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Trial registered on ANZCTR


Registration number
ACTRN12618001533280
Ethics application status
Approved
Date submitted
4/07/2018
Date registered
13/09/2018
Date last updated
7/12/2020
Date data sharing statement initially provided
21/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Possible causes of heart attack without coronary artery blockages.
Scientific title
Coronary Vasomotor Function in Myocardial Infarction with NonObstructive Coronary Arteries (MINOCA)
Secondary ID [1] 295387 0
None
Universal Trial Number (UTN)
Not applicable
Trial acronym
MINOCA - CATH Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myocardial Infarction 308621 0
Condition category
Condition code
Cardiovascular 307568 307568 0 0
Coronary heart disease

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The study procedures will begin following the participant's coronary angiogram diagnostic procedure. The coronary angiogram will be participant's standard care whereas the combowire and Optical Coherence Tomography (OCT) assessments will be provided as part of this study procedure.

Combowire Assessments: A wire will be passed into one of the coronary arteries that will allow us to measure the pressure and blood flow down the artery. This method allows us to measure the function of the small (microscopic) arteries. Adenosine is the agent used to dilate the microscopic arteries. This agent is given intravenously through an intravenous cannula. This intravenous cannula is routinely put in an arm vein prior to a coronary angiogram. In addition to dilating the small microscopic (small) arteries. Adenosine will be given for 2 minutes and necessary angiographic images will be taken and hemodynamics assessments will be performed. Following which, Glyceryl trinitrate (GTN) will be administered as intra coronary injection and the additional angiographic image will be taken.

OCT Assessments: The combo wire will be removed and the OCT catheter will be inserted and the contrast agent will be injected. The imaging will be done in about 3 seconds, and the entire coronary artery will be imaged.

It would take approximately 15 minutes to complete combowire and OCT assessments.

Cardiac magnetic resonance imaging (MRI) Assessments: Within 5 days of the participant's initial presentation, they will undergo a cardiac MRI procedure. This is part of the participant's routine clinical management

Health Status Assessments: Study participants will then followed up to 12 Months (1 Month, 6 Months and 12 Months) will the quality of life assessment questionnaires via telephone.
Intervention code [1] 301704 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 306547 0
To determine the prevalence of coronary microvascular dysfunction as determined by an abnormal HMR (HMR>1.9) in MINOCA patients, during their acute presentation.

The ComboWire is a steerable guidewire with a pressure transducer mounted proximal to the tip and a tip mounted ultrasound transducer. The ComboWire measures pressure and flow velocity when used with the ComboMap Instrument. HMR will be calculated as the ratio between hyperaemic mean distal pressure and hyperaemic average Doppler flow peak velocity (APV). The calculations will be driven from ComboMap system in a semi-automated manner.
Timepoint [1] 306547 0
In-Hospital
Secondary outcome [1] 349849 0
To determine the prevalence of abnormal coronary haemodynamic measure defined as Fractional Flow Reserve (FFR) less than 0.8 in patients with MINOCA during the acute presentation.

The FFR values will be driven from the ComboMap system. FFR will be calculated as the ratio of the mean distal pressure to the mean aortic pressure during maximum hyperemia. The calculations will be driven from ComboMap system in a semi-automated manner.
Timepoint [1] 349849 0
In Hospital
Secondary outcome [2] 349850 0
To determine the prevalence of abnormal coronary haemodynamic measure defined as Coronary Flow Reserve (CFR) less than 2.0 in patients with MINOCA during the acute presentation.

The CFR values will be driven from the ComboMap system. CFR will be calculated as the ratio of hyperemic to baseline APV. The calculations will be driven from ComboMap system in a semi-automated manner.
Timepoint [2] 349850 0
In Hospital
Secondary outcome [3] 349851 0
To determine the prevalence of abnormal coronary haemodynamic measure: Epicardial artery tone index less than 100% in patients with MINOCA during the acute presentation.

Epicardial coronary tone index is calculated as: ((Post GTN vessel diameter- Pre GTN vessel diameter)/Pre GTN vessel diameter) X 100.
The measurements will be driven from coronary angiographic images by a trained interventional cardiologist.
Timepoint [3] 349851 0
In Hospital
Secondary outcome [4] 349852 0
To determine the prevalence of OCT assessed plaque rupture in patients with MINOCA, during their acute presentation.

OCT Images will be reviewed by trained cardiologists/researchers based on the definitions and recommendations of the International Working Group for Intravascular OCT Standardization and Validation consensus document.
Timepoint [4] 349852 0
In Hospital
Secondary outcome [5] 349853 0
To determine the prevalence of OCT-assessed Plaque Erosion in patients with MINOCA, during their acute presentation

OCT Images will be reviewed by trained cardiologists/researchers based on the definitions and recommendations of the International Working Group for Intravascular OCT Standardization and Validation consensus document.
Timepoint [5] 349853 0
In Hospital
Secondary outcome [6] 349854 0
To determine the prevalence of OCT-assessed Calcified Plaque Nodule in patients with MINOCA, during their acute presentation

OCT Images will be reviewed by trained cardiologists/researchers based on the definitions and recommendations of the International Working Group for Intravascular OCT Standardization and Validation consensus document.
Timepoint [6] 349854 0
In Hospital
Secondary outcome [7] 349856 0
To determine the prevalence of OCT-assessed Plaque Thrombus in patients with MINOCA, during their acute presentation.

OCT Images will be reviewed by trained cardiologists/researchers based on the definitions and recommendations of the International Working Group for Intravascular OCT Standardization and Validation consensus document.
Timepoint [7] 349856 0
In Hospital
Secondary outcome [8] 349857 0
To determine the cardiac MRI driven cause of initial presentation.

MINOCA presentations may mimic non-ischaemic causes of suspected MI such as Myocarditis or Takotsubo cardiomyopathy. Cardiac MRI is used to confirm the presence of ischemic MI in MINOCA cohort.

The images will be analysed using dedicated software, CVI42 or Phillips intera.
Timepoint [8] 349857 0
MRI will be performed within 5 days post acute presentation.
Secondary outcome [9] 349858 0
To determine the Left ventricle function (Ejection Fraction) as determined by cardiac MRI in MINOCA patients.

The images will be analysed using dedicated software, CVI42 or Phillips Intera. A trained investigator will trace the endocardial and epicardial borders of the left ventricle and calculate ejection fraction in a semi-automated manner.
Timepoint [9] 349858 0
MRI will be performed within 5 days post acute presentation.
Secondary outcome [10] 349859 0
To determine the infarct size in patients with MRI confirmed infarct presence.

The images will be analysed using dedicated software, CVI42 or Phillips intera. A trained investigator will trace the endocardial and epicardial borders of the left ventricle and calculate infarct size in a semi-automated manner.
Timepoint [10] 349859 0
MRI will be performed within 5 days post acute presentation.
Secondary outcome [11] 349860 0
To determine the are at risk in patients with MRI confirmed infarct presence.

The images will be analysed using dedicated software, CVI42 or Phillips Intera. A trained investigator will trace the endocardial and epicardial borders of the left ventricle and calculate area at risk in a semi-automated manner.
Timepoint [11] 349860 0
MRI will be performed within 5 days post acute presentation.
Secondary outcome [12] 349861 0
To determine the location of infarct in ischemic MI confirmed MINOCA patients. The images will be analysed using dedicated software, CVI42 or Phillips Intera.
Timepoint [12] 349861 0
MRI will be performed within 5 days post acute presentation.
Secondary outcome [13] 349862 0
To determine the Angina Frequency – as assessed by Seattle Angina Questionnaire (SAQ).

Angina frequency: measures frequency of angina over the previous 4 weeks.
Timepoint [13] 349862 0
6 weeks, 6 Months and 12 Months.
Secondary outcome [14] 349863 0
To determine the Physical Limitation – as assessed by SAQ

Physical limitation: measures how common daily activities representing low, medium, and high exertional requirements are limited by angina
Timepoint [14] 349863 0
6 weeks, 6 Months and 12 Months.
Secondary outcome [15] 349864 0
To determine the Quality of Life – as assessed by SAQ & Euro-QoL-5D (EQ5D)

The SAQ quantifies patients’ physical limitations caused by angina, the frequency of and recent changes in their symptoms, their satisfaction with treatment, and the degree to which they perceive their disease to affect their quality of life. Each scale is transformed to a score of 0 to 100, where higher scores indicate better function (eg, less physical limitation, less angina, and better quality of life).

The EQ-5D consists of a descriptive system which comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. It can be used as a quantitative measure of health outcome that reflects the patient’s own judgement.
Timepoint [15] 349864 0
6 weeks, 6 Months and 12 Months.
Secondary outcome [16] 349865 0
To determine Depression – as assessed by Patient Health Questionnaire-9 (PHQ-9)

PhQ is a 9-item measure that assesses the severity of depressive symptoms in individuals. Each item on the measure is rated on a 4-point scale (0=Not at all; 1=Several days; 2=More than half the days; and 3=Nearly every day). The total score can range from 0 to 27, with higher scores indicating greater severity of depression.
Timepoint [16] 349865 0
6 weeks, 6 Months and 12 Months.
Secondary outcome [17] 351766 0
To determine the predictors of continuing chest pain after admission using combowire assessments, OCT assessments, cardiac MRI assessments and the health status questionnaires.

It is expected that 25% of MINOCA patients experience continuing chest pain following their first presentation. Using the data generated from this study, we exploratively aim to examine the predictors of this continuing chest pain.
Timepoint [17] 351766 0
In hospital, 6 weeks, 6 months, 12 months.

Eligibility
Key inclusion criteria
1) Patients presenting with the symptoms suggestive of acute non-ST elevation myocardial infarction (NSTEMI) will be approached to participate in this study.
2) Male/Female, Aged equal or above 18 years
3) Acute MI Criteria (Must meet both of the following criteria (a & b)
a) Troponin I or T level greater than the 99th percentile of the upper reference limit (URL)
b) No significant ST segment elevation in ECG
4) Coronary angiography diagnosis of non-obstructive coronary arteries ( less than 50% stenosis or completely normal arteries)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) ST-segment elevation on ECG (ie: STEMI)
2) Thrombolytic therapy within 48 hours of diagnostic angiography.
3) Troponin elevation due to non-ischaemic causes identified prior to coronary angiography
4) Coronary angiography revealing obstructive coronary arteries (above or equal to 50% stenosis)
5) Severe valvular disease – including aortic stenosis (valve gradient more than 50mmHg) mitral regurgitation (regurgitation extending to pulmonary veins), mitral stenosis (valve are less than 1cm2)
6) Significant left ventricular dysfunction as documented by an ejection fraction less than 40%
7) Severe obstructive airways – any prior admission to ICU or general hospital admission in past 12 months for infective exacerbation of airways disease.
8) Active internal bleeding or history of hemorrhagic diathesis (including heparin-induced thrombocytopenia)
9) Major surgery (eg: CABG) or trauma within the previous 6 weeks
10) Non-English speaking
11) Pregnancy
12) Inability to provide informed consent (Compromised mental status, e.g., dementia, too ill)
13) Currently a prisoner
14) Contraindications to drugs and devices (Adenosine, GTN, OCT wire, Combo wire)

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Due to the original nature of this study, power calculations are difficult. In our cohort of stable angina patients (ie no recent MI) with non-obstructive coronary arteries undergoing elective coronary vasomotor assessment, 57% had an abnormal HMR. Montone et al recently reported that 16% of their MINOCA patients had evidence of microvascular spasm. This later entity represents an abnormal constrictor response to Acetylcholine and contrasts to the impaired vasodilator response to adenosine, as reflected in the HMR measure.
Thus, it may be speculated that as few as 16% but as many as 57% of MINOCA patients may have HMR. If we assume that 36% (median value) of the MINOCA patients have an abnormal HMR, then 40 patients would be required to detect a HMR >1.9 with 95% confidence interval at a power of 0.8.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/10/2019
Actual
6/03/2020
Date of last participant enrolment
Anticipated
31/12/2021
Actual
Date of last data collection
Anticipated
31/12/2022
Actual
Sample size
Target
40
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 11292 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [2] 11293 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 18160 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment postcode(s) [1] 23181 0
5011 - Woodville
Recruitment postcode(s) [2] 23182 0
5000 - Adelaide
Recruitment postcode(s) [3] 32157 0
5112 - Elizabeth Vale

Funding & Sponsors
Funding source category [1] 299979 0
Charities/Societies/Foundations
Name [1] 299979 0
The Hospital Research Foundation
Country [1] 299979 0
Australia
Primary sponsor type
University
Name
The University of Adelaide
Address
University of Adelaide- The Queen Elizabeth Hospital campus
Level 5B- Dept of Medicine,
28, Woodville Road
Woodville South
SA 5011
Country
Australia
Secondary sponsor category [1] 299359 0
None
Name [1] 299359 0
Address [1] 299359 0
Country [1] 299359 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300836 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 300836 0
Ethics committee country [1] 300836 0
Australia
Date submitted for ethics approval [1] 300836 0
21/03/2018
Approval date [1] 300836 0
10/04/2018
Ethics approval number [1] 300836 0
HREC/18/CALHN/99

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2853 2853 0 0
/AnzctrAttachments/375479-2018- MINOCA CATH HREC notification approval.pdf (Ethics approval)

Contacts
Principal investigator
Name 84974 0
Dr John Beltrame
Address 84974 0
Level 5B, The Queen Elizabeth Hospital
28, Woodville Road, Woodville South SA 5011
Country 84974 0
Australia
Phone 84974 0
+61 8 8222 6740
Fax 84974 0
Email 84974 0
john.beltrame@adelaide.edu.au
Contact person for public queries
Name 84975 0
John Beltrame
Address 84975 0
Level 5B, The Queen Elizabeth Hospital
28, Woodville Road, Woodville South SA 5011
Country 84975 0
Australia
Phone 84975 0
+61 8 8222 6740
Fax 84975 0
Email 84975 0
john.beltrame@adelaide.edu.au
Contact person for scientific queries
Name 84976 0
John Beltrame
Address 84976 0
Level 5B, The Queen Elizabeth Hospital
28, Woodville Road, Woodville South SA 5011
Country 84976 0
Australia
Phone 84976 0
+61 8 8222 6740
Fax 84976 0
Email 84976 0
john.beltrame@adelaide.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
4183Study protocol  sivabaskari.pasupathy@adelaide.edu.au
4184Informed consent form  sivabaskari.pasupathy@adelaide.edu.au
4185Ethical approval  sivabaskari.pasupathy@adelaide.edu.au



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.