SOdium-glucose CO-transporter inhibition in patients with Type 2 Diabetes and Ischemic Heart Failure

Phase 1

• Conditions: Patients with type 2 diabetes mellitus and heart failure of ischemic origin; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2015-005715-32-SE
• Lead Sponsor: Karolinska Institutet Stockholm, Sweden

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-02-16
• Last Update Posted: 26 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Age = 18 years
2. Known T2DM (according to current WHO criteria) with HbA1c 48-86 mmol/mol (DCCT 5.6-10%; [57]).
3. Chronic HF of ischemic origin (established according to current European Guidelines; Ischemic etiology defined as history of myocardial infarction given by typical ECG-changes (Q-wave or LBBB), previous PCI or CABG, symptoms typical of angina pectoris with coronary artery disease verified by an exercise test, non-invasive imaging or coronary angiography, since at least two months [58].
4. Signed informed consent to trial participation consistent with ICH-GCP guidelines and local legislations

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

1. Age > 75 years
2. Contraindications to magnetic resonance imaging
a) Implanted devices such as pacemaker or implantable cardioverter defibrillator
b) Severe claustrophobia
3. Serum creatinine estimated glomerular filtration rate < 30 ml/min/1.73m2
4. Intolerance or contraindications to iv adenosine infusion, including clinically important asthma Patients with chronic obstructive pulmonary disease (COPD) should have a lung function test with reversibility testing performed within 12 month before study inclusion. The patient can be included if FEV1.0 is >60% of expected normal value and the reversibility test result should be <10% of the initial FEV1.0 value.
5. Patients with severe concomitant disease (i.e. malignancy, liver failure) or chronic HF due to valvular disorders.
6. Patients who, in the opinion of the investigator, will have difficulties to comply with the protocol (examples: problems to self-monitor glucose, linguistic problems, resident outside of the catchment area, alcohol or drug abuse, psychiatric disorder)
7. Planned for intervention with at discharge are planned for Coronary Artery Bypass Grafting, Percutaneous Coronary Intervention or cardiac device treatment

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To test the hypothesis that empagliflozin (Jardiance™) 25 mg once daily for four months improves myocardial function, structure and coronary flow reserve measured by means of cardiac magnetic resonance in patients with T2DM and HF of ischemic origin. ;Secondary Objective: Not applicable;Primary end point(s): Primary endpoints are<br>1. Improvement in LV systolic and diastolic function (an increase in LV ejection fraction, a reduction in LV filling pressures and a decrease in the LV end diastolic volume) measured by cardiovascular magnetic resonance (CMR) and echocardiography<br>2. An increase in coronary flow reserve measured by rest/adenosine coronary sinus phase contrast flow and rest/adenosine quantitative first pass myocardial perfusion<br>3. Decrease in the left ventricular end-diastolic volume and myocardial extracellular volume (ECV)<br>;Timepoint(s) of evaluation of this end point: After 4 months on active treatment

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Reduction in the NT-pro BNP levels<br>2. Changes in blood volume evaluated by Hematocrit, Hb and radiolabelled albumin <br>3. Improvement in endothelial function <br>4. Decrease in arterial stiffness<br>5. Reduction of expressions of inflammatory activation and oxidative stress<br>6. Hospitalizations for HF <br>;Timepoint(s) of evaluation of this end point: After 4 months on active treatment