Chronic heart failure with left ventricular systolic dysfunction MedDRA version: 20.0 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 100000004849 MedDRA version: 20.0 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 100000004849
Conditions
Sponsors
NHS Greater Glasgow and Clyde
University of Glasgow
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Written informed consent Male or female, aged =18 years age Type 2 DM (diet-controlled or on stable treatment) or prediabetes o Stable treatment defined as no change in oral therapy agents or doses for diabetes mellitus and (where applicable) =65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: • Type 1 DM • History of hospital admission with a diagnosis of diabetic ketoacidosis (DKA) • Insulin use within 1 year of diagnosis of diabetes • History of acute or chronic pancreatitis and on insulin treatment for diabetes or low residual c-peptide (random non-fasting level of 60 ml/min/1.73m2; (b) within last 3 months in patients with eGFR 45-60 ml/min/1.73m2; (c) within last 1 month in patients with eGFR 30-44 ml/min/1.73m2) • Persistent/permanent atrial fibrillation/flutter (conditions which significantly impede MRI image interpretability) • Acute coronary syndrome, stroke or surgery within 1 month (small type 2 MI in the context of acute HF does not apply) • BMI >52kg/m2 • Liver disease, defined by serum levels of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal (ULN) at the time of screening (based on latest available result; liver function tests will be repeated at the time of screening if there are no recent (within last 6 months) results in patients without known liver disease) • Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption • Any condition outside the cardiovascular and renal disease area, such as but not limited to malignancy, with a life expectancy of less than 2 years based on investigator’s clinical judgement • Active malignancy requiring treatment at the time of visit 1 (with the exception of successfully treated basal cell or treated squamous cell carcinoma, adjuvant hormonal therapy for breast cancer and hormone therapy for prostate cancer) • Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells (e.g. malaria, babesiosis, haemolytic anaemia) which in the opinion of the investigator are clinically significant • Treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent • Any uncontrolled endocrine disorder except Type 2 DM or prediabetes • Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance with study procedures or study drug intake • Known hypersensitivity to the empagliflozin or excipients • Known hypersensitivity to gadolinium • Inability to give informed consent • SGLT2 inhibitor use (current or previous) • Devices or any other contraindication to MRI scans • Currently pregnant, planning pregnancy, or currently breastfeeding • History of previous lower limb amputation (non-traumatic) • Current participation in another interventional medical study or within the last 90 days • Anyone who, in the investigators’ opinion, is not suitable to participate in the trial for other reasons.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the effect of empagliflozin on heart structure and function (as measured by MRI scan of the heart) in patients with type 2 diabetes mellitus (or prediabetes) and heart failure.;Secondary Objective: Secondary Objectives: To examine the effect of empagliflozin on: • microvascular perfusion and extracellular volume fraction (Gd-CMR), • quality of life scores, • exercise capacity • laboratory tests (heart, kidney, endocrine) pulmonary congestion (lung ultrasound) To examine the effect of empagliflozin on safety including liver injury, renal failure, high potassium, and pH imbalance (metabolic acidosis). Experimental Secondary Objectives (may not be completed for all patients): • To examine the effect of empagliflozin on myocardial metabolic activity defined by PCr:ATP ratio at 31P MR spectroscopy (substudy) • To examine the effect of empagliflozin on total and regional renal blood flow using CMR Research Only Objectives: • To examine the effect of empagliflozin on biomarker profile • To examine the effect of empagliflozin on DNA and epigenetics • To examine the effect of empagliflozin on Bioelectrical Impedance Analysis (BIA);Primary end point(s): Co-primary outcomes: Cardiac Structure: To examine the effect of empagliflozin on left ventricular end-systolic volume index (LVESVI) by cardiac magnetic resonance imaging on active treatment versus placebo. Cardiac Function: To examine the effect of empagliflozin on left ventricular global longitudinal strain by cardiac magnetic resonance imaging on active treatment versus placebo.;Timepoint(s) of evaluation of this end point: Week 0, week 36 and week 40 (optional). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Objectives: • To examine the effect of empagliflozin on microvascular perfusion and extracellular volume fraction (Gd-CMR) • To examine the effect of empagliflozin on quality of life score • To examine the effect of empagliflozin on exercise capacity • To examine the effect of empagliflozin on biomarker profile • To examine the effect of empagliflozin on safety outcomes including hepatic injury, renal dysfunction, hyperkalaemia and metabolic acidosis to examine the effects of empagliflozin on pulmonary congestion (lung ultrasound) Experimental Secondary Objectives (may not be completed for all patients): • To examine the effect of empagliflozin on myocardial metabolic activity defined by PCr:ATP ratio at 31P MR spectroscopy (substudy) • To examine the effect of empagliflozin on total and regional renal blood flow using CMR Research Only Objectives: • To examine the effect of empagliflozin on biomarker profile • To examine the effect of empagliflozin on DNA and epigenetics • Bioelectrical impedance analysis;Timepoint(s) of evaluation of this end point: Week 0, week 12 (except CMR and MR spectroscopy), week 36 and week 40 (optional). | — |
Countries
United Kingdom
Contacts
Public ContactProfessor Naveed Sattar
University of Glasgow
Outcome results
None listed