ClinicalTrials.gov
ClinicalTrials.gov Menu

CORonary MICrovascular Angina (CorMicA) (CorMicA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03193294
Recruitment Status : Active, not recruiting
First Posted : June 20, 2017
Last Update Posted : March 13, 2018
Sponsor:
Collaborator:
British Heart Foundation
Information provided by (Responsible Party):
Colin Berry, NHS National Waiting Times Centre Board

Brief 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, 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).

Condition or disease Intervention/treatment Phase
Angina, Stable Coronary Vasospasm Coronary Circulation Coronary Syndrome Microvascular Angina Coronary Disease Diagnostic Test: Stratified medicine involving a diagnostic intervention Not Applicable

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, double-blind, parallel group, prospective
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Diagnostic
Official Title: CORonary MICrovascular Angina (CorMicA): a Randomised, Controlled, Pilot Trial
Study Start Date : November 7, 2016
Estimated Primary Completion Date : July 31, 2019
Estimated Study Completion Date : November 6, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Angina

Arm Intervention/treatment
Active Comparator: Intervention group (coronary function test results disclosed)
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.
Diagnostic Test: Stratified medicine involving a diagnostic intervention
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)).

Sham Comparator: Usual care group (coronary function results not disclosed)
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.
Diagnostic Test: Stratified medicine involving a diagnostic intervention
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)).




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Feasibility of the stratified medicine approach defined by protocol compliance as measured by deviations from the protocol. [ Time Frame: Through study completion, 3 years ]
    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

  2. Procedure-related serious adverse events [ Time Frame: Day 1 (index coronary angiogram procedure) ]
    Safety as reflected by the occurrence of procedure-related serious adverse events

  3. Prevalence of endotypes [ Time Frame: Day 1 ]
    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).

  4. Diagnostic utility of the diagnostic intervention [ Time Frame: Day 1 ]
    Impact of disclosure of the coronary function test results on the diagnosis and certainty of the diagnosis (diagnostic utility)

  5. Clinical utility of the stratified approach [ Time Frame: Day 1 ]
    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)

  6. Cardiovascular risk factors [ Time Frame: Day 1 ]
    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.

  7. Anxiety and depression [ Time Frame: Through study completion, 3 years ]
    Assess the participants' self-reported levels of anxiety and depression using the Patient Health Questionnaire-4 (PHQ-4)

  8. Treatment satisfaction [ Time Frame: Through study completion, 3 years ]
    Assess the participants' self-reported levels of treatment satisfaction using the Treatment Satisfaction Questionnaire for Medication (TSQM)

  9. Illness perception [ Time Frame: Through study completion, 3 years ]
    Assess the participants' perception of their illness using the brief Illness Perception Questionnaire

  10. Health status EQ5D [ Time Frame: Through study completion, 3 years ]
    Assess the participants' general health status and self reported quality of life using the EQ5D questionnaire.

  11. Health status (Seattle Angina Score) [ Time Frame: Through study completion, 3 years ]
    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.

  12. Biomarkers [ Time Frame: 36 months ]
    Assess associations between circulating molecules that are implicated in the pathophysiology of disorders of coronary function.

  13. Health economics [ Time Frame: 36 months ]
    Assess resource utilisation including primary and secondary care costs for tests, procedures and out-patient visits, and medicines, between the randomised groups

  14. Myocardial perfusion [ Time Frame: 42 days ]
    Assess the diagnostic accuracy of stress perfusion magnetic resonance imaging for identification of endotypes based on reference tests of coronary function.

  15. Incidental findings [ Time Frame: 42 days ]
    Detection of clinically significant (actionable) incidental findings using magnetic resonance imaging. The incidental findings may be cardiac or non-cardiac.

  16. Myocardial tissue characterisation [ Time Frame: 42 days ]
    Detection of myocardial pathology using multiparametric CMR



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

A clinically-indicated plan for invasive coronary angiography. Symptoms of angina or angina-equivalent (according to the Rose- and Seattle Angina questionnaires).

Exclusion Criteria:

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03193294


Locations
United Kingdom
Golden Jubilee National Hospital
Clydebank, Dunbartonshire, United Kingdom, G814DY
Hairmyres Hospital
East Kilbride, Lanarkshire, United Kingdom, G75 8RG
Sponsors and Collaborators
NHS National Waiting Times Centre Board
British Heart Foundation
Investigators
Study Director: Katriona Brooksbank, PhD University of Glasgow

Additional Information:
Publications:

Responsible Party: Colin Berry, Professor of Cardiology and Imaging, NHS National Waiting Times Centre Board
ClinicalTrials.gov Identifier: NCT03193294     History of Changes
Other Study ID Numbers: 16CARD25
First Posted: June 20, 2017    Key Record Dates
Last Update Posted: March 13, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Data access may be possible pending Sponsor approval

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Angina Pectoris
Coronary Disease
Coronary Artery Disease
Angina, Stable
Coronary Vasospasm
Chest Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Signs and Symptoms
Arteriosclerosis
Arterial Occlusive Diseases