Genotype-guided Warfarin Individualized Treatment
2017년 11월 1일 업데이트: The Third Xiangya Hospital of Central South University
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.
연구 개요
상태
완전한
상세 설명
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.
연구 유형
중재적
등록 (실제)
660
단계
- 해당 없음
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Hunan
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Changsha, Hunan, 중국, 410013
- The Third XIANGYA Hospital of Central South University
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Changsha, Hunan, 중국, 410002
- The People's Hospital of Hunan Province
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Changsha, Hunan, 중국, 410004
- the central hospital of Changsha
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Changsha, Hunan, 중국, 410006
- The Fourth Hospital of Changsha
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Changsha, Hunan, 중국
- The Third Hospital of Changsha
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Changsha, Hunan, 중국
- The Xiangya Hospital of Central South University
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Chenzhou, Hunan, 중국, 423000
- The First People's Hospital of Chenzhou
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Hengyang, Hunan, 중국
- The First Affiliated Hospital of Nanhua University
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Hengyang, Hunan, 중국
- The Second Affiliated Hospital of Nanhua University
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Loudi, Hunan, 중국, 417000
- The Central Hospital of Loudi
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Shaoyang, Hunan, 중국, 422000
- The Central Hospital of Shaoyang
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Shaoyang, Hunan, 중국, 422001
- The First People's Hospital of Shaoyang
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Xiangtan, Hunan, 중국, 411100
- The Central Hospital of Xiangtan
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Xiangtan, Hunan, 중국, 411101
- The First People's Hospital of Xiangtan
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Yiyang, Hunan, 중국, 413000
- The Central Hospital of Yiyang
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
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.
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 하나의
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: genotype-guided group
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.
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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.
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활성 비교기: control group
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.
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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.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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%TTR
기간: 12 weeks
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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
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12 weeks
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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the time to reach therapeutic INR
기간: 12 weeks
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the time to reach therapeutic INR
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12 weeks
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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
기간: 12 weeks
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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
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12 weeks
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The number of adjustment units in the dose of warfarin (with 0.375 mg (1/8 tablet) as a unit); Incidence of INR ≥ 4
기간: 12 weeks
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The number of adjustment units in the dose of warfarin (with 0.375 mg (1/8 tablet) as a unit); Incidence of INR ≥ 4
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12 weeks
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기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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the number of additional clinic visits
기간: 12 weeks
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the number of additional clinic visits
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12 weeks
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 수석 연구원: GuoPing Yang, professor, The Third XIANGYA Hospital of Central South University
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2014년 9월 1일
기본 완료 (실제)
2017년 1월 16일
연구 완료 (실제)
2017년 5월 1일
연구 등록 날짜
최초 제출
2014년 8월 6일
QC 기준을 충족하는 최초 제출
2014년 8월 6일
처음 게시됨 (추정)
2014년 8월 7일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2017년 11월 6일
QC 기준을 충족하는 마지막 업데이트 제출
2017년 11월 1일
마지막으로 확인됨
2017년 11월 1일
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .