End Stage Renal Disease on Dialysis, Heart Failure With Preserved Ejection Fraction
Conditions
Keywords
end-stage renal disease, sodium-glucose co-transporter 2 inhibitors, heart failure, diastolic function, empagliflozin
Brief summary
The presence of CKD has been linked to the development of HFpEF. Currently, the treatment for HFpEF is limited. SGLT2i are one of the few drug classes that have proven efficacy in HFpEF in randomized controlled trials. The results of mechanistic studies suggest that the benefits of SGLT2i on diastolic heart failure are independent of their glycosuric actions and may still be present in anuric subjects. Despite the significance of HFpEF in patients with CKD, patients with advanced kidney disease have been excluded from studies investigating anti-heart failure drugs. The effects of SGLT2i in patients under maintenance dialysis are largely unknown. Past pharmacokinetics and pharmacodynamics studies on empagliflozin in patients with end-stage renal disease (ESRD) demonstrated that the use of empagliflozin in patients with ESRD seemed safe, 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 dialysis with stable dry weight for the past 6 months * Prior diagnosis of HFpEF, as defined by a score of ≥5 on the HFA-PEFF diagnostic algorithm.
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 =\<40% by any imaging modality within 1 month of screening * Refused informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mitral early (E) and late (A) diastolic filling velocity ratio (E/A) | 24 weeks of treatment | As assessed by echocardiography, performed on non-dialysis day |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left ventricular mass index | 12 weeks and 24 weeks of treatment | As assessed by echocardiography, performed on non-dialysis day |
| Global longitudinal strain | 12 weeks and 24 weeks of treatment | As assessed by echocardiography, performed on non-dialysis day |
| LA strain | 12 weeks and 24 weeks of treatment | As assessed by echocardiography, performed on non-dialysis day |
| LV end-systolic volume index | 12 weeks and 24 weeks of treatment | As assessed by echocardiography, performed on non-dialysis day |
| LV end-diastolic volume index | 12 weeks and 24 weeks of treatment | As assessed by echocardiography, performed on non-dialysis day |
| LA volume index | 12 weeks and 24 weeks of treatment | As assessed by echocardiography, performed on non-dialysis day |
| LV ejection fraction | 12 weeks and 24 weeks of treatment | As assessed by echocardiography, performed on non-dialysis day |
| Mitral inflow deceleration time LV relative wall thickness | 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 |
| Mitral inflow deceleration time | 12 weeks and 24 weeks of treatment | As assessed by echocardiography, 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 |
| 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 |
| Hypokalemia | 4 weeks, 12 weeks and 24 weeks of treatment | Blood tests obtained pre-dialysis session |
| KCCQ-OS | 12 weeks and 24 weeks of treatment | Performed on non-dialysis day |
Countries
Taiwan
Contacts
Primary ContactDonna SH Lin, MD
Backup ContactHao-Yun Lo, MD
Outcome results
None listed