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

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.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes; Microvascular Coronary Artery Disease
• Intervention / Treatment: Drug: Placebo; Diagnostic test: Stress Cardiac Magnetic Resonance; Drug: Empagliflozin 10 MG

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.

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ming-Yen NG, BMBS; Phone Number: (+852) 22552524; Email: myng2@hku.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • The University of Hong Kong
    • Contact: Ming-Yen NG, BMBS; Phone Number: (+852) 22554524; Email: myng2@hku.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control; 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; 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).; Diagnostic test: Stress Cardiac Magnetic Resonance; Imaging: All patients will have stress CMR examinations at recruitment.; Other Names: Stress CMR
Experimental: Intervention; Patients will be prescribed empagliflozin 10mg once a day and optimised medical therapy for 6 months and standard follow-up like the control group.	Diagnostic test: Stress Cardiac Magnetic Resonance; Imaging: All patients will have stress CMR examinations at recruitment.; Other Names: Stress CMR; Drug: Empagliflozin 10 MG; 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.; Other Names: Empagliflozin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: July 8, 2020
• First Submitted That Met QC Criteria: September 7, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: UW 19-010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No