PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 243
- 试验地点
- 8
- 主要终点
- Change in noncalcified coronary artery plaque volume (NCPV)
研究概览
简要总结
This is a multi-center study conducted at 8 sites in 2 countries (Singapore, New Zealand). Patients with an acute myocardial infarction (AMI) were randomized in a ratio of 1:1 ratio to receive AZD5718 (Atuliflapon) 125 mg or placebo for 12 months to assess the efficacy of AZD5718 to prevent coronary plaque progression as measured on serial computer tomographic coronary angiography.
详细描述
PASSIVATE is a randomized, double-blind, placebo-controlled Phase IIa trial that investigates how 12 months of treatment with AZD5718 modifies coronary plaque volume. Patients with recent STEMI or NSTEMI will receive an additional oral dose of AZD5718 (or placebo) once daily to standard clinical care for 12 months. The primary hypothesis being tested in PASSIVATE is that 12 months of treatment with AZD5718 attenuates the progression of non-calcified plaque (NCP) volume on serial computed tomography coronary angiography (CTCA) studies.
Patients who gave consent (within 60 days after their index event) will undergo a CTCA scan and start treatment (AZD5718 or Placebo). The treatment duration will be 12 months. During the treatment period, patients will come to the clinic for follow-ups. At 12 months (end treatment), the patients will undergo their 2nd CTCA scan. A follow-up visit will be performed 4 weeks after the last dose in order to ensure the safety and well-being of the patients.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
CT coronary angiogram core laboratory
入排标准
- 年龄范围
- 21 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •hospitalised for STEMI or non-STEMI, as defined by the 4th universal definition of MI
- •underwent coronary angiography during the index hospitalisation showing at least one epicardial coronary artery with ≥50% stenosis and a 2nd epicardial coronary artery with ≥20% stenosis on the coronary angiogram
- •Body Mass Index (BMI) ≥18 to ≤40 kg/m2
- •White Blood Cell count ≥ 7.0 X 103/uL during admission
排除标准
- •Prior coronary artery bypass grafting (CABG)
- •CABG planned within 12 months of admission
- •Known history of drug or alcohol abuse within 5 years of screening
- •History of QT prolongation associated with other medications that required discontinuation of that medication
- •Congenital long QT syndrome
- •Systolic blood pressure persistently <90 mm Hg or HR<40 beats per minute at time of enrolment
- •ALT >2 x ULN, cirrhosis, recent hepatitis, or positive screening test for hepatitis B (hepatitis B surface antigen) or other viral hepatitis
- •Uncontrolled Type 1 or Type 2 DM defined as HbA1c >10% or 74.9 mmol/mol (by IFCC)
- •Any planned coronary revascularisation, valve surgery, or cardiac resynchronisation within 7 months after randomisation
- •Any concomitant medications known to be associated with Torsades de Pointes or potent inducers of cytochrome P450 3A4 (CYP3A4)
- •Planned treatment with zileuton, leukotriene receptor antagonists (e.g., montelukast) during trial
- •Participated in another interventional clinical study with an investigational pharmaceutical product during the last 3 months
- •Known hypersensitivity to drugs with a similar chemical structure or class of study drugs or any of the excipients of the product
- •Known conditions that either increase the risk of performing the CT or make the procedure technically impractical
- •No severe asthma attack that require emergency treatment or hospitalisation in the past 6 months
- •Had severe course of COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated), and/or had a confirmed case of COVID-19 within 4 weeks of Screening Visit
研究组 & 干预措施
AZD5718
Patients will receive once daily oral dose of AZD5718 for 12 months
干预措施: AZD5718 (Drug)
Placebo
Patients will receive once daily oral dose of placebo matched to AZD5718 for 12 months
干预措施: Placebo (Drug)
结局指标
主要结局
Change in noncalcified coronary artery plaque volume (NCPV)
时间窗: Baseline (before treatment) and after 12 months of treatment
Percent change in NCPV (in mm3), as assessed by CT coronary angiography, from baseline (before treatment) to after 12-month of treatment
次要结局
- Change in CT peri vascular (coronary) adipose tissue (PVAT)(Baseline (before treatment) and after 12 months of treatment)
- Change in total plaque volume (mm3)(Baseline (before treatment) and after 12 months of treatment)
- Echocardiographic assessment: Change in left ventricular ejection fraction (LVEF)(Baseline (before treatment) and after 12 months of treatment)
- Change in levels of urinary LTE4 (u-LTE4)(12 months)
研究者
Mark Chan
Associate Professor
National University Heart Centre, Singapore