Ignite Creation Date:
2024-05-06 @ 11:15 AM
Last Modification Date:
2024-10-26 @ 12:42 PM
Study NCT ID:
NCT03477890
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2022-01-10
First Post:
2017-10-06
Brief Title:
Coronary Microvascular Function and CT Coronary Angiography CorCTCA
Sponsor:
NHS National Waiting Times Centre Board
Organization:
NHS National Waiting Times Centre Board
Study Overview
Official Title:
Angina in Patients Without Obstructive Coronary Disease as Revealed by CT Coronary Angiography Cor-CTCA an Observational Cohort Study Involving Coronary Function Tests and a Nested Randomised Trial
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2022-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CorCTCA
Brief Summary:
Angina in patients without obstructive coronary artery disease CAD is a clinical conundrum and patient management is heterogeneous Hypothesis Abnormal coronary function is common and clinically relevant in this population Design An observational cohort study and nested randomised controlled diagnostic strategy trial Methods 250 patients with known or suspected angina informed by validated questionnaires but without obstructive CAD 70 stenosis in an artery 25 mm or structural heart disease as revealed by CT coronary angiography CTCA will be invited to undergo coronary function testing FFR CFR IMR intra-coronary ACh during invasive angiography Patients will be randomised following angiography but before testing coronary function to disclosure of the coronary function test results or not Treatment decisions by the attending cardiologist will be recorded before and after disclosure of results Outcomes Primary The between-group difference in the reclassification rate of the initial diagnosis using logistic regression adjusted for baseline factors associated with the likelihood of reclassification of the initial diagnosis Secondary Prevalence of microvascular or vasospastic angina health status reflected by the EuroQol group 5-Dimensions EQ-5D Seattle Angina Questionnaire Illness perception treatment satisfaction questionnaires and functional status questionnaires angina medication and adherence Value This research will provide new insights into the conundrum of angina in patients without obstructive CAD or structural heart disease
Detailed Description:
According to information provided by the British Heart Foundation there are approximately 23 million men and women living with angina in the United Kingdom UK In 2014 there were 247363 coronary angiograms performed mostly for the investigation of known or suspected angina but only about half of the patients have obstructive coronary artery disease CAD identified by the angiogram Considering CT coronary angiography CTCA 1 in 4 patients referred to the Chest Pain Clinic with chest pain of suspected cardiac origin have obstructive CAD identified by the CTCA scan The explanation for the causes of the chest pain are often unclear which can be frustrating to patients and clinicians Small vessel disease ie microvascular or vasospastic angina may be one explanation
Anatomical imaging of the coronary arteries non-invasively by CTCA or invasively is an insensitive approach for the assessment of coronary function and even visual assessment of the angiogram for obstructive CAD by invasive angiography or CTCA may sometimes lead to mis-diagnosis and sub-optimal outcomes Novel adjunctive tests of coronary function may have incremental diagnostic value to further inform medical decisions Taken together the literature and practice guidelines suggest a clinical problem of unmet need with the potential for benefits to patients and healthcare providers if the diagnostic management can be improved Our proposal addresses the evidence gap by exploiting advances in diagnostic tests to gather information on the prevalence of microvascular and vasospastic disorders in patients with angina in whom obstructive CAD has been ruled out By implementing a diagnostic management strategy in the context of a randomised blinded controlled trial the investigators aim to determine whether use of coronary function tests in relevant patients might be beneficial
Angina in patients without obstructive CAD and insights from contemporary clinical trials The Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 FAME-2 Scottish COmputed Tomography of the HEART SCOT-HEART Prospective Multicenter Imaging Study for Evaluation of Chest Pain PROMISE and Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 CE-MARC 2 2 trials focused on the diagnosis and treatment of angina due to obstructive CAD Paradoxically the findings in these trials have diagnosed considerable numbers of patients with angina without obstructive CAD In FAME-2 of 1220 patients with stable CAD 332 27 had non-flow limiting FFR080 CAD The distribution of the Canadian Cardiovascular Society angina classes was similar between the randomised patients and those in the registry p064 as was the prevalence of silent ischaemia 16 p096 The registry patients were treated with medical therapy and the MACE rate was 9 at 2 years
In SCOT-HEART of 4146 patients with suspected angina assessed at the Chest Pain Clinic 2450 59 had confirmed angina typical or atypical yet considering the prevalence of obstructive CAD as revealed by CTCA 70 stenosis in 1 major branches or 50 in the left main stem just 25 had obstructive CAD In the PROMISE trial 10003 participants n8939 894 with typical or atypical angina were randomised to a strategy of initial anatomical testing with CTCA or to a strategy of functional testing exercise ECG or stress imaging Using similar diagnostic criteria as in SCOT-HEART only 517 107 of the 4996 participants in the CTCA group had a positive result No further data were provided to explain the aetiology of the angina in the patients without obstructive CAD
Most recently the CE-MARC 2 trial compared diagnostic strategies in patients referred to the Chest Pain Clinic with a pre-test likelihood of CAD of 10 to 90 All n1202 of the participants had a history of angina with 401 334 having typical angina Only a minority of participants had a positive non-invasive test 124 in the CMR group 182 in the myocardial perfusion scintigraphy MPS group and 134 in the NICE Guideline group Invasive coronary angiography was performed within 12 months of randomisation in 265 22 patients The primary outcome of unnecessary angiography defined as an FFR08 or quantitative coronary analysis showing no stenosis 70 in 1 view or 50 in 2 orthogonal views in all coronary vessels 25 mm diameter occurred in 139 subjects 12 75 in the CMR group 71 in the MPS group and 288 of participants in the NICE guidelines group CEMARC 2 was a pragmatic trial and since invasive angiography was not performed in all of the subjects the causes of the angina in patients with negative non-invasive imaging tests were unclear Finally the ISCHEMIA trial investigators have observed that some of the participants enrolled with moderate-severe myocardial ischemia on stress testing left ventricular LV mass do not have obstructive CAD The Changes in Ischemia and Angina over One year among ISCHEMIA trial screen failures with no obstructive coronary artery disease on coronary CT angiography CIAO-ISCHEMIA study has been instigated to investigate these patients in greater detail
In the SCOT-HEART trial symptoms and quality of life assessed at baseline and 6 months improved less in patients assigned to the CTCA-guided strategy as compared to standard care This analysis refuted the hypothesis that symptoms and quality of life would improve with a CTCA-guided strategy and it conflicts with the NICE-95 guideline recommendations Patients in the CTCA group with a change in diagnosis confirming obstructive CAD or excluding CAD had the greatest improvement in symptoms By contrast patients with non-obstructive CAD had the least improvement in symptoms There could be several reasons to explain this finding Firstly patient satisfaction may be greater with a definitive diagnosis and treatment plan ie 1 normal coronaries - stop treatment 2 obstructive CAD - percutaneous coronary intervention PCI or coronary artery bypass surgery CABG while a result of intermediate CAD with no change in treatment may result in lower patient satisfaction Secondly a false negative CTCA result may have occurred in some patients with flow limiting CAD since objective assessments of flow limiting CAD andor ischaemia were not performed Finally some patients with non-obstructive CAD may have had microvascular disease Since clinicians may have stopped angina treatment in patients without obstructive CAD the symptoms of patients who had microvascular angina and a negative CTCA scan may have deteriorated
The design of our study includes a multicentre observational study involving novel diagnostic tests of coronary function in order to provide information on the prevalence of microvascular andor vasospastic disease in patients with angina but non obstructive CAD as revealed by CTCA The CTCA protocol will be undertaken according optimal standards ie heart rate control with beta-blocker medication administration of sublingual nitrate before the CTCA scan etc The clinical relevance of additional tests of coronary function will be assessed through a nested randomised strategy trial of management diagnosis and treatment guided by the coronary function test results versus standard care guided by angiography The possibility of occasional CAD misclassification by CTCA ie false negative obstructive CAD will also be assessed Follow-up will include assessments of health well-being and treatment satisfaction The wider adoption of anatomical imaging with CTCA as a first-line diagnostic test for the assessment of stable chest pain NICE-95 guideline update November 2016 supports the rationale for this research
Anatomical imaging of the coronary arteries non-invasively by CTCA or invasively is an insensitive approach for the assessment of coronary function and even visual assessment of the angiogram for obstructive CAD by invasive angiography or CTCA may sometimes lead to mis-diagnosis and sub-optimal outcomes Novel adjunctive tests of coronary function may have incremental diagnostic value to further inform medical decisions Taken together the literature and practice guidelines suggest a clinical problem of unmet need with the potential for benefits to patients and healthcare providers if the diagnostic management can be improved Our proposal addresses the evidence gap by exploiting advances in diagnostic tests to gather information on the prevalence of microvascular and vasospastic disorders in patients with angina in whom obstructive CAD has been ruled out By implementing a diagnostic management strategy in the context of a randomised blinded controlled trial the investigators aim to determine whether use of coronary function tests in relevant patients might be beneficial
Angina in patients without obstructive CAD and insights from contemporary clinical trials The Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 FAME-2 Scottish COmputed Tomography of the HEART SCOT-HEART Prospective Multicenter Imaging Study for Evaluation of Chest Pain PROMISE and Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 CE-MARC 2 2 trials focused on the diagnosis and treatment of angina due to obstructive CAD Paradoxically the findings in these trials have diagnosed considerable numbers of patients with angina without obstructive CAD In FAME-2 of 1220 patients with stable CAD 332 27 had non-flow limiting FFR080 CAD The distribution of the Canadian Cardiovascular Society angina classes was similar between the randomised patients and those in the registry p064 as was the prevalence of silent ischaemia 16 p096 The registry patients were treated with medical therapy and the MACE rate was 9 at 2 years
In SCOT-HEART of 4146 patients with suspected angina assessed at the Chest Pain Clinic 2450 59 had confirmed angina typical or atypical yet considering the prevalence of obstructive CAD as revealed by CTCA 70 stenosis in 1 major branches or 50 in the left main stem just 25 had obstructive CAD In the PROMISE trial 10003 participants n8939 894 with typical or atypical angina were randomised to a strategy of initial anatomical testing with CTCA or to a strategy of functional testing exercise ECG or stress imaging Using similar diagnostic criteria as in SCOT-HEART only 517 107 of the 4996 participants in the CTCA group had a positive result No further data were provided to explain the aetiology of the angina in the patients without obstructive CAD
Most recently the CE-MARC 2 trial compared diagnostic strategies in patients referred to the Chest Pain Clinic with a pre-test likelihood of CAD of 10 to 90 All n1202 of the participants had a history of angina with 401 334 having typical angina Only a minority of participants had a positive non-invasive test 124 in the CMR group 182 in the myocardial perfusion scintigraphy MPS group and 134 in the NICE Guideline group Invasive coronary angiography was performed within 12 months of randomisation in 265 22 patients The primary outcome of unnecessary angiography defined as an FFR08 or quantitative coronary analysis showing no stenosis 70 in 1 view or 50 in 2 orthogonal views in all coronary vessels 25 mm diameter occurred in 139 subjects 12 75 in the CMR group 71 in the MPS group and 288 of participants in the NICE guidelines group CEMARC 2 was a pragmatic trial and since invasive angiography was not performed in all of the subjects the causes of the angina in patients with negative non-invasive imaging tests were unclear Finally the ISCHEMIA trial investigators have observed that some of the participants enrolled with moderate-severe myocardial ischemia on stress testing left ventricular LV mass do not have obstructive CAD The Changes in Ischemia and Angina over One year among ISCHEMIA trial screen failures with no obstructive coronary artery disease on coronary CT angiography CIAO-ISCHEMIA study has been instigated to investigate these patients in greater detail
In the SCOT-HEART trial symptoms and quality of life assessed at baseline and 6 months improved less in patients assigned to the CTCA-guided strategy as compared to standard care This analysis refuted the hypothesis that symptoms and quality of life would improve with a CTCA-guided strategy and it conflicts with the NICE-95 guideline recommendations Patients in the CTCA group with a change in diagnosis confirming obstructive CAD or excluding CAD had the greatest improvement in symptoms By contrast patients with non-obstructive CAD had the least improvement in symptoms There could be several reasons to explain this finding Firstly patient satisfaction may be greater with a definitive diagnosis and treatment plan ie 1 normal coronaries - stop treatment 2 obstructive CAD - percutaneous coronary intervention PCI or coronary artery bypass surgery CABG while a result of intermediate CAD with no change in treatment may result in lower patient satisfaction Secondly a false negative CTCA result may have occurred in some patients with flow limiting CAD since objective assessments of flow limiting CAD andor ischaemia were not performed Finally some patients with non-obstructive CAD may have had microvascular disease Since clinicians may have stopped angina treatment in patients without obstructive CAD the symptoms of patients who had microvascular angina and a negative CTCA scan may have deteriorated
The design of our study includes a multicentre observational study involving novel diagnostic tests of coronary function in order to provide information on the prevalence of microvascular andor vasospastic disease in patients with angina but non obstructive CAD as revealed by CTCA The CTCA protocol will be undertaken according optimal standards ie heart rate control with beta-blocker medication administration of sublingual nitrate before the CTCA scan etc The clinical relevance of additional tests of coronary function will be assessed through a nested randomised strategy trial of management diagnosis and treatment guided by the coronary function test results versus standard care guided by angiography The possibility of occasional CAD misclassification by CTCA ie false negative obstructive CAD will also be assessed Follow-up will include assessments of health well-being and treatment satisfaction The wider adoption of anatomical imaging with CTCA as a first-line diagnostic test for the assessment of stable chest pain NICE-95 guideline update November 2016 supports the rationale for this research
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None