低治疗范围内时间患者基于药物遗传学的华法林给药算法评估——一项随机对照试验的研究方案
Evaluation of a pharmacogenetic-based warfarin dosing algorithm in patients with low time in therapeutic range - study protocol for a randomized controlled trial.
作者信息
Marcatto Leiliane Rodrigues, Sacilotto Luciana, Bueno Carolina Tosin, Facin Mirella, Strunz Celia Maria Cassaro, Darrieux Francisco Carlos Costa, Scanavacca Maurício Ibrahim, Krieger Jose Eduardo, Pereira Alexandre Costa, Santos Paulo Caleb Junior Lima
机构信息
Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, São Paulo, SP, CEP 05403-000, Brazil.
Arrhythmia Unit, Heart Institute (InCor), University of São Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, São Paulo, SP, CEP 05403-000, Brazil.
出版信息
BMC Cardiovasc Disord. 2016 Nov 17;16(1):224. doi: 10.1186/s12872-016-0405-1.
BACKGROUND
Time in therapeutic range (TTR) is a measurement of quality of warfarin therapy and lower TTR values (<50%) are associated with greater risk of thromboembolic and bleeding events. Recently, we developed a pharmacogenetic-based warfarin dosing algorithm specifically calibrated for a Brazilian patient sample. The aims of this study are: to evaluate the impact of a genetic-based algorithm, compared to traditional anticoagulation, in the time to achieve the therapeutic target and in TTR percentage; and to assess the cost-effectiveness of genotype-guided warfarin dosing in a specific cohort of patients with low TTR (<50%) from a tertiary cardiovascular hospital.
METHODS/DESIGN: This study is a randomized controlled trial in patients (n = 300) with atrial fibrillation with TTR < 50%, based on the last three INR values. At the first consultation, patients will be randomized into two groups: TA group (traditional anticoagulation) and PA group (pharmacogenetic anticoagulation). For the first group, the physician will adjust the dose according to current INR value and, for the second group, a pharmacogenetic algorithm will be used. At the second, third, fourth and fifth consultations (with an interval of 7 days each) INR will be measured and, if necessary, the dose will be adjusted based on guidelines. Afterwards, patients who are INR stable will begin measuring their INR in 30 day intervals; if the patient's INR is not stable, the patient will return in 7 days for a new measurement of the INR. Outcomes measures will include the time to achieve the therapeutic target and the percentage of TTR at 4 and 12 weeks. In addition, as a secondary end-point, pharmacoeconomic analysis will be carried out. Ethical approval was granted by the Ethics Committee for Medical Research on Human Beings of the Clinical Hospital of the University of São Paulo Medical School.
DISCUSSION
This randomized study will include patients with low TTR and it will evaluate whether a population-specific genetic algorithm might be more effective than traditional anticoagulation for a selected group of poorly anticoagulated patients.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT02592980 . Registered on 29 October 2015.
背景
治疗范围内时间（TTR）是华法林治疗质量的一项衡量指标，较低的TTR值（<50%）与血栓栓塞和出血事件的更高风险相关。最近，我们开发了一种基于药物遗传学的华法林给药算法，该算法是专门针对巴西患者样本进行校准的。本研究的目的是：评估与传统抗凝治疗相比，基于基因的算法对达到治疗目标的时间和TTR百分比的影响；并评估在一家三级心血管医院中，基因型指导的华法林给药在特定TTR较低（<50%）患者队列中的成本效益。
方法/设计：本研究是一项针对TTR<50%的房颤患者（n = 300）的随机对照试验，基于最近三次国际标准化比值（INR）值。在首次就诊时，患者将被随机分为两组：TA组（传统抗凝治疗）和PA组（药物遗传学抗凝治疗）。对于第一组，医生将根据当前INR值调整剂量，对于第二组，将使用药物遗传学算法。在第二次、第三次、第四次和第五次就诊时（每次间隔7天）测量INR，如有必要，将根据指南调整剂量。之后，INR稳定的患者将开始每30天测量一次INR；如果患者的INR不稳定，患者将在7天后返回进行新的INR测量。结局指标将包括达到治疗目标的时间以及4周和12周时的TTR百分比。此外，作为次要终点，将进行药物经济学分析。圣保罗大学医学院临床医院人类医学研究伦理委员会已批准本研究。
讨论
这项随机研究将纳入TTR较低的患者，并将评估针对一组抗凝效果不佳的选定患者，特定人群的基因算法是否可能比传统抗凝治疗更有效。
试验注册
ClinicalTrials.gov，NCT02592980。于2015年10月29日注册。
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