Clinical trial NCT04541797: Stress Cardiac Magnetic Resonance of Asymptomatic Type 2 Diabetics with Cardiovascular High Risk to Measure Empagliflozin Impact on Myocardial Blood Flow (CATCH-EM)
Official title: Stress Cardiac Magnetic Resonance of Asymptomatic Type 2 Diabetics with Cardiovascular High Risk to Measure Empagliflozin Impact on Myocardial Blood Flow (CATCH-EM)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Type 2 Diabetes
Microvascular Coronary Artery Disease
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2020-09-09
Enrollment: 160
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double blinded randomised control trial study
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 36 months
measure: Cut-off value for maximum upslope ratio to predict ≥10% increase in myocardial blood flow as result of empagliflozin.
timeFrame: 36 months
measure: Cut-off value for myocardial perfusion index to predict ≥10% increase in myocardial blood flow as result of empagliflozin.
timeFrame: 36 months
measure: Changes in coronary artery plaque volumes between patients receiving empagliflozin and patients not receiving empagliflozin
timeFrame: 36 months
Secondary outcomes:
measure: Change in myocardial blood flow (MBF) in the intervention arm patients comparing patients with positive stress CMR to patients with negative stress CMR.
timeFrame: 36 months
measure: Left ventricular ejection fraction.
timeFrame: 36 months
measure: Left ventricular volumes.
timeFrame: 36 months
measure: Left ventricular myocardial mass.
timeFrame: 36 months
measure: Right ventricular ejection fraction.
timeFrame: 36 months
measure: Right ventricular volumes.
timeFrame: 36 months
measure: Right ventricular myocardial mass.
timeFrame: 36 months
measure: Composite of empagliflozin therapy complication (eg. Urinary tract infection, acute renal failure).
timeFrame: 36 months
measure: Progression in patient symptoms diagnoses.
timeFrame: 36 months
measure: Improvement in exercise tolerance through performing a cardiopulmonary exercise test.
timeFrame: 36 months
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong
Study officials:
References: