Treatment of Cardiovascular Disease With Low Dose Rivaroxaban in Advanced Chronic Kidney Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,753
- 试验地点
- 119
- 主要终点
- Risk of Major Adverse Cardiac Event (MACE)
研究概览
简要总结
The TRACK trial is an investigator-initiated, multicentre, prospective, randomised, quadruple-blind (participant, healthcare provider, data collector, outcomes assessor), placebo-controlled trial. TRACK is a global trial and will be conducted in renal units that provide comprehensive CKD care. Approximately 2000 participants will be recruited.
The TRACK trial will assess a strategy of administering low dose rivaroxaban to reduce the risk of major adverse cardiac event (MACE) in people with Chronic Kidney Disease (CKD) stages 4 or 5 or dialysis-dependent kidney failure, and elevated cardiovascular (CV) risk (marked by a history of CAD or PAD, or non-haemorrhagic non-lacunar stroke OR diabetes mellitus OR age ≥65 years).
详细描述
Background and Rationale Chronic Kidney Disease (CKD) is a major international health burden. Despite the unacceptably high burden of cardiovascular disease (CVD) and associated mortality, trial-data on the management of CVD in people with advanced stages of CKD and dialysis-dependent kidney failure are sparse. Risk of bleeding in CKD and dialysis-dependent kidney failure is increased when compared to the general population. Anticoagulant agents, such as rivaroxaban, are a core intervention in the prevention of CVD in the general population. Nevertheless, to mitigate trial risks, 90% of the trials evaluating this form of intervention exclude these patient populations.
The TRACK trial will evaluate the effect of low dose rivaroxaban in patients with CKD dialysis-dependent kidney failure. Other trials have demonstrated that rivaroxaban reduces the risk of major cardio-vascular outcomes in high risk patients, and the limited data showed that CKD status did not significantly affect this result.
Hypothesis Compared to placebo, low dose rivaroxaban reduces the risk of major adverse cardiac event (MACE) in people with CKD stages 4 or 5 or dialysis-dependent kidney failure, and elevated cardiovascular (CV) risk (marked by a history of CAD or PAD, or non-haemorrhagic non-lacunar stroke OR diabetes mellitus OR age ≥65 years).
Objectives The primary objective is to determine whether low dose rivaroxaban, compared to placebo, significantly reduces the risk of a composite outcome of;
- CV death,
- non-fatal myocardial infarction,
- stroke, or
- peripheral artery disease (PAD) events
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Quadruple-blind, Placebo-controlled
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •People able to provide informed consent who meet all of the following inclusion criteria:
- •Age ≥18 years,
- •Kidney Failure on haemodialysis or peritoneal dialysis, or CKD stage 4 or 5 (eGFR ≤29 mL/min/1.73 m2) not receiving renal replacement therapy,
- •Elevated cardiovascular risk, defined by at least one of the following:
- •History of Coronary Artery Disease (CAD) or PAD or non-haemorrhagic non-lacunar stroke, or
- •Diabetes mellitus, or
- •Age ≥65 years.
排除标准
- •Potential participants must have none of the following exclusion criteria at the time of study enrolment:
- •Mechanical/prosthetic heart valve (does not include bioprosthetic valves that do not require therapeutic anticoagulation),
- •Indication for, or contraindication to, anticoagulant therapy,
- •High bleeding risk including any coagulopathy,
- •Lesion or condition considered to be a significant risk of major bleeding,
- •Major bleeding episode in the 30 days prior to study enrolment, or any active and clinically significant bleeding,
- •Current treatment with P2Y12 inhibitors/adenosine diphosphate (ADP) receptor inhibitors (clopidogrel, prasugrel, ticagrelor, cangrelor) or phosphodiesterase inhibitors (dipyridamole), where the treating physician or patient does not wish to stop these medications,
- •Concurrent treatment with strong inhibitors of combined CYP3A4 and P-glycoprotein; or strong inducers of CYP3A4,
- •Any stroke within 1 month prior to enrolment,
- •Any previous history of a haemorrhagic or lacunar stroke,
- •Severe heart failure with known ejection fraction <30% or New York Heart Association class III or IV symptoms,
- •History of hypersensitivity or known contraindication to rivaroxaban,
- •Uncontrolled hypertension (systolic BP ≥180 mm Hg or diastolic BP ≥110 mm Hg), at the time of screening
- •Haemoglobin <90 g/L, or platelet count <100 x 109/L,
- •Significant liver disease (defined as Child-Pugh Class B or C) or Alanine Aminotransferase (ALT) >3 times upper normal limit,
- •Kidney transplant recipients with a functioning allograft, or scheduled for living-donor kidney transplant surgery,
- •All countries except Europe: Pregnancy or intention to become pregnant or breast-feeding; Europe only: Women who are not in a postmenopausal state, where postmenopausal is defined as no menses for 12 months without alternative medical causes,
- •Inability to understand or comply with the requirements of the study.
研究组 & 干预措施
Rivaroxaban
Rivaroxaban 2.5mg, twice daily.
干预措施: Rivaroxaban 2.5 Mg Oral Tablet (Drug)
Placebo
Matched placebo, twice daily.
干预措施: Placebo (Other)
结局指标
主要结局
Risk of Major Adverse Cardiac Event (MACE)
时间窗: 5 years or trial closure
To determine whether the intervention, compared to placebo, changes the risk of a composite outcome of; * CV death, * non-fatal myocardial infarction, * stroke, or * peripheral artery disease (PAD) events
次要结局
- Incidence of Venous Thromboembolism(5 years or trial closure)
- Composite outcome of cardiovascular death, non-fatal myocardial infarction, or stroke.(5 years or trial closure)
- Incidence of Cardiovascular Death(5 years or trial closure)
- Incidence of Non-Fatal Myocardial Infarction(5 years or trial closure)
- Composite outcome of all-cause death, non-fatal myocardial infarction, stroke, or PAD events.(5 years or trial closure)
- Composite outcome of all-cause death, non-fatal myocardial infarction, or stroke.(5 years or trial closure)
- Incidence of Stroke(5 years or trial closure)
- Incidence of PAD Events(5 years or trial closure)
- Net Clinical Benefit - incidence of MACE & Bleeding(5 years or trial closure)