Stress Cardiac Magnetic Resonance of Asymptomatic Type 2 Diabetics With Cardiovascular High Risk to Measure Empagliflozin Impact on Myocardial Blood Flow (CATCH-EM)

Study Overview
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Brief Summary
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The study design is a double blinded randomised control trial study that aims to conduct a randomised controlled trial of empagliflozin and determine if empagliflozin will improve myocardial blood flow in asymptomatic high risk type 2 diabetic patients. Also, to determine a cut-off using maximum upslope ratio and myocardial perfusion reserve index in which patients would demonstrate an improvement in myocardial blood flow.

Detailed Description
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It is unknown whether empagliflozin will improve myocardial blood flow and resolve myocardial ischaemia caused by microvascular coronary artery disease in asymptomatic patients with type 2 diabetes.This study proposes to perform a randomised controlled trial to compare optimised medical therapy against empagliflozin in addition to optimised medical therapy to improve myocardial blood flow as measured by stress CMR. This trial would provide evidence if 10mg of empagliflozin given for 6 months could be an indicated treatment in asymptomatic high risk type 2 diabetic patients using stress CMR. The duration of 6 months is slightly longer than the mouse study (ie. 5 months) which showed an improvement in myocardial blood flow but not too long that the risk of increased patient withdrawal from the study will occur. All patients will undergo coronary CT angiography in order to assess degree of coronary artery narrowing non-invasively before allocation to the control or intervention group. Patients will also undergo coronary CT angiography at the end of the study after 6 months of placebo or empagliflozin.

Official Title
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Stress Cardiac Magnetic Resonance of Asymptomatic Type 2 Diabetics With Cardiovascular High Risk to Measure Empagliflozin Impact on Myocardial Blood Flow (CATCH-EM)

Conditions
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Type 2 Diabetes, Microvascular Coronary Artery Disease

Intervention / Treatment
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* Drug: Empagliflozin 10 MG
* Drug: Placebo
* Diagnostic Test: Stress Cardiac Magnetic Resonance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Onset of type 2 diabetes at ≥30yrs old with no history of ketoacidosis 40-90yrs old Any 2 risk factors which include: i) Smoking (ie. current or ex-smokers) ii) Dyslipidaemia (defined as low density lipoprotein ≥2.6mmol/L, triglyceride >1.7mmol/L or decreased high density lipoprotein cholesterol <1.04mmol/L [man] or <1.29mmol/L [woman] or on lipid-lowering agent)(17, 18) iii) Hypertension (ie. systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg or patients treated for hypertension) iv) Obesity (using definition adapted for chinese ethnicity, body mass index >25kg/m2)(19) v) Family history of premature heart disease (defined as 1st degree relative [ie. parent or sibling] with development of atherosclerotic cardiovascular disease or cardiovascular related death <55 years of age in male and <65 years of age in female) HbA1c ≥ 6.5% and <10.0% Exclusion Criteria: Angina pectoris or chest discomfort Prior coronary artery bypass grafts Coronary artery stenting within 6 months of study enrolment Previous myocardial infarct Any contraindication for stress CMR testing Renal impairment with eGFR <45ml/min/1.73m2 Limited life expectancy <5 years, for example due to pulmonary disease, cancer or significant hepatic failure Contraindication to dual antiplatelet therapy Contraindication to empagliflozin or other SGLT2 inhibitors Unable to take empagliflozin Patients currently on empagliflozin or given empagliflozin in the last 6 months Planned need for concomitant cardiac surgery or coronary intervention Refusal or inability to sign an informed consent. Potential for non-compliance towards the requirements in the trial protocol (especially the medical treatment) or follow-up visits

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double blinded randomised control trial study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>Patients will have placebo and optimised medical therapy and will continue to have protocol driven therapy and follow-up appointments (currently 1 appointment every 3 months). | Drug: Placebo<br>* Control group: Patients will have placebo and optimised medical therapy and will continue to have protocol driven therapy and follow-up appointments (currently 1 appointment every 3 months).<br>Diagnostic Test: Stress Cardiac Magnetic Resonance<br>* Imaging: All patients will have stress CMR examinations at recruitment.<br>* Other names: Stress CMR;|
| Experimental: Intervention<br>Patients will be prescribed empagliflozin 10mg once a day and optimised medical therapy for 6 months and standard follow-up like the control group. | Drug: Empagliflozin 10 MG<br>* Intervention group: Patients will be prescribed empagliflozin 10mg once a day and optimised medical therapy for 6 months and standard follow-up like the control group.<br>* Other names: Empagliflozin;Diagnostic Test: Stress Cardiac Magnetic Resonance<br>* Imaging: All patients will have stress CMR examinations at recruitment.<br>* Other names: Stress CMR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in myocardial blood flow as measured by stress CMR (ie. maximum upslope ratio and myocardial perfusion reserve index) between patients receiving empagliflozin and patients not receiving empagliflozin. |  | 36 months | 
| Cut-off value for maximum upslope ratio to predict ≥10% increase in myocardial blood flow as result of empagliflozin. |  | 36 months | 
| Cut-off value for myocardial perfusion index to predict ≥10% increase in myocardial blood flow as result of empagliflozin. |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in myocardial blood flow (MBF) in the intervention arm patients comparing patients with positive stress CMR to patients with negative stress CMR. |  | 36 months | 
| Left ventricular ejection fraction. |  | 36 months | 
| Left ventricular volumes. |  | 36 months | 
| Left ventricular myocardial mass. |  | 36 months | 
| Right ventricular ejection fraction. |  | 36 months | 
| Right ventricular volumes. |  | 36 months | 
| Right ventricular myocardial mass. |  | 36 months | 
| Composite of empagliflozin therapy complication (eg. Urinary tract infection, acute renal failure). |  | 36 months | 
| Progression in patient symptoms diagnoses. | The Seattle Angina Questionnaire (SAQ) will be administered at time of baseline CMR and at follow-up CMR in order to determine if there is an improvement in patient symptoms. | 36 months | 
| Improvement in exercise tolerance through performing a cardiopulmonary exercise test. |  | 36 months |