Direct Oral Anticoagulants Pharmacodynamics in Octogenarian Patients With Atrial Fibrillation
试验速览
- 阶段
- 不适用
- 入组人数
- 150
- 试验地点
- 2
- 主要终点
- Diluted thrombin time (DTT) for Dabigatran
研究概览
简要总结
Background: The incidence of atrial fibrillation(AF) increases substantially with age and it is estimated that more than one third of AF patients are octogenarians. Direct oral anticoagulants (DOACs) were found favorable compared to warfarin with respect to efficacy and safety ( bleeding) across wide range of ages.
Nevertheless, the rates of bleeding among elderly patients were shown to increase substantially with all anticoagulants. Dose-adjustments of DOAC are not universally performed among patients older than 80 years old and currently there is paucity of data regarding the actual drugs level among these patients. Accordingly, the investigators sought to investigate the drug levels of the different DOACs among "real world" octogenarians who receiving guideline-recommended dosage.
Methods: A cross sectional, prospective study of 120 hospitalized and ambulatory patients who are treated with DOACs for AF.
DOACs blood levels with be compared between octogenarians (n=70) and younger patient group ( age≤70 year-old; n=50).The cohort will include: 1)Sixty patients on APIXABAN: 40 octogenarians and 20 younger than 70 years, 2)Forty patients on RIVAROXABAN: 20 octogenarians and 20 younger than 70 years, and 3) Twenty patients treated with DABIGATRAN: 10 octogenarians and 10 younger than 70 years.
DOACs Pharmacodynamic analysis will be performed using commercial kits for diluted thrombin time(DTT) and anti-factor Xa activity (AFXa). Drug level will be measured at steady state( through levels) and at Tmax after at least 4 days of complete adherence for DOAC consumption.
Study End-Points:The study main objectives are: 1) DOACs levels in octogenarians in comparison to patients younger than 70 years and 2)percentage of patients, in each group, who have target DTT or AFXa ( predicted) at steady state.
Potential significance of the study:
The results of the study may provide new data on DOACs levels in octogenarians and thus would either support current recommendations or set the ground for further studies aim to optimize DOACs dosage in this vulnerable population.
详细描述
A cross sectional, prospective study of hospitalized and ambulatory patients, who are treated with DOACs for AF.
Patient population Candidate for the study will be patients older than 80 years (octogenarians) and those ≤70 years who are 1) admitted to the Internal Medicine division in Rabin Medical Center or to Beit Rivka rehabilitation hospital who are on treatment of DOAC prior to their hospitalization \ rehabilitation , 2) hospitalized patients in whom DOAC will be initiated during hospitalization and 3) referred ambulatory patients on DOACs. Each potential patient will be screened for age and other risk factors for bleeding (specifically those that requires dose adjustment such as renal failure, weight, potentially interacting drugs) under DOAC treatment.
Study cohorts
The investigators plan to assess DOACS levels among 120 patients who will be treated by one of the three available agents:
Group 1) sixty patients who will be treated with the direct Xa inhibitor Apixaban - 40 octogenarians and 20 younger than 70 years.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Octogenarian group : Age ≥ 80 years.
- •Younger age group: Age ≤ 70 years.
- •Previous diagnosis of non-valvular atrial fibrillation / flutter or new diagnosis, documented by electrocardiography
- •CHA2DS2-VASc score ≥
- •Hemodynamically stable patients (i.e., without cardiogenic shock or circulatory collapse).
- •Receiving DOACs for at least 4 days.
- •Stable renal function.
排除标准
- •Patients who are expected to stop DOACs within the 4-8 days (i.e. planned operation or invasive procedure)
- •Patients who require dose adjustment of DOACs based on clinical judgment and not on manufacturer recommendations (i.e. acute renal function deterioration with GFR less than 30 ml/min, need for dual antiplatelet therapy)
- •History of gastrointestinal conditions that could significantly impact drug absorption (such as Crohn's disease, gastrectomy).
- •A history of recent drug or alcohol abuse
- •Concomitant treatment with combined strong P-gp inhibitors and CYP3A4 inhibitors drugs (such as: grapefruit juice, itraconazole, lopinavir/ritonavir, clarithromycin, ritonavir, ketoconazole, indinavir/ritonavir, conivaptan).
- •Concomitant treatment with combined strong P-gp inducers and CYP3A4 inducers drugs (such as: avasimibe ,carbamazepine, phenytoin, phenobarbital, rifampin, St John's wort)
- •Estimated glomerular filtration rate < 30 ml/min
- •Patients with elevated liver enzymes ALT/AST > 3 x ULN or total bilirubin ≥ 1.5 x ULN.
- •Weight > 120 kg.
- •Pregnant woman.
结局指标
主要结局
Diluted thrombin time (DTT) for Dabigatran
时间窗: trough and peak levels after at least 4 days of drug intake (trough will be taken just before the morning dose and peak levels 2 hours after the intake of Dabigatran)
anti FXa-activity for Apixaban and Rivaroxaban
时间窗: trough and peak levels after at least 4 days of drug intake (trough will be taken just before the morning dose and peak levels 3 hours after the intake of Apixaba/Rivaroxaban)
次要结局
未报告次要终点
研究者
shmuel fuchs
Professor
Rabin Medical Center