End Stage Renal Disease on Dialysis, Heart Failure with Reduced Ejection Fraction
Conditions
Keywords
end stage renal disease, sodium-glucose co-transporter 2 inhibitors,, heart failure with reduced ejection fraction, empagliflozin, left ventricular mass
Brief summary
In patients with ESRD, up to 20% of patients suffer from HFrEF, leading to significant CV morbidity and mortality. Several drug classes that provide survival benefits for patients with HFrEF, including SGLT2i, lack data regarding their efficacy and safety in patients under chronic hemodialysis. As the primary target of SGLT2i is expressed mostly in the kidneys, the efficacy of SGLT2i in patients with ESRD may be limited. On the other hand, patients with ESRD are at higher risks of experiencing cardiovascular events and may still benefit from treatment. Several mechanistic studies have demonstrated direct actions of SGLT2i on the myocardium, thus it is possible that the benefits of SGLT2i on heart failure are independent of their glycosuric actions and may still be present in anuric subjects. Furthermore, pharmacokinetics and pharmacodynamics studies on empagliflozin demonstrated that peak plasma levels of empagliflozin in subjects with renal failure/ESRD were similar to those in subjects with normal renal function. The use of empagliflozin in patients with ESRD seemed safe in terms of pharmacokinetics and pharmacodynamics, yet its efficacy remains to be explored.
Interventions
DRUGEmpagliflozin 25 MG
The medication will be packed in a customized sealed jar and labeled on the exterior of the jar.
DRUGPlacebo
The placebo tablet is manufactured by Prince Pharmaceutical Co., Ltd, a leading manufacturer of nutritional supplements with certifications including cGMP, GMP, ISO, and HACCP. The Prince Pharmaceutical also provides Original Equipment Manufacturing (OEM)/Original Design Manufacturing (ODM) services for a wide array of tablet shapes, and post-processing techniques such as film coating and sugar coating.
Sponsors
Shin Kong Wu Ho-Su Memorial Hospital
National Taiwan University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥20 years old * ESRD under chronic, maintenance hemodialysis with stable dry weight for the past 6 months * Documented left ventricular ejection fraction \<50% by any imaging modality within 1 month of screening
Exclusion criteria
* Age \<20 years old * Ongoing pregnancy * NYHA class IV heart failure * Any hospitalization for heart failure within the past month * Ongoing acute urinary tract infection at the time of screening * Known acute genital infection * Severe peripheral artery disease (Rutherford category 4-6) * Acute coronary syndrome, stroke or transient ischemic attack within the past month * Recent initiation of chronic maintenance hemodialysis within 6 months * Adjustment of dry weight with changes greater than 5% of body weight within the past month * Documented left ventricular ejection fraction ≥50% by any imaging modality within 1 month of screening * Refused informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Left ventricular mass | 24 weeks of treatment | As assessed by cardiac magnetic resonance imaging, performed on non-dialysis day |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LV end-systolic volume index | 24 weeks of treatment | As assessed by cardiac magnetic resonance imaging, performed on non-dialysis day |
| LV end-diastolic volume index | 24 weeks of treatment | As assessed by cardiac magnetic resonance imaging, performed on non-dialysis day |
| LA volume index | 24 weeks of treatment | As assessed by cardiac magnetic resonance imaging, performed on non-dialysis day |
| LV ejection fraction | 24 weeks of treatment | As assessed by cardiac magnetic resonance imaging, performed on non-dialysis day |
| Global longitudinal strain | 24 weeks of treatment | As assessed by cardiac magnetic resonance imaging, performed on non-dialysis day |
| LV relative wall thickness | 12 weeks and 24 weeks of treatment | As assessed by echocardiography, performed on non-dialysis day |
| Mitral early (E) and late (A) diastolic filling velocity ratio (E/A) | 12 weeks and 24 weeks of treatment | As assessed by echocardiography, performed on non-dialysis day |
| Mitral inflow deceleration time | 12 weeks and 24 weeks of treatment | As assessed by echocardiography, performed on non-dialysis day |
| Tricuspid regurgitation peak gradient (TRPG) | 12 weeks and 24 weeks of treatment | As assessed by echocardiography, performed on non-dialysis day |
| NT-proBNP | 4 weeks, 12 weeks and 24 weeks of treatment | Blood tests obtained pre-dialysis session |
| HbA1c | 4 weeks, 12 weeks and 24 weeks of treatment | Blood tests obtained pre-dialysis session |
| Lipid profile | 4 weeks, 12 weeks and 24 weeks of treatment | Blood tests obtained pre-dialysis session |
| Left ventricular mass index | 24 weeks of treatment | As assessed by cardiac magnetic resonance imaging, performed on non-dialysis day |
| 6-minute walking distance | 12 weeks and 24 weeks of treatment | Performed on non-dialysis day |
| 3-minute heart rate variability | 12 weeks and 24 weeks of treatment | During hemodialysis session |
| Blood pressure | 12 weeks and 24 weeks of treatment | Obtained pre-dialysis session |
| Major adverse cardiovascular events (composite of CV death, myocardial infarction, stroke) | 24 weeks of treatment | By medical record confirmation and by interview |
| Lower extremity non-traumatic amputation or revascularization | 24 weeks of treatment | By medical record confirmation and by interview |
| All-cause mortality | 24 weeks of treatment | By medical record confirmation and by interview |
| Hospitalization for heart failure | 24 weeks of treatment | By medical record confirmation and by interview |
| Hypoglycemic events | 24 weeks of treatment | By medical record confirmation and by interview |
| Hypokalemia | 4 weeks, 12 weeks and 24 weeks of treatment | Blood tests obtained pre-dialysis session |
| Diabetic ketoacidosis | 24 weeks of treatment | By medical record confirmation and by interview |
| Urinary tract infection | 24 weeks of treatment | By medical record confirmation and by interview |
| Genital tract infection | 24 weeks of treatment | By medical record confirmation and by interview |
| KCCQ-OS | 12 weeks and 24 weeks of treatment | Performed on non-dialysis day |
Countries
Taiwan
Contacts
Primary ContactDonna Shu-Han Lin, MD
Backup ContactHao-Yun Lo, MD
Outcome results
None listed