital of Xiangtan

Xiangtan, Hunan, 411100, China

Location

The First People's Hospital of Xiangtan

Xiangtan, Hunan, 411101, China

Location

The Central Hospital of Yiyang

Yiyang, Hunan, 413000, China

Location

Related Publications (8)

• 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.

  PMID: 23991661 BACKGROUND

• 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.

  PMID: 21830957 BACKGROUND

• 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.

  PMID: 24251359 BACKGROUND

• 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.

  PMID: 25587651 BACKGROUND

• 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.

  PMID: 27515684 BACKGROUND

• 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.

  PMID: 35647078 DERIVED

• 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.

  PMID: 33404689 DERIVED

• 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.

  PMID: 32510984 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation; Venous Thrombosis

Interventions

Warfarin

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thrombosis; Embolism and Thrombosis; Vascular Diseases

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• GuoPing Yang, professor

  The Third Xiangya Hospital of Central South University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2014
• First Posted: August 7, 2014
• Study Start: September 1, 2014
• Primary Completion: January 16, 2017
• Study Completion: May 1, 2017
• Last Updated: November 6, 2017

Record last verified: 2017-11

Locations

CN (15)