Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF): A Multicenter, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 675
- 试验地点
- 79
- 主要终点
- Peak VO2 during cardio-pulmonary exercise test (CPET);
研究概览
简要总结
This is a multicenter, randomized, placebo-controlled, 2-part study to evaluate the safety and efficacy of AT-001 in adult patients (N=675) with Diabetic Cardiomyopathy at high risk of progression to overt heart failure.
详细描述
The study consists of two consecutive parts: Part A and Part B. Part A will evaluate the safety and efficacy of two doses of AT-001 vs placebo. The primary objective of Part A is to demonstrate that AT-001 improves or prevents the decline of functional capacity in patients with Diabetic Cardiomyopathy. Part B is an extension of at least 12 months that will evaluate the safety and efficacy of chronic administration of AT-001 vs placebo in the same patients who had previously been evaluated in Part A. Assessments in Part B will include safety endpoints and exploratory clinical efficacy endpoints, i.e. death and hospitalization due to a cardiac event.
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)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 Diabetes Mellitus
- •Diabetic cardiomyopathy
- •Peak VO2 < 75% of predicted normal value based on age and gender
排除标准
- •Prior diagnosis or signs/symptoms of overt/symptomatic heart failure / stage C heart failure
- •Prior echocardiogrphic measurement of ejection fraction (EF) < 40%
- •Prior acute coronary syndrome (ACS), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), coronary artery disease (CAD) or stroke
- •Severe or moderate cardiac valve disease requiring intervention
- •Clinically significant arrhythmia
- •Prior diagnosis of congenital, infective, toxic, infiltrative, post-partum, or hypertrophic cardiomyopathy
- •Blood pressure > 140 mmHg (systolic) or > 90 mmHg (diastolic) at screening
- •HbA1c >8.5% at screening
- •Severe disease that would impact the performance of a cardio-pulmonary exercise test
研究组 & 干预措施
AT-001 High dose
The total daily doses will be of 3g. The dose selection and the frequency of dosing was based on the results of the phase 1/2 study demonstrating that 3g/day of AT-001 is capable of producing the maximum inhibition of the production of sorbitol (a pharmacodynamic biomarker of biological activity).
干预措施: AT-001 (Drug)
AT-001 Low Dose
The total daily doses will be of 2g. The dose selection and the frequency of dosing was based on the results of the phase 1/2 study demonstrating that 2g/day of AT-001 is capable of producing a sufficient inhibition of the production of sorbitol (a pharmacodynamic biomarker of biological activity).
干预措施: AT-001 (Drug)
Placebo Comparator
Placebo capsules will be used as comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Peak VO2 during cardio-pulmonary exercise test (CPET);
时间窗: 15 months after randomization]
Changes in Peak VO2 during cardio-pulmonary exercise test (CPET) from baseline to approximately Month 15 (15-18 months). A CPET may be repeated at approximately Month 27 (27-30 months).
次要结局
- Progression to overt heart failure (Stage C Heart Failure)(27 months after randomization)
- Changes in NT-proBNP(27 months after randomization)
- Changes in the modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score(27 months after randomization)