Studies of Empagliflozin and Its Cardiovascular, Renal and Metabolic Effects (SUGAR)
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|ClinicalTrials.gov Identifier: NCT03485092|
Recruitment Status : Recruiting
First Posted : April 2, 2018
Last Update Posted : May 31, 2018
|Condition or disease||Intervention/treatment||Phase|
|Heart Failure Diabetes Mellitus||Drug: Empagliflozin 10 MG Drug: Placebo Oral Tablet||Phase 4|
The results of the EMPA-REG OUTCOME trial on CVD outcomes and heart failure hospitalisation suggests that empagliflozin works quickly to lessen CVD mortality and reduce heart failure hospitalisations in patients with diabetes and existing cardiovascular disease. The lack of effect on non-fatal MI and stroke would suggest limited impact on atherothrombotic mechanisms. It is important to understand the mechanisms by which empagliflozin is acting in more detail, in order that the drug can be more widely targeted at patient groups that might benefit most; particularly patients with heart failure and diabetes (as discussed in the rationale).
The investigators have hypothesised, in a detailed published review (3), that the benefit derives from the specific effects of sodium-glucose linked transporter-2 (SGLT2) inhibition on renal sodium and glucose handling, leading to both diuresis and improvements in diabetes-related maladaptive renal arteriolar responses. These haemodynamic and renal effects are likely to be beneficial in patients with clinical or subclinical cardiac dysfunction. The net result of these processes is an improvement in cardiac systolic and diastolic function and, thereby, a lower risk of heart failure hospitalisation (HFH) and sudden cardiac death.
The investigators have therefore designed the present trial to perform a comprehensive clinical trial to interrogate in detail the effects of empagliflozin on specific pathways (inclusive of cardiac and renal effects) in patients with type 2 diabetes and heart failure.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||130 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Randomised, placebo controlled trial|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||placebo controlled trial|
|Official Title:||Studies of Empagliflozin and Its Cardiovascular, Renal and Metabolic Effects in Patients With Diabetes Mellitus and Heart Failure (SUGAR-DM-HF)|
|Actual Study Start Date :||March 16, 2018|
|Estimated Primary Completion Date :||February 28, 2020|
|Estimated Study Completion Date :||February 28, 2020|
Active Comparator: Empagliflozin
Empagliflozin 10mg tablets for oral self-administration once daily
Drug: Empagliflozin 10 MG
Empagliflozin 10mg tablets for oral self administration once a day
Placebo Comparator: Placebo Oral Tablet
placebo tablets for oral self-administration once daily
Drug: Placebo Oral Tablet
placebo tablets for oral self administration once a day
- Left Ventricular End Systolic Volume Index (LVESVI) [ Time Frame: 40 weeks ]left ventricular end-systolic volume index measured by cardiac magnetic resonance imaging as mL/m2
- left ventricular global longitudinal strain [ Time Frame: 40 weeks ]left ventricular global longitudinal strain measured by cardiac magnetic resonance imaging GLS%
- microvascular perfusion [ Time Frame: 40 weeks ]microvascular perfusion measured by Gadolinium enhanced Cardiac magnetic resonance imaging measured as ml/min/g
- extracellular volume fraction [ Time Frame: 40 weeks ]extracellular volume fraction measured by Gadolinium enhanced Cardiac magnetic resonance imaging measured as %
- Quality of Life (QoL) score [ Time Frame: 40 weeks ]
quality of life (QoL) score measured by Kansas City Cardiomyopathy Questionnaire, function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.
This instrument was developed and validated by John Spertus. John is Director of Cardiovascular Education and Outcomes Research at the Mid America Heart Institute, and he is also a Professor of Medicine at the University of Missouri - Kansas City.
In the KCCQ, an overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. For brevity, only the performance characteristics of the overall summary score are presented in this discussion.
- Exercise Capacity [ Time Frame: 40 weeks ]Exercise capacity measured by six minute walk test measured in m
- hepatic injury [ Time Frame: 40 weeks ]hepatic injury defined by the following alterations of liver parameters after randomisation at Visit 1: (a) elevation of aspartate transaminase and/or alanine transaminase ≥3 fold upper limit of normal combined with an elevation of total bilirubin ≥2 fold upper limit of normal measured in the same blood draw sample; (b) isolated elevation of aspartate transaminase and/or alanine transaminase ≥5 fold upper limit of normal irrespective of any bilirubin elevation
- renal dysfunction [ Time Frame: 40 weeks ]renal dysfunction defined by creatinine value ≥2 fold increase from baseline and is above the upper limit of normal
- hyperkalaemia [ Time Frame: 40 weeks ]hyperkalaemia defined by any potassium lab measure ≥5.5 mmol/L
- metabolic acidosis [ Time Frame: 40 weeks ]metabolic acidosis defined by serum bicarbonate ≤18 mmol/L
- myocardial metabolic activity [ Time Frame: 40 weeks ]myocardial metabolic activity defined by PCr:ATP ratio (measured by 31P magnetic resonance spectroscopy
- total renal blood flow measured by magnetic resonance imaging [ Time Frame: 40 weeks ]total renal blood flow measure using cardiac magnetic resonance imaging measured as ml/min/100g
- regional renal blood flow measured by magnetic resonance imaging [ Time Frame: 40 weeks ]regional renal blood flow measure using cardiac magnetic resonance imaging measured as ml/min/100g
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03485092
|Contact: Mathew Lee, MBCHB||0141 330 2237||Matthew.Lee.email@example.com|
|Contact: katriona brooksbank, PhD||0131 330 firstname.lastname@example.org|
|Queen Elizabeth University Hospital||Recruiting|
|Glasgow, Scotland, United Kingdom, G51 4TF|
|Contact: Mathew Lee, MBChB 0141 232 7600 email@example.com|
|Contact: Ann Wright, RCN 0141 232 7600 firstname.lastname@example.org|
|Principal Investigator: Mark Petrie, MBChB|
|Study Chair:||Naveed Sattar, PhD||Glasgow University and NHS GGC|