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Coronary Microvascular Function and CT Coronary Angiography (CorCTCA) (CorCTCA)

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ClinicalTrials.gov Identifier: NCT03477890
Recruitment Status : Recruiting
First Posted : March 27, 2018
Last Update Posted : March 27, 2018
Sponsor:
Collaborators:
University of Glasgow
British Heart Foundation
Chief Scientist Office of the Scottish Government
NHS Greater Clyde and Glasgow
Information provided by (Responsible Party):
Colin Berry, NHS National Waiting Times Centre Board

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.

Condition or disease Intervention/treatment Phase
Angina, Stable Angina Pectoris, Variant Microvascular Angina Diagnostic Test: Stratified medicine involving a diagnostic intervention Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, double-blind, parallel group, prospective
Masking: Single (Participant)
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. Coronary function is measured in all participants.
Primary Purpose: Diagnostic
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
Actual Study Start Date : August 31, 2017
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : August 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Intervention group (coronary function test results disclosed)
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

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).

Other Name: Adjunctive tests of coronary disease severity and function (disclosed)

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 and protocol adherence is prospectively monitored.
Diagnostic Test: Stratified medicine involving a diagnostic intervention

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 non-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).

Other Name: Adjunctive tests of coronary disease severity and function (not disclosed, sham control)




Primary Outcome Measures :
  1. Final diagnosis [ Time Frame: Day 1 ]
    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.


Secondary Outcome Measures :
  1. Occurrence of abnormal coronary function in a major epicardial coronary artery [ Time Frame: Day 1 ]
    To determine the prevalence of microvascular and/or vasospastic angina at the end of the invasive diagnostic procedure (including the coronary angiogram and coronary function tests) in the study population defined as having non obstructive artery disease (CAD) or none as revealed by a CT coronary angiogram for the investigation of known or suspected CAD.

  2. Presence of an obstructive or flow-limiting stenosis in a major coronary artery. [ Time Frame: Day 1 ]
    Assess the prevalence of obstructive CAD (e.g. FFR≤0.80) at the time of invasive coronary angiography.

  3. Procedure-related serious adverse events [ Time Frame: Day 1 ]
    Safety as reflected by the occurrence of procedure-related serious adverse events

  4. 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).

  5. Cardiovascular risk [ Time Frame: Day 1 ]
    Assess the cardiovascular risk of the participants at baseline, as reflected by the validated JBS3 risk score http://www.jbs3risk.com/

  6. 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, a 4 item inventory rated on a 4 point Likert-type scale (0-3 per item, with a maximum reported score of 6 for anxiety and 6 for depression).

  7. 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) (scale categories, 2 to 7; a higher response reflects higher treatment satisfaction).

  8. Illness perception [ Time Frame: Through study completion, 3 years ]
    Assess the participants' perception of their illness using the Brief Illness Perception Questionnaire, a 9 item scale reflecting the cognitive and emotional representations of illness. Each item is analysed individually.

  9. Health status EQ-5D [ Time Frame: Through study completion, 3 years ]
    Assess the participants' general health status and self reported quality of life using the EQ5D questionnaire. Health status is measured in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression (each is scored on a scale of 1 to 5, with a score of 5 representing the most severe problems or limitations). The visual analog scale ranges from 0 to 100 units, with higher values representing a better outcome.

  10. 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 closeout using the Seattle Angina Questionnaire. The secondary outcome is the within-subject change in Seattle Angina Score score over time.

  11. Functional status [ Time Frame: Through study completion, 3 years ]
    To assess functional status and activity levels as reflected by the Duke Activity Status Index (DASI) at baseline and during follow-up.

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

  13. Serum troponin concentration [ Time Frame: Through study completion, 3 years ]
    Assess associations between circulating concentrations of troponin I protein (ng/L) that may be implicated in the pathophysiology of disorders of coronary function.

  14. Physical activity [ Time Frame: Through study completion, 3 years ]
    To assess physical activity levels as reflected by the International Physical Activity Questionnaire - Short Form (IPAQ-SF) with units of activity expressed in minutes/week at baseline and during follow-up. Patients are classified as inactive, moderately active, or HEPA (health-enhancing physical activity) active, depending on how much vigorous/moderate/light exercise they do in a week.

  15. Plasma endothelin-1 [ Time Frame: Through study completion, 3 years ]
    Assess the circulating concentration of big endothelin-1 (pg/mL) peptide in plasma at sampling time-points, baseline and during follow-up. Big endothelin-1 is the stable pre-cursor of endothelin-1 and big endothelin-1 is more stable than endothelin-1 so the former is intended to be measured.



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

Inclusion Criteria:

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

Exclusion Criteria:

  1. A health problem that would explain the angina, e.g. anaemia, moderate-severe aortic stenosis, hypertrophic obstructive cardiomyopathy
  2. 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
  3. Lack of informed consent.

    Exclusion from randomisation in the catheter laboratory:

  4. Flow-limiting coronary disease defined by a fractional flow reserve (FFR) ≤0.80 in an artery>2.5 mm.

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): NCT03477890


Contacts
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Contact: Colin Berry, PhD FRCP 01419515180 colin.berry@glasgow.ac.uk
Contact: Novalia Sidik, MRCP 01419515180 n.sidik@nhs.net

Locations
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United Kingdom
Golden Jubilee National Hospital Recruiting
Clydebank, Dunbartonshire, United Kingdom, G814DY
Contact: Colin Berry, PhD FRCP    01419515180    colin.berry@glasgow.ac.uk   
Contact: Novalia Sidik, MRCP    01419515180    n.sidik@nhs.net   
Principal Investigator: Colin Berry, PhD FRCP         
Sub-Investigator: Tom J Ford, MRCP         
Sub-Investigator: David S Corcoran, MRCP         
Sub-Investigator: Margaret McEntegart, PhD FRCP         
Sub-Investigator: Keith G Oldroyd, MDHons FRCP         
Sub-Investigator: John Byrne, MD FRCP         
Sub-Investigator: Jacqueline Adams, MD FRCP         
Sub-Investigator: David Stobo, FRCR         
Forth Valley Royal Hospital Recruiting
Larbert, Forth Valley, United Kingdom, FK5 4WR
Contact: Novalia Sidik, MRCP    01324 566000    n.sidik@nhs.net   
Principal Investigator: Allister Hargreaves, MD FRCP         
Sub-Investigator: Novalia Sidik, MRCP         
Glasgow Royal Infirmary Recruiting
Glasgow, Strathclyde, United Kingdom, G4 0SF
Contact: Novalia Sidik, MRCP    01412114000    n.sidik@nhs.net   
Principal Investigator: Giles Roditi, FRCR         
Sub-Investigator: Novalia Sidik, MRCP         
Sponsors and Collaborators
NHS National Waiting Times Centre Board
University of Glasgow
British Heart Foundation
Chief Scientist Office of the Scottish Government
NHS Greater Clyde and Glasgow
Investigators
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Study Director: Katriona Brooksbank, PhD University of Glasgow

Publications:

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Responsible Party: Colin Berry, Professor of Cardiology and Imaging, NHS National Waiting Times Centre Board
ClinicalTrials.gov Identifier: NCT03477890     History of Changes
Other Study ID Numbers: 17/CARD/25
First Posted: March 27, 2018    Key Record Dates
Last Update Posted: March 27, 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

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

Additional relevant MeSH terms:
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Angina Pectoris
Angina, Stable
Angina Pectoris, Variant
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Neurologic Manifestations
Signs and Symptoms
Angina, Unstable