Clinical trial NCT04939207: Safety and Cost-efficiëncy of New Imaging Techniques in Patients Suspected of Coronary Artery Disease
Official title: Improving the Cost-effectiveness of Coronary Artery Disease Diagnosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Coronary Artery Disease
Keywords: Coronary artery disease
Angina pectoris
Coronary arteriosclerosis
CT scan
Cardiac catheterization
Coronary angiography
Myocardial fractional flow reserve
Lead sponsor: St. Antonius Hospital
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: UMC Utrecht
First posted: 2021-06-25
Enrollment: 825
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After coronary CT-scan, patients will be randomized in one of three possible study arms. One arm will receive additional CT-derived calculation of coronary blood flow, one arm will receive angiography-derived calculation of coronary blood flow and one arm will receive standard routine care. Standard care consists of coronary angiography and invasive coronary blood flow measurements. The results of these tests determine the need for treatment of coronary artery disease. After these tests, patients will be treated and followed according to routine care guidelines.
Primary purpose: DIAGNOSTIC

Brief summary: Yearly, 180 000 patients in the Netherlands are referred to a cardiologist with symptoms suspected of coronary artery disease (CAD). To assess this, multiple diagnostic tests are available. Non-invasive imaging tests, such as coronary CT-scan, are safe, relatively cheap and can effectively rule-out CAD. However, when CAD is present, coronary CT-scan cannot assess the restriction in blood flow caused by the stenosis. Cardiac angiography with invasive blood flow measurements is required to assess this restriction in blood flow. This is an invasive test, more expensive than CT and it is accompanied by certain risks.

Most patients in whom CAD is present do not need treatment, and would therefore benefit from non-invasive diagnostic tests. To reduce the number of unnecessary cardiac angiography with flow measurements, new imaging techniques have been developed. These techniques use CT- or angiographic images to calculate the restriction in coronary blood flow and determine the need for treatment. This study is designed to assess the safety and efficacy of these techniques when used as an addition to coronary CT-scan.

Subjects are eligible if their CT-scan indicates possibly significant CAD. To determine need for treatment of a subject's CAD, the investigators will randomize subjects in three arms. One arm consists of additional CT-derived calculation of coronary blood flow, one arm consists of angiography-derived calculation of coronary blood flow and one arm consists of standard care, coronary angiography and invasive coronary blood flow measurements. After these tests, subjects are treated and followed according to routine care guidelines. Additionally, subjects are requested to complete 5 questionnaires in a 12 month follow-up period.

The investigators expect that the total number of invasive cardiac angiographies with additional blood flow measurements can be reduced by half with the use of new imaging techniques. The investigators expect that this will lead to a reduction in healthcare costs, complications and a lower burden of diagnostic tests for patients. The investigators do not expect a difference in primary endpoints between the study groups.

Detailed description: Only a small proportion of the 180 000 patients that are referred to a cardiologist each year in the Netherlands with complaints of angina pectoris or shortness of breath suffer from coronary stenosis in such a degree that revascularisation is required. To identify these patients, multiple diagnostic tests are available. Simple non-interventional imaging tests, such as coronary CT-scan, are safe, relatively cheap and can effectively rule-out coronary artery disease. However, when coronary artery disease is present, coronary CT-scan cannot assess the restriction in blood flow caused by the stenosis. Cardiac angiography with invasive blood flow measurements is required to assess this restriction in blood flow. This is an invasive test, more expensive than CT and it is accompanied by certain risks.

In retrospect, many patients unnecessarily undergo cardiac angiography with, if deemed neccessary, flow measurements. These patients do not need treatment for coronary artery disease. To reduce the number of unnecessary cardiac angiography with flow measurements, new imaging techniques have been developed. These techniques use CT- or angiographic images to calculate the restriction in coronary blood flow and determine the need for treatment. These new imaging techniques have been tested extensively in observational studies. Currently, there is no consensus in the optimal diagnostic pathway resulting in major differences in strategies between hospitals. Moreover,data on cost-effectiveness is lacking.

This study is designed to assess the safety and efficacy of these techniques when used as an addition to coronary CT-scan. Our target population will be patients with complaints of angina pectoris or shortness of breath for which the patients will undergo coronary CT-scan. If the CT-scan shows one or more possibly flow-limiting stenoses, further diagnostic testing is required. These subjects are randomized in one of three possible arms. One arm will receive additional CT-derived calculation of coronary blood flow, one arm will receive angiography-derived calculation of coronary blood flow and one arm will receive standard care. Standard care consists of coronary angiography and invasive coronary blood flow measurements. The results of these tests determine the need for treatment of coronary artery disease. After these tests, subjects are treated according to routine care guidelines. Subjects are requested to complete 5 questionnaires in a 12 month follow-up period. The primary endpoint is a composite of MACE - all-cause mortality, aborted sudden cardiac death, myocardial infarction and unplanned hospitalization for chest pain leading to urgent revascularization during the 12-month follow-up period. Secondary endpoints consist of cost-effectiveness, the number of avoided invasive coronary angiographies and flow measurements and quality of life. The investigators will use hospital patient files and completed questionnaires to collect information about events during the follow-up period until the last included subject has completed their final questionnaire.

The investigators expect that the total number of invasive cardiac angiographies with additional blood flow measurements can be reduced by half with the use of new imaging techniques. The investigators expect that this will lead to a reduction in healthcare costs, complications and a lower burden of diagnostic tests for patients. The investigators do not expect a difference in primary endpoints between the study groups.

In addition to the randomised controlled trial, all eligible subjects whose coronary CT-scan does not show possibly significant coronary artery disease (CAD-RADS 0-2) are included in a patient registry. Because of absent or limited coronary artery disease, additional diagnostic testing is not needed in these patients. These subjects are requested to answer 5 questionnaires in a 12-month period, similar to the subjects included in the RCT-part of the trial. The outcome measures of this part of the trial are similar to those of the RCT. Our primary outcome is the occurrence of MACE-events, secondary outcomes are quality of life and patient satisfaction.

Eligibility criteria: Inclusion Criteria:

* The subject is willing and able to provide informed consent and adhere to study rules and regulations and follow-up
* The subject is clinically suspected of having (recurrent) angina pectoris or an equivalent and suspected coronary artery disease, based on symptoms and signs, history, clinical examination and baseline diagnostic testing (e.g. ECG recording and laboratory tests) as described in the 2019 ESC guideline on chronic coronary syndromes.
* The subject has had ≥64 multidetector row coronary CTA or will undergo coronary CTA as part of usual care deemed by the treating physician with ≥64 multidetector row coronary CTA.

Exclusion Criteria:

* The subject is suffering from unstable angina pectoris.
* The subject is suffering from decompensated congestive cardiac failure.
* The subject is suffering from a known non-ischemic cardiomyopathy.
* The subject has a history of PCI or CABG.
* The subject has had pacemaker or internal defibrillator leads implanted.
* The subject has a prosthetic heart valve.
* There is a severe language barrier.
* The subject participates in any other clinical trial that interferes with the current study.
* Clinical condition prohibiting subsequent interventional therapy as indicated by the results of the imaging procedures.
* The subject is or might be pregnant.
* The subject does not comply or is not able to comply to the imaging guidelines for the performance and acquisition of CCTA by the Society of Cardiac Computed Tomography (SCCT), including:

  * The subject is suffering from a cardiac rhythm other than sinus rhythm.
  * The subject is morbidly obese (Body Mass Index (BMI) \> 40).
  * The subject is not able to sustain a breath-hold for 25 seconds.
  * The subject is unable to remain in supine position for at least 30 minutes.
  * The subject has known allergies to or contra-indications to receiving an iodinated contrast agent. Contraindications to receiving an iodinated contrast agent: Glomerular Filtration Rate (GFR) \< 45 ml/min/1,73m2 and if the subject is diabetic or has at least two risk factors for developing contrast induced renal failure a GFR \< 60 ml/min/1,73m2.

Primary outcomes:
measure: Safety of non-invasive imaging techniques
timeFrame: 12 months
Secondary outcomes:
measure: Cost-effectiveness
timeFrame: 12 months
measure: Seattle Angina Pectoris Questionnaire
timeFrame: 12 months
measure: PHQ-9 Questionnaire
timeFrame: 12 months
measure: PROMIS-10 Questionnaire
timeFrame: 12 months
measure: Avoided coronary angiographies
timeFrame: 12 months
measure: Avoided invasive FFR-measurements
timeFrame: 12 months
Other outcomes:
Locations:
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
state: Brabant
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
state: Utrecht
city: Rotterdam
country: Netherlands
facility: Maasstad Hospital
state: Zuid-Holland
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: St. Antonius Ziekenhuis Nieuwegein
name: Martin J Swaans, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: UMC Utrecht
name: Tim Leiner, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: