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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05865600
Other study ID # 1-10-72-185-22
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date May 23, 2023
Est. completion date September 1, 2025

Study information

Verified date May 2023
Source Gødstrup Hospital
Contact Jacob H Søby, MD
Phone 61659131
Email jasoeb@rm.dk
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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%). It is unknown whether the results of MPI with absolute quantification of myocardial perfusion can improve the selection of patients with an additional symptomatic benefit of an initial invasive strategy compared with GDMT. METHODS: Patients with symptomatic CCS referred for clinically indicated [15O]H2O cardiac PET/CT will be included in a prospective cohort and assessed with questionnaires at baseline, 3, 6, 12, 60, and 120 months. Clinical outcomes will be assessed through national registries. Patients with abnormal perfusion and a clinical indication for ICA will undergo coronary CT angiography and a six-minute walking test. Hereafter, they will be randomized 1:1 to immediate referral to ICA or 3 months delayed referral to ICA. Both groups will undergo optimization of GDMT with consultations every two weeks. At 3 and 6 months, both groups will undergo repeated questionnaires, [15O]H2O cardiac PET/CT and a six-minute walking test. Enrollment in the cohort study and randomized trial will continue until 200 randomized patients have reached the 3 months assessment.


Recruitment information / eligibility

Status Recruiting
Enrollment 570
Est. completion date September 1, 2025
Est. primary completion date December 1, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Age > 18 years 2. Willing to participate and able to understand, read and sign the informed consent document before the planned procedure 3. Known ischemic heart disease defined as one of the following 1. Previous myocardial infarction, percutaneous coronary intervention or coronary artery bypass grafting 2. Previous coronary computed tomography angiography or invasive coronary angiography documenting atherosclerosis. 4. Undergoing clinically indicated [15O]H2O cardiac PET/CT due to chest discomfort or dyspnea as angina equivalent Additional inclusion criteria for randomized trial: 5. Initial [15O]H2O cardiac PET/CT with abnormal perfusion defined as all of the following 1. Hyperemic myocardial blood flow (hMBF) =2.3 mL/min/g in at least two adjacent myocardial segments 2. 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 3. Tissue perfusion defect extent = 5% based on indices of relative hypoperfusion 6. Clinical indication for invasive coronary angiography decided at a multidisciplinary conference between consultants in nuclear medicine and cardiology Exclusion Criteria: 1. Ongoing acute coronary syndrome or acute coronary syndrome within 30 days 2. Contraindications for adenosine 1. Severe asthma 2. Advanced atrioventricular block without pacemaker 3. Severe aortic stenosis 3. Patients not able to breath hold (severe COPD/asthma) 4. Pregnant women, including women who are potentially pregnant or lactating 5. Allergy to iomeron 6. Life expectancy of less than 2 years 7. Severe valvular disease 8. Reduced kidney function with an estimated glomerular filtrations rate <40 ml/min 9. Inability to consent Additional exclusion criteria for randomized trial: 10. Unprotected left main coronary artery stenosis on coronary CT angiography 11. 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

Study Design


Intervention

Other:
Optimization of guideline-directed medical therapy
Consultation every second week with optimization of guideline-directed medical therapy according to 2019 ESC guidelines on chronic coronary syndrome. Focus will be on risk-factor modification and anti-anginal medication with the treatment aim to achieve freedom from angina and dyspnea with a heart rate at rest = 60 beats/min and systolic blood pressure > 100 mmHg.
Diagnostic Test:
Immediate referral for invasive coronary angiography
Immediate referral for invasive coronary angiography
3-months delayed referral for invasive coronary angiography
3-months delayed referral for invasive coronary angiography
Other:
Standard of care
Standard of care

Locations

Country Name City State
Denmark Gødstrup Hospital Herning Central Denmark Region

Sponsors (1)

Lead Sponsor Collaborator
Gødstrup Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type Measure Description Time frame Safety issue
Primary Symptomatic relief Seattle Angina Questionnaire-7 angina frequency score = 100 (0-100 with higher scores indicating less frequent angina) After 3 months following a positive [15O]H2O cardiac PET/CT
Secondary Walking capacity Meters walked in six-minute walking test 3 and 6 months after randomization
Secondary Angina frequency Seattle Angina Questionnaire-7 angina frequency score (0-100 with higher scores indicating less frequent angina) 3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT
Secondary Physical limitation Seattle Angina Questionnaire-7 physical limitation score (0-100 with higher scores indicating less physical limitation) 3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT
Secondary Quality of life-score Seattle Angina Questionnaire-7 quality of life score (0-100 with higher scores indicating better quality of life) 3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT
Secondary Health status Seattle Angina Questionnaire-7 summary score (0-100 where 0 denotes the lowest reportable health status and 100 the highest) 3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT
Secondary Dyspnea Rose Dyspnea Scale. Scores range from 0 to 4, where 0 indicates no dyspnea with activity and 4 indicates significant limitations due to dyspnea 3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT
Secondary Work Ischemic Symptom score Work Ischemic Symptom score summary score. The scoring system is currently under development. 3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT
Secondary Hyperemic myocardial blood flow Global and territorial hyperemic myocardial blood flow (ml/g/min) of perfusable myocardium on [15O]H2O cardiac PET/CT. 3 and 6 months after randomization
Secondary Myocardial flow reserve Global and territorial myocardial flow reserve (unitless measure) on [15O]H2O cardiac PET/CT. 3 and 6 months after randomization
Secondary Coronary flow capacity Coronary flow capacity incorporates hyperemic myocardial blood flow and myocardial flow reserve into a 5-point ordinal scale ranging from myocardial steal indicating very poor coronary flow capacity to normal coronary flow capacity. All data is derived from [15O]H2O cardiac PET/CT. 3 and 6 months after randomization
Secondary Coronary revascularization Percutaneous coronary intervention and/or coronary artery bypass grafting 3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Secondary Coronary revascularization Percutaneous coronary intervention and/or coronary artery bypass grafting 10 years after randomization or index [15O]H2O cardiac PET/CT
Secondary Myocardial infarction All myocardial infarctions 3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Secondary Myocardial infarction All myocardial infarctions 10 years after randomization or index [15O]H2O cardiac PET/CT
Secondary All-cause mortality All deaths 3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Secondary All-cause mortality All deaths 10 years after randomization or index [15O]H2O cardiac PET/CT
Secondary Cardiovascular mortality All cardiovascular deaths 3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Secondary Cardiovascular mortality All cardiovascular deaths 10 years after randomization or index [15O]H2O cardiac PET/CT
Secondary Unstable angina Unstable angina 3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Secondary Unstable angina Unstable angina 10 years after randomization or index [15O]H2O cardiac PET/CT
Secondary Unplanned hospitalization Any hospitalization requiring overnight stay not electively planned 3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Secondary Unplanned hospitalization Any hospitalization requiring overnight stay not electively planned 10 years after randomization or index [15O]H2O cardiac PET/CT
Secondary De novo heart failure New diagnosis of heart failure 3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Secondary De novo heart failure New diagnosis of heart failure 10 years after randomization or index [15O]H2O cardiac PET/CT
Secondary Use of CCTA, MPI, and ICA Use of coronary CT angiography, myocardial perfusion imaging and invasive coronary angiography 10 years after randomization or index [15O]H2O cardiac PET/CT
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