Perfusion Estimation for Optimal Revascularization and Medical Therapy in Chronic Coronary Syndrome - a Randomized Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 570
- 试验地点
- 2
- 主要终点
- Symptomatic relief
研究概览
简要总结
We will establish a cohort of 570 symptomatic chronic coronary syndrome patients undergoing 15O-water PET and assess their symptoms through repeated questionnaires. Two hundred patients with abnormal perfusion will be randomized to immediate or delayed referral to invasive coronary angiography with concomitant optimization of guideline-directed medical therapy with repeated 15O-water PET and questionnaires at 3 and 6 months. The primary objective is to compare the potential benefit of early invasive coronary angiography (ICA) versus guideline directed medical therapy (GDMT) on symptomatic relief defined as freedom of angina after 3 months following a positive [15O]H2O cardiac PET/CT in patients with symptomatic chronic coronary syndrome.
详细描述
BACKGROUND:
Ischemic heart disease (IHD) is highly prevalent in Western countries and an emerging disease in developing countries around the globe. While the Danish incidence rate of IHD for both females and males has been declining during the last 15 years, the prevalence has stabilized at 165,000 patients in 2018 due to enhanced survival.
Ischemic heart disease is caused by atherosclerotic plaque formation in the epicardial coronary arteries, abnormalities in the coronary microcirculation, spasms in the vessel wall, or a combination thereof. This may result in chest discomfort or dyspnoea leading to frequent primary care consultations and admissions on the suspicion of acute coronary syndrome. To emphasize the chronic nature of the disease, the European Society of Cardiology has replaced the previous nomenclature of stable coronary artery disease with chronic coronary syndrome (CCS) in their latest guidelines from 2019.
When cardiac imaging is used to diagnose and select treatment in patients with CCS, guidelines recommend non-invasive functional imaging modalities in patients with an intermediate or high clinical likelihood of IHD or in patients with prior revascularization. In patients with prior myocardial infarction or percutaneous coronary intervention, studies have found higher diagnostic accuracy of [15O]H2O cardiac PET/CT with measurement of absolute quantification of myocardial perfusion to diagnose obstructive coronary artery disease compared with single-photon emission computed tomography and magnetic resonance imaging. Current European guidelines recommend myocardial revascularization in addition to guideline-directed medical therapy (GDMT) in CCS patients with large areas of ischemia (≥ 10%) in the left ventricle to improve prognosis.
Since the publication of these guidelines, a large randomized trial of initial invasive versus conservative strategy in patients with moderate-severe ischemia on stress testing has been published with no observed prognostic benefit of an initial invasive strategy in these patients. However, patients assigned to an initial invasive strategy had a greater improvement in angina-related health status as compared with a conservative strategy, with larger differences observed in patients who were more symptomatic at baseline. The study is limited by the high use of stress ECG (25% of participants) which has a very low diagnostic power and the high proportion of asymptomatic participants at baseline (35%).
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
- None
盲法说明
Patients will be blinded to the specific result of the initial [15O]H2O cardiac PET/CT. The result will be reported as normal, abnormal, or suspicion of unprotected left main coronary stenosis (exclusion criteria) until the termination of the study. Investigators and invasive coronary angiography operators are not blinded to the specific result of the initial [15O]H2O cardiac PET/CT in order to evaluate clinical indication for invasive coronary angiography. The coronary CT angiography will only be evaluated for unprotected left main coronary artery stenosis - the rest of the coronary CT angiography as well as the two additional [15O]H2O cardiac PET/CT scans at 3 and 6 months assessment will only be analyzed after the termination of the study. Investigators will be blinded to the results of baseline, 3, and 6 month questionnaires and walking distances until the termination of the study.
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
- •Age > 18 years
- •Willing to participate and able to understand, read and sign the informed consent document before the planned procedure
- •Known ischemic heart disease defined as one of the following
- •Previous myocardial infarction, percutaneous coronary intervention or coronary artery bypass grafting
- •Previous coronary computed tomography angiography or invasive coronary angiography documenting atherosclerosis.
- •Undergoing clinically indicated [15O]H2O cardiac PET/CT due to chest discomfort or dyspnea as angina equivalent
- •Additional inclusion criteria for randomized trial:
- •Initial [15O]H2O cardiac PET/CT with abnormal perfusion defined as all of the following
- •Hyperemic myocardial blood flow (hMBF) ≤2.3 mL/min/g in at least two adjacent myocardial segments
- •Relative hMBF ≤ 65% in at least two adjacent segments as compared with the mean hMBF of the two adjacent segments with the highest mean hMBF
- •Tissue perfusion defect extent ≥ 5% based on indices of relative hypoperfusion
- •Clinical indication for invasive coronary angiography decided at a multidisciplinary conference between consultants in nuclear medicine and cardiology
排除标准
- •Ongoing acute coronary syndrome or acute coronary syndrome within 30 days
- •Contraindications for adenosine
- •Severe asthma
- •Advanced atrioventricular block without pacemaker
- •Severe aortic stenosis
- •Patients not able to breath hold (severe COPD/asthma)
- •Pregnant women, including women who are potentially pregnant or lactating
- •Allergy to iomeron
- •Life expectancy of less than 2 years
- •Severe valvular disease
- •Reduced kidney function with an estimated glomerular filtrations rate <40 ml/min
- •Inability to consent
- •Additional exclusion criteria for randomized trial:
- •Unprotected left main coronary artery stenosis on coronary CT angiography
- •Very large perfusion defect on initial [15O]H2O cardiac PET/CT indicating left main coronary artery stenosis or balanced ischemia defined as tissue perfusion defect extent based on indices of absolute hMBF ≥ 20% in two or more myocardial territories supplied by coronary arteries with an Agatston calcium score ≥ 300
结局指标
主要结局
Symptomatic relief
时间窗: After 3 months following a positive [15O]H2O cardiac PET/CT
Seattle Angina Questionnaire-7 angina frequency score = 100 (0-100 with higher scores indicating less frequent angina)
次要结局
- Angina frequency(3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT)
- Dyspnea(3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT)
- Work Ischemic Symptom score(3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT)
- Coronary revascularization(10 years after randomization or index [15O]H2O cardiac PET/CT)
- All-cause mortality(10 years after randomization or index [15O]H2O cardiac PET/CT)
- Hyperemic myocardial blood flow(3 and 6 months after randomization)
- Coronary flow capacity(3 and 6 months after randomization)
- Health status(3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT)
- Cardiovascular mortality(10 years after randomization or index [15O]H2O cardiac PET/CT)
- Unstable angina(10 years after randomization or index [15O]H2O cardiac PET/CT)
- Unplanned hospitalization(10 years after randomization or index [15O]H2O cardiac PET/CT)
- Use of CCTA, MPI, and ICA(10 years after randomization or index [15O]H2O cardiac PET/CT)
- Quality of life-score(3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT)
- Myocardial flow reserve(3 and 6 months after randomization)
- Myocardial infarction(10 years after randomization or index [15O]H2O cardiac PET/CT)
- De novo heart failure(10 years after randomization or index [15O]H2O cardiac PET/CT)
- Walking capacity(3 and 6 months after randomization)
- Physical limitation(3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT)