Angina, StableCorMicANCT03193294
CORonary MICrovascular Angina (CorMicA)
A study testing Stratified medicine involving a diagnostic intervention in people with Angina, Stable and Coronary Vasospasm, run by NHS National Waiting Times Centre Board at 2 sites in United Kingdom.
Trial summary
Angina is form of chest pain that is due to a lack of blood to the heart muscle. Angina is commonly triggered by stress and exertion, and is a common health problem worldwide. The diagnosis and treatment of angina is usually focused on detection of blockages in heart arteries, and relief of this problem with drugs… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Angina, Stable, Coronary Vasospasm, Coronary Circulation
- What is being tested?
- Stratified medicine involving a diagnostic intervention
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 151 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 7 Nov 2016to 6 Nov 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A clinically-indicated plan for invasive coronary angiography. Symptoms of angina or angina-equivalent (according to the Rose- and Seattle Angina questionnaires).
Who cannot join
- A non-coronary indication for invasive angiography e.g. valve disease During the angiogram: obstructive disease evident in a main coronary artery (diameter >2.5 mm), i.e. a coronary stenosis>50% or a fractional flow reserve (FFR) ≤0.80 Lack of informed consent.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Golden Jubilee National Hospital
Clydebank, Dunbartonshire, G814DY
Hairmyres Hospital
East Kilbride, Lanarkshire, G75 8RG
About this study
Official title: CORonary MICrovascular Angina (CorMicA): a Randomised, Controlled, Pilot Trial
Angina is form of chest pain that is due to a lack of blood to the heart muscle. Angina is commonly triggered by stress and exertion, and is a common health problem worldwide. The diagnosis and treatment of angina is usually focused on detection of blockages in heart arteries, and relief of this problem with drugs, stents or bypass surgery. However, about one third of all invasive angiograms that are performed in patients with angina do not reveal any blockages. Many of such patients may have symptoms due to narrowings in the very small micro vessels (too small to be seen on an angiogram). The purpose of this research is to undertake a 'proof-of-concept' clinical trial to gather information as to whether routine tests of small vessel function in the heart might help identify patients with a stable coronary syndrome due to a disorder of coronary function (vasospastic or microvascular angina), and appropriately rule out this problem in patients with normal test results. The diagnostic strategy enables stratification of patient sub-groups to optimized therapy (personalised medicine). Evidence of patient benefits in this study would support the plan for a larger study that would be designed to impact on healthcare costs and patient reported outcome measures (PROMS).
Read the detailed description
Background: Patients with a stable coronary syndromes include those with obstructive coronary artery disease (CAD) or ischaemia with no obstructive CAD (INOCA). Disorders of coronary vasomotion leading to microvascular and vasospastic angina are debilitating, prognostically important health problems. Use of coronary function tests with thresholds (normal/abnormal) that are linked to evidence-based treatment (start/stop) could be useful to diagnose (rule-in/rule-out) these conditions, but, evidence is lacking.
Design: (1) A proof-of-concept, randomised controlled stratified medicine trial of a clinical strategy informed by invasive tests of coronary function and linked guideline-based treatment decisions vs. standard care using angiography only in 150 patients; (2) A nested observational imaging sub-study using quantitative stress perfusion cardiac magnetic resonance (CMR). CONSORT guidelines will be followed.
Objectives: (1) To assess whether a diagnostic strategy involving tests of coronary function changes the diagnosis and treatment and improves health and economic outcomes; (2) To assess the diagnostic accuracy of novel MRI methods for abnormal perfusion due to microvascular disease.
Methods: Patients undergoing invasive coronary angiography for the investigation of known or suspected angina and who do not have either structural heart disease or a systemic health problem that would explain those symptoms will be invited to participate. Written informed consent is required for participation. Eligibility is further confirmed at the time of the coronary angiogram by exclusion of obstructive (>50% stenosis, fractional flow reserve <=0.80) coronary artery disease (CAD). After the angiogram, eligible participants will be randomised immediately in the catheter laboratory to test disclosure (intervention group) or measurement without disclosure (control group). Coronary function will be assessed using a diagnostic guidewire and intra-coronary infusions of acetylcholine (10-6M, 10-5M, -10-4M) and a bolus of glyceryl trinitrate (300 micrograms). The guidewire-derived parameters include fractional flow reserve (FFR), coronary flow reserve (CFR), index of microvascular resistance (IMR) and the resistance reserve ratio (RRR). Participants who are enrolled but not randomised will enter a follow-up registry. The endotypes (diagnostic strata) are: obstructive CAD, coronary vasospastic angina, microvascular angina, endothelial dysfunction (no angina), normal (non-cardiac, normal coronary function results, no angina). Thus, a diagnosis may be ruled-in or ruled-out based on the test results. Microvascular disease will be characterised as structural (abnormal IMR) and/or functional (abnormal CFR, RRR). Primary outcome: Between-group difference in Seattle Angina Questionnaire (SAQ) scores at 6 months; Secondary: Reclassification of the treatment decision; certainty of the diagnosis; health status (EQ-5D, Illness Perception, Treatment Satisfaction \& Patient Health questionnaires); angina medication and adherence; health economics; reference clinical decisions as evaluated by an independent expert panel of clinicians. Follow-up will continue in the longer term, including through electronic health record linkage.
Value: To our knowledge, the study is the first to assess the clinical value of invasive management guided by routine use of adjunctive tests of coronary function in appropriately selected patients. The study will provide new insights into disease mechanisms and provide pilot data to inform the rationale and design of a larger clinical trial. The CMR substudy will provide information on the diagnostic utility of quantitative non-invasive imaging methods in this patient population. Should our hypotheses be confirmed, the research will bring new knowledge with potential benefits to patients and healthcare providers.
- Conditions
- Angina, Stable, Coronary Vasospasm, Coronary Circulation, Coronary Syndrome, Microvascular Angina, Coronary Disease
- Being tested
- Stratified medicine involving a diagnostic intervention
- Medical subject headings
- Angina, Stable, Coronary Vasospasm, Angina, Unstable, Microvascular Angina, Coronary Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stratified medicine involving a diagnostic interventionDiagnostic test
Adjunctive tests of coronary artery function at the time of invasive coronary angiography. Diagnostic groups: stable coronary syndromes in patients with no-obstructive coronary artery disease including the following sub-groups (coronary artery vasospasm, microvascular spasm, impaired vasorelaxation due to (1) endothelial dysfunction and/or (2) non-endothelial dysfunction, or unaffected (normal test results). Medical management is linked to contemporary clinical guidelines for the management of patients with stable coronary artery disease (European Society of Cardiology (2013)).
| Study group | Role | What they receive |
|---|---|---|
| Intervention group (coronary function test results disclosed) | Active comparator | In the intervention group, coronary function tests are measured and disclosed to the attending clinician permitting re-evaluation of the initial diagnosis and treatment as compared with initial angiography-guided decisions. The intervention involves measurement of CFR, IMR and RRR in a target, major coronary artery followed by coronary reactivity testing using incremental doses of acetylcholine (10-4M, 10-5M, 10-6M) to assess endothelial function, bolus infusion of ACh (10-4M) for vasospasm provocation testing, followed by administration of a bolus dose (300 micrograms) of glyceryl trinitrate. Endotypes are identified based on established criteria for abnormalities in coronary vasodilator function, vasospasm and microvascular resistance. The endotypes (diagnostic strata) are: obstructive CAD, coronary artery spasm, microvascular angina, endothelial dysfunction (no angina), normal (non-cardiac). A diagnosis may be ruled-in or ruled-out based on the test results. Receives: Diagnostic Test: Stratified medicine involving a diagnostic intervention |
| Usual care group (coronary function results not disclosed) | Sham comparator | Coronary function tests are measured but not disclosed to the attending clinician or the participant. The same coronary function tests are undertaken as in the intervention group. Masking is achieved by obscuring the catheter laboratory monitors from the attending clinician and participant. The effectiveness of masking is prospectively monitored. Receives: Diagnostic Test: Stratified medicine involving a diagnostic intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Health status (Seattle Angina Score)
Health status and symptoms will be assessed at baseline and again at 6 months using the Seattle Angina Questionnaire. The primary outcome is the within-subject change in SAQ score at 6 months from baseline.
Measured: 6 months
Secondary outcomes (16)
Feasibility of the stratified medicine approach defined by protocol compliance as measured by deviations from the protocol.
Feasibility will be assessed in terms of enrolment rates and protocol compliance relating to enrolment, cross-over, integrity of blinding, adherence with therapy during follow-up, and compliance with follow up assessments
Measured: Through study completion, 3 years
Procedure-related serious adverse events
Safety as reflected by the occurrence of procedure-related serious adverse events
Measured: Day 1 (index coronary angiogram procedure)
Prevalence of endotypes
Diagnosis of endotypes (disease strata): obstructive CAD, coronary vasospastic angina, microvascular angina, endothelial dysfunction (no angina), normal (non-cardiac, normal coronary function results, no angina).
Measured: Day 1
Diagnostic utility of the diagnostic intervention
Impact of disclosure of the coronary function test results on the diagnosis and certainty of the diagnosis (diagnostic utility)
Measured: Day 1
Clinical utility of the stratified approach
Impact of disclosure of the coronary function test results on medical decisions (including treatment and investigations), and to compare these decisions against a medical decisions formed by an independent panel of experts (reference dataset)
Measured: Day 1
Cardiovascular risk factors
Assess the relationships between cardiovascular risk factors, reflected by validated risk scores (e.g. ASSIGN, JBS3), and parameters of coronary function, in medically managed patients.
Measured: Day 1
Anxiety and depression
Assess the participants' self-reported levels of anxiety and depression using the Patient Health Questionnaire-4 (PHQ-4)
Measured: Through study completion, 3 years
Treatment satisfaction
Assess the participants' self-reported levels of treatment satisfaction using the Treatment Satisfaction Questionnaire for Medication (TSQM)
Measured: Through study completion, 3 years
Illness perception
Assess the participants' perception of their illness using the brief Illness Perception Questionnaire
Measured: Through study completion, 3 years
Health status EQ5D
Assess the participants' general health status and self reported quality of life using the EQ5D questionnaire.
Measured: Through study completion, 3 years
Health status (Seattle Angina Score)
Health status and symptoms will be assessed at baseline and again at 6 months, 12 months and close-out using the Seattle Angina Questionnaire. The secondary outcome is the within-subject change in SAQ score over time.
Measured: Through study completion, 3 years
Biomarkers
Assess associations between circulating molecules that are implicated in the pathophysiology of disorders of coronary function.
Measured: 36 months
Health economics
Assess resource utilisation including primary and secondary care costs for tests, procedures and out-patient visits, and medicines, between the randomised groups
Measured: 36 months
Myocardial perfusion
Assess the diagnostic accuracy of stress perfusion magnetic resonance imaging for identification of endotypes based on reference tests of coronary function.
Measured: 42 days
Incidental findings
Detection of clinically significant (actionable) incidental findings using magnetic resonance imaging. The incidental findings may be cardiac or non-cardiac.
Measured: 42 days
Myocardial tissue characterisation
Detection of myocardial pathology using multiparametric CMR
Measured: 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2017
- Study start7 Nov 2016
- Primary completion31 Jul 2019
- Study completion6 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Angina, StableStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind, parallel group, prospective
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 151 participants (actual)
Sponsor and investigators
- Lead sponsor
- NHS National Waiting Times Centre Board
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation
- Responsible party
- Principal investigator, Colin Berry, NHS National Waiting Times Centre Board
- Investigators
- Katriona Brooksbank, PhD, Study director, University of Glasgow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03193294
- Sponsor's protocol ID
- 16CARD25
- Acronym
- CorMicA
- Status last verified
- Oct 2024
- First submitted
- 13 Jun 2017
- Last updated
- 29 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data access may be possible pending Sponsor approval
Publications
Ford TJ, Ong P, Sechtem U, Beltrame J, Camici PG, Crea F, Kaski JC, Bairey Merz CN, Pepine CJ, Shimokawa H, Berry C; COVADIS Study Group. Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease: Why, How, and When. JACC Cardiovasc Interv. 2020 Aug 24;13(16):1847-1864. doi: 10.1016/j.jcin.2020.05.052.
PubMed 32819476Ford TJ, Corcoran D, Sidik N, Oldroyd KG, Rocchiccioli P, McEntegart M, Berry C. MINOCA: Requirement for Definitive Diagnostic Work-Up. Heart Lung Circ. 2019 Feb;28(2):e4-e6. doi: 10.1016/j.hlc.2018.04.001. No abstract available.
PubMed 30654950Collison D, Copt S, Mizukami T, Collet C, McLaren R, Didagelos M, Aetesam-Ur-Rahman M, McCartney P, Ford TJ, Lindsay M, Shaukat A, Rocchiccioli P, Brogan R, Watkins S, McEntegart M, Good R, Robertson K, O'Boyle P, Davie A, Khan A, Hood S, Eteiba H, Berry C, Oldroyd KG. Angina After Percutaneous Coronary Intervention: Patient and Procedural Predictors. Circ Cardiovasc Interv. 2023 Apr;16(4):e012511. doi: 10.1161/CIRCINTERVENTIONS.122.012511. Epub 2023 Mar 28.
PubMed 36974680Rush CJ, Berry C, Oldroyd KG, Rocchiccioli JP, Lindsay MM, Touyz RM, Murphy CL, Ford TJ, Sidik N, McEntegart MB, Lang NN, Jhund PS, Campbell RT, McMurray JJV, Petrie MC. Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction. JAMA Cardiol. 2021 Oct 1;6(10):1130-1143. doi: 10.1001/jamacardio.2021.1825.
PubMed 34160566Kunadian V, Chieffo A, Camici PG, Berry C, Escaned J, Maas AHEM, Prescott E, Karam N, Appelman Y, Fraccaro C, Louise Buchanan G, Manzo-Silberman S, Al-Lamee R, Regar E, Lansky A, Abbott JD, Badimon L, Duncker DJ, Mehran R, Capodanno D, Baumbach A. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. Eur Heart J. 2020 Oct 1;41(37):3504-3520. doi: 10.1093/eurheartj/ehaa503.
PubMed 32626906Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S; ESC Scientific Document Group. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024 Sep 29;45(36):3415-3537. doi: 10.1093/eurheartj/ehae177. No abstract available.
PubMed 39210710Cannon RO 3rd, Leon MB, Watson RM, Rosing DR, Epstein SE. Chest pain and "normal" coronary arteries--role of small coronary arteries. Am J Cardiol. 1985 Jan 25;55(3):50B-60B. doi: 10.1016/0002-9149(85)90613-7.
PubMed 3969858Cannon RO 3rd, Bonow RO, Bacharach SL, Green MV, Rosing DR, Leon MB, Watson RM, Epstein SE. Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve. Circulation. 1985 Feb;71(2):218-26. doi: 10.1161/01.cir.71.2.218.
PubMed 3965167Sax FL, Cannon RO 3rd, Hanson C, Epstein SE. Impaired forearm vasodilator reserve in patients with microvascular angina. Evidence of a generalized disorder of vascular function? N Engl J Med. 1987 Nov 26;317(22):1366-70. doi: 10.1056/NEJM198711263172202.
PubMed 3683470Kaski JC, Elliott PM, Salomone O, Dickinson K, Gordon D, Hann C, Holt DW. Concentration of circulating plasma endothelin in patients with angina and normal coronary angiograms. Br Heart J. 1995 Dec;74(6):620-4. doi: 10.1136/hrt.74.6.620.
PubMed 8541166Elliott PM, Krzyzowska-Dickinson K, Calvino R, Hann C, Kaski JC. Effect of oral aminophylline in patients with angina and normal coronary arteriograms (cardiac syndrome X). Heart. 1997 Jun;77(6):523-6. doi: 10.1136/hrt.77.6.523.
PubMed 9227295Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Bairey Merz CN; Coronary Vasomotion Disorders International Study Group (COVADIS). The Who, What, Why, When, How and Where of Vasospastic Angina. Circ J. 2016;80(2):289-98. doi: 10.1253/circj.CJ-15-1202. Epub 2015 Dec 18.
PubMed 26686994Williams MC, Hunter A, Shah A, Assi V, Lewis S, Mangion K, Berry C, Boon NA, Clark E, Flather M, Forbes J, McLean S, Roditi G, van Beek EJ, Timmis AD, Newby DE; Scottish COmputed Tomography of the HEART (SCOT-HEART) Trial Investigators. Symptoms and quality of life in patients with suspected angina undergoing CT coronary angiography: a randomised controlled trial. Heart. 2017 Jul;103(13):995-1001. doi: 10.1136/heartjnl-2016-310129. Epub 2017 Feb 28.
PubMed 28246175Ford TJ, Corcoran D, Berry C. Coronary artery disease: physiology and prognosis. Eur Heart J. 2017 Jul 1;38(25):1990-1992. doi: 10.1093/eurheartj/ehx226. No abstract available.
PubMed 28549103Ford TJ, Berry C. Angina: contemporary diagnosis and management. Heart. 2020 Mar;106(5):387-398. doi: 10.1136/heartjnl-2018-314661. Epub 2020 Feb 12. No abstract available.
PubMed 32054665
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CORonary MICrovascular Angina (CorMicA): a Randomised, Controlled, Pilot Trial
- ClinicalTrials.gov ID
- NCT03193294
- Acronym / sponsor ID
- CorMicA / 16CARD25
- Conditions
- Angina, Stable, Coronary Vasospasm, Coronary Circulation, Coronary Syndrome, Microvascular Angina, Coronary Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 151 participants (actual)
- Lead sponsor
- NHS National Waiting Times Centre BoardUniversity, hospital or other
- Collaborators
- British Heart Foundation
- Study start
- 7 Nov 2016 (actual)
- Primary completion
- 31 Jul 2019 (actual)
- Study completion
- 6 Nov 2019 (actual)
- First posted
- 20 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Angina is form of chest pain that is due to a lack of blood to the heart muscle. Angina is commonly triggered by stress and exertion, and is a common health problem worldwide. The diagnosis and treatment of angina is usually focused on detection of blockages in heart arteries, and relief of this problem with drugs, stents or bypass surgery. However, about one third of all invasive angiograms that are performed in patients with angina do not reveal any blockages. Many of such patients may have symptoms due to narrowings in the very small micro vessels (too small to be seen on an angiogram). The purpose of this research is to undertake a 'proof-of-concept' clinical trial to gather information as to whether routine tests of small vessel function in the heart might help identify patients with a stable coronary syndrome due to a disorder of coronary function (vasospastic or microvascular angina), and appropriately rule out this problem in patients with normal test results. The diagnostic strategy enables stratification of patient sub-groups to optimized therapy (personalised medicine). Evidence of patient benefits in this study would support the plan for a larger study that would be designed to impact on healthcare costs and patient reported outcome measures (PROMS).
Detailed description
Background: Patients with a stable coronary syndromes include those with obstructive coronary artery disease (CAD) or ischaemia with no obstructive CAD (INOCA). Disorders of coronary vasomotion leading to microvascular and vasospastic angina are debilitating, prognostically important health problems. Use of coronary function tests with thresholds (normal/abnormal) that are linked to evidence-based treatment (start/stop) could be useful to diagnose (rule-in/rule-out) these conditions, but, evidence is lacking.
Design: (1) A proof-of-concept, randomised controlled stratified medicine trial of a clinical strategy informed by invasive tests of coronary function and linked guideline-based treatment decisions vs. standard care using angiography only in 150 patients; (2) A nested observational imaging sub-study using quantitative stress perfusion cardiac magnetic resonance (CMR). CONSORT guidelines will be followed.
Objectives: (1) To assess whether a diagnostic strategy involving tests of coronary function changes the diagnosis and treatment and improves health and economic outcomes; (2) To assess the diagnostic accuracy of novel MRI methods for abnormal perfusion due to microvascular disease.
Methods: Patients undergoing invasive coronary angiography for the investigation of known or suspected angina and who do not have either structural heart disease or a systemic health problem that would explain those symptoms will be invited to participate. Written informed consent is required for participation. Eligibility is further confirmed at the time of the coronary angiogram by exclusion of obstructive (>50% stenosis, fractional flow reserve <=0.80) coronary artery disease (CAD). After the angiogram, eligible participants will be randomised immediately in the catheter laboratory to test disclosure (intervention group) or measurement without disclosure (control group). Coronary function will be assessed using a diagnostic guidewire and intra-coronary infusions of acetylcholine (10-6M, 10-5M, -10-4M) and a bolus of glyceryl trinitrate (300 micrograms). The guidewire-derived parameters include fractional flow reserve (FFR), coronary flow reserve (CFR), index of microvascular resistance (IMR) and the resistance reserve ratio (RRR). Participants who are enrolled but not randomised will enter a follow-up registry. The endotypes (diagnostic strata) are: obstructive CAD, coronary vasospastic angina, microvascular angina, endothelial dysfunction (no angina), normal (non-cardiac, normal coronary function results, no angina). Thus, a diagnosis may be ruled-in or ruled-out based on the test results. Microvascular disease will be characterised as structural (abnormal IMR) and/or functional (abnormal CFR, RRR). Primary outcome: Between-group difference in Seattle Angina Questionnaire (SAQ) scores at 6 months; Secondary: Reclassification of the treatment decision; certainty of the diagnosis; health status (EQ-5D, Illness Perception, Treatment Satisfaction \& Patient Health questionnaires); angina medication and adherence; health economics; reference clinical decisions as evaluated by an independent expert panel of clinicians. Follow-up will continue in the longer term, including through electronic health record linkage.
Value: To our knowledge, the study is the first to assess the clinical value of invasive management guided by routine use of adjunctive tests of coronary function in appropriately selected patients. The study will provide new insights into disease mechanisms and provide pilot data to inform the rationale and design of a larger clinical trial. The CMR substudy will provide information on the diagnostic utility of quantitative non-invasive imaging methods in this patient population. Should our hypotheses be confirmed, the research will bring new knowledge with potential benefits to patients and healthcare providers.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double-blind, parallel group, prospective
| Arm | Type | Receives |
|---|---|---|
| Intervention group (coronary function test results disclosed) | Active comparator | Diagnostic Test: Stratified medicine involving a diagnostic interventionIn the intervention group, coronary function tests are measured and disclosed to the attending clinician permitting re-evaluation of the initial diagnosis and treatment as compared with initial angiography-guided decisions. The intervention involves measurement of CFR, IMR and RRR in a target, major coronary artery followed by coronary reactivity testing using incremental doses of acetylcholine (10-4M, 10-5M, 10-6M) to assess endothelial function, bolus infusion of ACh (10-4M) for vasospasm provocation testing, followed by administration of a bolus dose (300 micrograms) of glyceryl trinitrate. Endotypes are identified based on established criteria for abnormalities in coronary vasodilator function, vasospasm and microvascular resistance. The endotypes (diagnostic strata) are: obstructive CAD, coronary artery spasm, microvascular angina, endothelial dysfunction (no angina), normal (non-cardiac). A diagnosis may be ruled-in or ruled-out based on the test results. |
| Usual care group (coronary function results not disclosed) | Sham comparator | Diagnostic Test: Stratified medicine involving a diagnostic interventionCoronary function tests are measured but not disclosed to the attending clinician or the participant. The same coronary function tests are undertaken as in the intervention group. Masking is achieved by obscuring the catheter laboratory monitors from the attending clinician and participant. The effectiveness of masking is prospectively monitored. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- A clinically-indicated plan for invasive coronary angiography. Symptoms of angina or angina-equivalent (according to the Rose- and Seattle Angina questionnaires).
Key exclusion criteria (1 listed)
- A non-coronary indication for invasive angiography e.g. valve disease During the angiogram: obstructive disease evident in a main coronary artery (diameter >2.5 mm), i.e. a coronary stenosis>50% or a fractional flow reserve (FFR) ≤0.80 Lack of informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stratified medicine involving a diagnostic interventionAdjunctive tests of coronary artery function at the time of invasive coronary angiography. Diagnostic groups: stable coronary syndromes in patients with no-obstructive coronary artery disease including the following sub-groups (coronary artery vasospasm, microvascular spasm, impaired vasorelaxation due to (1) endothelial dysfunction and/or (2) non-endothelial dysfunction, or unaffected (normal test results). Medical management is linked to contemporary clinical guidelines for the management of patients with stable coronary artery disease (European Society of Cardiology (2013)). | Diagnostic test | Intervention group (coronary function test results disclosed), Usual care group (coronary function results not disclosed) |
Primary outcome
Health status (Seattle Angina Score)
Time frame: 6 months
Health status and symptoms will be assessed at baseline and again at 6 months using the Seattle Angina Questionnaire. The primary outcome is the within-subject change in SAQ score at 6 months from baseline.
16 secondary outcomes
Feasibility of the stratified medicine approach defined by protocol compliance as measured by deviations from the protocol.
Time frame: Through study completion, 3 years
Procedure-related serious adverse events
Time frame: Day 1 (index coronary angiogram procedure)
Prevalence of endotypes
Time frame: Day 1
Diagnostic utility of the diagnostic intervention
Time frame: Day 1
Clinical utility of the stratified approach
Time frame: Day 1
Cardiovascular risk factors
Time frame: Day 1
Anxiety and depression
Time frame: Through study completion, 3 years
Treatment satisfaction
Time frame: Through study completion, 3 years
Illness perception
Time frame: Through study completion, 3 years
Health status EQ5D
Time frame: Through study completion, 3 years
Health status (Seattle Angina Score)
Time frame: Through study completion, 3 years
Biomarkers
Time frame: 36 months
Health economics
Time frame: 36 months
Myocardial perfusion
Time frame: 42 days
Incidental findings
Time frame: 42 days
Myocardial tissue characterisation
Time frame: 42 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2024.
- Background: PubMed 32819476Ford TJ, Ong P, Sechtem U, Beltrame J, Camici PG, Crea F, Kaski JC, Bairey Merz CN, Pepine CJ, Shimokawa H, Berry C; COVADIS Study Group. Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease: Why, How, and When. JACC Cardiovasc Interv. 2020 Aug 24;13(16):1847-1864. doi: 10.1016/j.jcin.2020.05.052.
- Background: PubMed 30654950Ford TJ, Corcoran D, Sidik N, Oldroyd KG, Rocchiccioli P, McEntegart M, Berry C. MINOCA: Requirement for Definitive Diagnostic Work-Up. Heart Lung Circ. 2019 Feb;28(2):e4-e6. doi: 10.1016/j.hlc.2018.04.001. No abstract available.
- Background: PubMed 36974680Collison D, Copt S, Mizukami T, Collet C, McLaren R, Didagelos M, Aetesam-Ur-Rahman M, McCartney P, Ford TJ, Lindsay M, Shaukat A, Rocchiccioli P, Brogan R, Watkins S, McEntegart M, Good R, Robertson K, O'Boyle P, Davie A, Khan A, Hood S, Eteiba H, Berry C, Oldroyd KG. Angina After Percutaneous Coronary Intervention: Patient and Procedural Predictors. Circ Cardiovasc Interv. 2023 Apr;16(4):e012511. doi: 10.1161/CIRCINTERVENTIONS.122.012511. Epub 2023 Mar 28.
- Background: PubMed 34160566Rush CJ, Berry C, Oldroyd KG, Rocchiccioli JP, Lindsay MM, Touyz RM, Murphy CL, Ford TJ, Sidik N, McEntegart MB, Lang NN, Jhund PS, Campbell RT, McMurray JJV, Petrie MC. Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction. JAMA Cardiol. 2021 Oct 1;6(10):1130-1143. doi: 10.1001/jamacardio.2021.1825.
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- Cardiology and Imaging Group, University of GlasgowLink provided by the sponsor.
- Cardiology Department, Golden Jubilee National HospitalLink provided by the sponsor.
- British Heart Foundation Centre of Research Excellence, University of GlasgowLink provided by the sponsor.
- British Heart FoundationLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Data access may be possible pending Sponsor approval
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katriona Brooksbank, PhD study director
University of Glasgow
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stratified medicine involving a diagnostic intervention in people with Angina, Stable and Coronary Vasospasm, run by NHS National Waiting Times Centre Board at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Health status (Seattle Angina Score) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03193294, which also lists 23 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2024.