An interventional study of Optimization of guideline-directed medical therapy and Immediate referral for invasive coronary angiography in Chronic Coronary Syndrome, Myocardial Ischemia and Stable Angina, sponsored by Gødstrup Hospital. Recruiting at 1 site in Denmark. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-12-10.
Sponsored by Gødstrup Hospital · Not applicable, Interventional, and Treatment
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.
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.
1,123 studies on the registry are indexed under Myocardial Ischemia; 177 are open to participants now.
This study's planned enrollment of 570 is above the median of 116 across 622 interventional studies indexed under Myocardial Ischemia.
Browse Myocardial Ischemia studies →Gødstrup Hospital is the lead sponsor of 24 studies on the registry; 14 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Known ischemic heart disease defined as one of the following
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
Exclusion Criteria:
for adenosine
Inability to consent
Additional exclusion criteria for randomized trial:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All patients with symptomatic chronic coronary syndrome undergoing clinically referred \[15O\]H2O cardiac PET/CT will be included in a prospective cohort with repeated symptom questionnaires and outcomes registered in national registries. A total of 570 patients are expected to be included in order to have 200 randomized patients reaching the 3-month assessment
Other: Standard of care
Patients with abnormal perfusion on \[15O\]H2O cardiac PET/CT and clinical indication for invasive coronary angiography randomized to immediate referral for invasive coronary angiography with concomitant optimization of guideline-directed medical therapy. Enrollment will continue until a total of 200 randomized patients reach the 3-month assessment.
Other: Optimization of guideline-directed medical therapy · Diagnostic Test: Immediate referral for invasive coronary angiography
Patients with abnormal perfusion on \[15O\]H2O cardiac PET/CT and clinical indication for invasive coronary angiography randomized to 3-months delayed referral for invasive coronary angiography with concomitant optimization of guideline-directed medical therapy. Enrollment will continue until a total of 200 randomized patients reach the 3-month assessment.
Other: Optimization of guideline-directed medical therapy · Diagnostic Test: 3-months delayed referral for invasive coronary angiography
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.
Immediate referral for invasive coronary angiography
3-months delayed referral for invasive coronary angiography
Standard of care
Symptomatic relief
Seattle Angina Questionnaire-7 angina frequency score = 100 (0-100 with higher scores indicating less frequent angina)
Time frame: After 3 months following a positive [15O]H2O cardiac PET/CT
Walking capacity
Meters walked in six-minute walking test
Time frame: 3 and 6 months after randomization
Angina frequency
Seattle Angina Questionnaire-7 angina frequency score (0-100 with higher scores indicating less frequent angina)
Time frame: 3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT
Physical limitation
Seattle Angina Questionnaire-7 physical limitation score (0-100 with higher scores indicating less physical limitation)
Time frame: 3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT
Quality of life-score
Seattle Angina Questionnaire-7 quality of life score (0-100 with higher scores indicating better quality of life)
Time frame: 3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT
Health status
Seattle Angina Questionnaire-7 summary score (0-100 where 0 denotes the lowest reportable health status and 100 the highest)
Time frame: 3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT
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
Time frame: 3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT
Work Ischemic Symptom score
Work Ischemic Symptom score summary score. The scoring system is currently under development.
Time frame: 3, 6, 12, 60, and 120 months after randomization or index [15O]H2O cardiac PET/CT
Hyperemic myocardial blood flow
Global and territorial hyperemic myocardial blood flow (ml/g/min) of perfusable myocardium on \[15O\]H2O cardiac PET/CT.
Time frame: 3 and 6 months after randomization
Myocardial flow reserve
Global and territorial myocardial flow reserve (unitless measure) on \[15O\]H2O cardiac PET/CT.
Time frame: 3 and 6 months after randomization
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.
Time frame: 3 and 6 months after randomization
Coronary revascularization
Percutaneous coronary intervention and/or coronary artery bypass grafting
Time frame: 3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Coronary revascularization
Percutaneous coronary intervention and/or coronary artery bypass grafting
Time frame: 10 years after randomization or index [15O]H2O cardiac PET/CT
Myocardial infarction
All myocardial infarctions
Time frame: 3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Myocardial infarction
All myocardial infarctions
Time frame: 10 years after randomization or index [15O]H2O cardiac PET/CT
All-cause mortality
All deaths
Time frame: 3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
All-cause mortality
All deaths
Time frame: 10 years after randomization or index [15O]H2O cardiac PET/CT
Cardiovascular mortality
All cardiovascular deaths
Time frame: 3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Cardiovascular mortality
All cardiovascular deaths
Time frame: 10 years after randomization or index [15O]H2O cardiac PET/CT
Unstable angina
Unstable angina
Time frame: 3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Unstable angina
Unstable angina
Time frame: 10 years after randomization or index [15O]H2O cardiac PET/CT
Unplanned hospitalization
Any hospitalization requiring overnight stay not electively planned
Time frame: 3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Unplanned hospitalization
Any hospitalization requiring overnight stay not electively planned
Time frame: 10 years after randomization or index [15O]H2O cardiac PET/CT
De novo heart failure
New diagnosis of heart failure
Time frame: 3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
De novo heart failure
New diagnosis of heart failure
Time frame: 10 years after randomization or index [15O]H2O cardiac PET/CT
Use of CCTA, MPI, and ICA
Use of coronary CT angiography, myocardial perfusion imaging and invasive coronary angiography
Time frame: 10 years after randomization or index [15O]H2O cardiac PET/CT
Plan to share: No — Individual participant data will not be readily available due to Danish legislation. Data can be shared upon reasonable request if a research protocol is submitted to the investigators and approval for data sharing is obtained via Danish authorities.
No publications or documents are linked to this record.
Started May 2023 (actual). Primary completion is estimated for Sep 2026, 39 months after the start.
Of 155 non-industry interventional studies with no phase under Myocardial Ischemia, half reached primary completion within 33 months of starting (the median), counting those still running; a quarter within 15 and three quarters within 56. This study's planned 39 months is above that.
Counting every sponsor, half of 192 studies reached it within 34 months; a quarter within 15 and three quarters within 58.
How these figures are worked out, and which studies are left out of them.
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