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Perfusion Estimation For Optimal Treatment Strategy in Chronic Coronary Syndrome (PERFORM-CCS)

Primary Purpose

Chronic Coronary Syndrome, Myocardial Ischemia, Stable Angina

Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Optimization of guideline-directed medical therapy
Immediate referral for invasive coronary angiography
3-months delayed referral for invasive coronary angiography
Standard of care
Sponsored by
Gødstrup Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Coronary Syndrome focused on measuring Myocardial Ischemia, Angina Pectoris, Coronary Artery Disease, Coronary Angiography, Computed Tomography Angiography, Myocardial Perfusion Imaging

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 Exclusion Criteria: 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

Sites / Locations

  • Gødstrup HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Experimental

Experimental

Arm Label

Cohort study

Immediate referral to invasive coronary angiography

Delayed referral to invasive coronary angiography

Arm Description

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

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.

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.

Outcomes

Primary Outcome Measures

Symptomatic relief
Seattle Angina Questionnaire-7 angina frequency score = 100 (0-100 with higher scores indicating less frequent angina)

Secondary Outcome Measures

Walking capacity
Meters walked in six-minute walking test
Angina frequency
Seattle Angina Questionnaire-7 angina frequency score (0-100 with higher scores indicating less frequent angina)
Physical limitation
Seattle Angina Questionnaire-7 physical limitation score (0-100 with higher scores indicating less physical limitation)
Quality of life-score
Seattle Angina Questionnaire-7 quality of life score (0-100 with higher scores indicating better quality of life)
Health status
Seattle Angina Questionnaire-7 summary score (0-100 where 0 denotes the lowest reportable health status and 100 the highest)
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
Work Ischemic Symptom score
Work Ischemic Symptom score summary score. The scoring system is currently under development.
Hyperemic myocardial blood flow
Global and territorial hyperemic myocardial blood flow (ml/g/min) of perfusable myocardium on [15O]H2O cardiac PET/CT.
Myocardial flow reserve
Global and territorial myocardial flow reserve (unitless measure) on [15O]H2O cardiac PET/CT.
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.
Coronary revascularization
Percutaneous coronary intervention and/or coronary artery bypass grafting
Coronary revascularization
Percutaneous coronary intervention and/or coronary artery bypass grafting
Myocardial infarction
All myocardial infarctions
Myocardial infarction
All myocardial infarctions
All-cause mortality
All deaths
All-cause mortality
All deaths
Cardiovascular mortality
All cardiovascular deaths
Cardiovascular mortality
All cardiovascular deaths
Unstable angina
Unstable angina
Unstable angina
Unstable angina
Unplanned hospitalization
Any hospitalization requiring overnight stay not electively planned
Unplanned hospitalization
Any hospitalization requiring overnight stay not electively planned
De novo heart failure
New diagnosis of heart failure
De novo heart failure
New diagnosis of heart failure
Use of CCTA, MPI, and ICA
Use of coronary CT angiography, myocardial perfusion imaging and invasive coronary angiography

Full Information

First Posted
May 2, 2023
Last Updated
May 23, 2023
Sponsor
Gødstrup Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05865600
Brief Title
Perfusion Estimation For Optimal Treatment Strategy in Chronic Coronary Syndrome
Acronym
PERFORM-CCS
Official Title
Perfusion Estimation for Optimal Revascularization and Medical Therapy in Chronic Coronary Syndrome - a Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 23, 2023 (Actual)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
September 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gødstrup Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Coronary Syndrome, Myocardial Ischemia, Stable Angina, Coronary Artery Disease
Keywords
Myocardial Ischemia, Angina Pectoris, Coronary Artery Disease, Coronary Angiography, Computed Tomography Angiography, Myocardial Perfusion Imaging

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
All eligible patients are included in a prospective cohort with repeated questionnaires. Patients with abnormal perfusion and clinical indication for invasive coronary angiography are randomized 1:1 in permuted blocks with random varying sizes of 4,6 and 8 to either immediate invasive coronary angiography or delayed invasive coronary angiography via a standard computerized random-number generator stratified for age ≥70 years and sex (REDcap). Proper concealment of randomization is obtained by the use of an external randomization service (Clinical Trial Unit, Dept. of Clinical Medicine, Aarhus University, Denmark).
Masking
None (Open Label)
Masking Description
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.
Allocation
Randomized
Enrollment
570 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort study
Arm Type
Other
Arm Description
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
Arm Title
Immediate referral to invasive coronary angiography
Arm Type
Experimental
Arm Description
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.
Arm Title
Delayed referral to invasive coronary angiography
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Optimization of guideline-directed medical therapy
Intervention Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
Immediate referral for invasive coronary angiography
Intervention Description
Immediate referral for invasive coronary angiography
Intervention Type
Diagnostic Test
Intervention Name(s)
3-months delayed referral for invasive coronary angiography
Intervention Description
3-months delayed referral for invasive coronary angiography
Intervention Type
Other
Intervention Name(s)
Standard of care
Intervention Description
Standard of care
Primary Outcome Measure Information:
Title
Symptomatic relief
Description
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
Secondary Outcome Measure Information:
Title
Walking capacity
Description
Meters walked in six-minute walking test
Time Frame
3 and 6 months after randomization
Title
Angina frequency
Description
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
Title
Physical limitation
Description
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
Title
Quality of life-score
Description
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
Title
Health status
Description
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
Title
Dyspnea
Description
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
Title
Work Ischemic Symptom score
Description
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
Title
Hyperemic myocardial blood flow
Description
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
Title
Myocardial flow reserve
Description
Global and territorial myocardial flow reserve (unitless measure) on [15O]H2O cardiac PET/CT.
Time Frame
3 and 6 months after randomization
Title
Coronary flow capacity
Description
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
Title
Coronary revascularization
Description
Percutaneous coronary intervention and/or coronary artery bypass grafting
Time Frame
3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Title
Coronary revascularization
Description
Percutaneous coronary intervention and/or coronary artery bypass grafting
Time Frame
10 years after randomization or index [15O]H2O cardiac PET/CT
Title
Myocardial infarction
Description
All myocardial infarctions
Time Frame
3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Title
Myocardial infarction
Description
All myocardial infarctions
Time Frame
10 years after randomization or index [15O]H2O cardiac PET/CT
Title
All-cause mortality
Description
All deaths
Time Frame
3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Title
All-cause mortality
Description
All deaths
Time Frame
10 years after randomization or index [15O]H2O cardiac PET/CT
Title
Cardiovascular mortality
Description
All cardiovascular deaths
Time Frame
3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Title
Cardiovascular mortality
Description
All cardiovascular deaths
Time Frame
10 years after randomization or index [15O]H2O cardiac PET/CT
Title
Unstable angina
Description
Unstable angina
Time Frame
3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Title
Unstable angina
Description
Unstable angina
Time Frame
10 years after randomization or index [15O]H2O cardiac PET/CT
Title
Unplanned hospitalization
Description
Any hospitalization requiring overnight stay not electively planned
Time Frame
3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Title
Unplanned hospitalization
Description
Any hospitalization requiring overnight stay not electively planned
Time Frame
10 years after randomization or index [15O]H2O cardiac PET/CT
Title
De novo heart failure
Description
New diagnosis of heart failure
Time Frame
3 and 6 months after randomization or index [15O]H2O cardiac PET/CT
Title
De novo heart failure
Description
New diagnosis of heart failure
Time Frame
10 years after randomization or index [15O]H2O cardiac PET/CT
Title
Use of CCTA, MPI, and ICA
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jacob H Søby, MD
Phone
61659131
Ext
0045
Email
jasoeb@rm.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Morten Böttcher, Prof
Organizational Affiliation
University Clinic for Cardiovascular Research, Dept. of Cardiology, Gødstrup Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Gødstrup Hospital
City
Herning
State/Province
Central Denmark Region
ZIP/Postal Code
7400
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Morten Böttcher, Prof
Phone
25775134
Ext
0045
Email
morboett@rm.dk
First Name & Middle Initial & Last Name & Degree
Jacob H Søby, MD
Phone
61659131
Ext
0045
Email
jasoeb@rm.dk

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
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.

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Perfusion Estimation For Optimal Treatment Strategy in Chronic Coronary Syndrome

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