Coronary Microvascular Function and CT Coronary Angiography (CorCTCA)

NCT03477890 | Active Not Recruiting DMC

• 1 other identifier: 17/CARD/25
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 3

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 \>=2.5 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.

Conditions

Angina, Stable; Angina Pectoris, Variant; Microvascular Angina

Outcome Measures

Primary Outcomes (1)

• Final diagnosis

  The between-group difference in the reclassification rate of the initial diagnosis based on CTCA vs. final diagnosis after the invasive procedure involving coronary function tests in a a major coronary artery using logistic regression, adjusted for baseline factors associated with the likelihood of reclassification of the initial diagnosis.

  Day 1

Secondary Outcomes (15)

• Occurrence of abnormal coronary function in a major epicardial coronary artery

  Day 1

• Presence of an obstructive or flow-limiting stenosis in a major coronary artery.

  Day 1

• Procedure-related serious adverse events

  Day 1

• Prevalence of endotypes

  Day 1

• Cardiovascular risk

  Day 1

Study Arms (2)

Intervention group (coronary function test results disclosed)

ACTIVE COMPARATOR

Coronary function tests are measured and disclosed to the clinician for re-evaluation of the initial diagnosis and treatment as compared with initial angiography. The intervention involves measurement of FFR, CFR, IMR and RRR in a major coronary artery followed by reactivity testing using incremental doses of acetylcholine (10-4 Molar (M), 10-5 M, 10-6 M) to assess endothelial function, bolus of ACh (10-4 M; 100 micrograms) for vasospasm, followed by glyceryl trinitrate (300 micrograms). FFR will be measured in all arteries with a diameter \>=2.5 mm and a stenosis 40% to 90% in severity. Endotypes are based on criteria for abnormal coronary vasodilator function, vasospasm and microvascular resistance. The endotypes (diagnostic strata) are: obstructive CAD, vasospastic angina, microvascular angina, mixed (ie both vasospastic and microvascular disorders), endothelial dysfunction (no angina), normal (non-cardiac). A diagnosis may be ruled-in or ruled-out based on the test results.

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 and protocol adherence is prospectively monitored.

Diagnostic Test: Stratified medicine involving a diagnostic intervention

Interventions

Stratified medicine involving a diagnostic intervention DIAGNOSTIC_TEST

Adjunctive tests of coronary artery lesion severity (fractional flow reserve) and function at the time of invasive coronary angiography. Diagnostic groups: stable coronary syndromes in patients with obstructive coronary artery disease (mis-classified by non-invasive CTCA) or no-obstructive coronary 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), Scottish Intercollegiate Guideline Network (SIGN), 2017).

Also known as: Adjunctive tests of coronary disease severity and function (disclosed)

Intervention group (coronary function test results disclosed)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptoms of angina or angina-equivalent informed by the Rose Angina questionnaire.
• Intermediate or no obstructive coronary disease i.e. no coronary stenosis \>70% in an artery \>2.5 mm, as revealed by CT coronary angiography.

You may not qualify if:

• A health problem that would explain the angina, e.g. anaemia, moderate-severe aortic stenosis, hypertrophic obstructive cardiomyopathy
• Obstructive disease evident in a coronary artery (diameter \>2.5 mm), i.e. \>50 - 70% circumferential plaque extending for ≥2 coronary segments, or a stenosis\>70% as revealed by CT coronary angiography
• Lack of informed consent.
• Flow-limiting coronary disease defined by a fractional flow reserve (FFR) ≤0.80 in an artery\>2.5 mm.

Sponsors & Collaborators

• NHS National Waiting Times Centre Board: lead
• University of Glasgow: collaborator
• British Heart Foundation: collaborator
• Chief Scientist Office of the Scottish Government: collaborator
• NHS Greater Clyde and Glasgow: collaborator

Study Sites (3)

Golden Jubilee National Hospital

Clydebank, Dunbartonshire, G814DY, United Kingdom

Location

Forth Valley Royal Hospital

Larbert, Forth Valley, FK5 4WR, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, Strathclyde, G4 0SF, United Kingdom

Location

Related Publications (17)

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• Sidik NP, McEntegart M, Roditi G, Ford TJ, McDermott M, Morrow A, Byrne J, Adams J, Hargreaves A, Oldroyd KG, Stobo D, Wu O, Messow CM, McConnachie A, Berry C. Rationale and design of the British Heart Foundation (BHF) Coronary Microvascular Function and CT Coronary Angiogram (CorCTCA) study. Am Heart J. 2020 Mar;221:48-59. doi: 10.1016/j.ahj.2019.11.015. Epub 2019 Dec 2.

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• Ford TJ, Yii E, Sidik N, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, McCartney P, Corcoran D, Collison D, Rush C, Stanley B, McConnachie A, Sattar N, Touyz RM, Oldroyd KG, Berry C. Ischemia and No Obstructive Coronary Artery Disease: Prevalence and Correlates of Coronary Vasomotion Disorders. Circ Cardiovasc Interv. 2019 Dec;12(12):e008126. doi: 10.1161/CIRCINTERVENTIONS.119.008126. Epub 2019 Dec 13.

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• Ford TJ, Stanley B, Sidik N, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, McCartney P, Corcoran D, Collison D, Rush C, Sattar N, McConnachie A, Touyz RM, Oldroyd KG, Berry C. 1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA). JACC Cardiovasc Interv. 2020 Jan 13;13(1):33-45. doi: 10.1016/j.jcin.2019.11.001. Epub 2019 Nov 11.

  PMID: 31709984 BACKGROUND

• Ford TJ, Stanley B, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, Sidik N, McCartney P, Corcoran D, Collison D, Rush C, McConnachie A, Touyz RM, Oldroyd KG, Berry C. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial. J Am Coll Cardiol. 2018 Dec 11;72(23 Pt A):2841-2855. doi: 10.1016/j.jacc.2018.09.006. Epub 2018 Sep 25.

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MeSH Terms

Conditions

Angina, Stable; Angina Pectoris, Variant; Microvascular Angina

Condition Hierarchy (Ancestors)

Angina Pectoris; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Angina, Unstable

Study Officials

• Katriona Brooksbank, PhD

  University of Glasgow

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants are randomised to a 'Disclosed group' (Intervention group) or a 'Not disclosed group' (Standard Care). In the standard care group, coronary function parameters are measured but the results are not disclosed to the attending clinician or the participant. Coronary function is measured in all participants.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Cardiology and Imaging

Model Details: Randomized, double-blind, parallel group, prospective

Study Record Dates

• First Submitted: October 6, 2017
• First Posted: March 27, 2018
• Study Start: August 31, 2017
• Primary Completion: December 20, 2023
• Study Completion (Estimated): August 31, 2033
• Last Updated: October 29, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: At study end

Locations

GB (3)