Genotype-guided Warfarin Individualized Treatment

Atrial Fibrillation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02211326
• Other study ID #: XY3-WARF1405A01
• Secondary ID: ChiCTR-TRC-14004
• Status: Completed
• Phase: N/A
• First received: August 6, 2014
• Last updated: November 1, 2017
• Start date: September 1, 2014
• Est. completion date: May 1, 2017

Study information

• Verified date: November 2017
• Source: The Third Xiangya Hospital of Central South University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 660
• Est. completion date: May 1, 2017
• Est. primary completion date: January 16, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atrial Fibrillation
• Deep Venous Thrombosis
• Thrombosis
• Venous Thrombosis

Intervention

Behavioral:
• Genotype-guided dosing algorithm for warfarin
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 warfarin
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.

Locations

Country	Name	City	State
China	The Central Hospital of Changsha	Changsha	Hunan
China	The Fourth Hospital of Changsha	Changsha	Hunan
China	The People's Hospital of Hunan Province	Changsha	Hunan
China	The Third Hospital of Changsha	Changsha	Hunan
China	The Third Xiangya Hospital of Central South University	Changsha	Hunan
China	The Xiangya Hospital of Central South University	Changsha	Hunan
China	The First People's Hospital of Chenzhou	Chenzhou	Hunan
China	The First Affiliated Hospital of Nanhua university	Hengyang	Hunan
China	The Second Affiliated Hospital of Nanhua university	Hengyang	Hunan
China	The Central Hospital of Loudi	Loudi	Hunan
China	The Central Hospital of Shaoyang	Shaoyang	Hunan
China	The First People's Hospital of Shaoyang	Shaoyang	Hunan
China	The Central Hospital of Xiangtan	Xiangtan	Hunan
China	The First People's Hospital of Xiangtan	Xiangtan	Hunan
China	The Central Hospital of Yiyang	Yiyang	Hunan

Sponsors (1)

Lead Sponsor	Collaborator
The Third Xiangya Hospital of Central South University

Country where clinical trial is conducted

China, 

References & Publications (5)

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. Review. — View Citation

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. — View Citation

Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar 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. — View Citation

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. Erratum in: Lancet. 2017 Feb 11;389(10069):602. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	the number of additional clinic visits	the number of additional clinic visits	12 weeks
Primary	%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	the time to reach therapeutic INR	the time to reach therapeutic INR	12 weeks
Secondary	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	12 weeks
Secondary	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	12 weeks