Empagliflozin in Heart Failure with Reduced Ejection Fraction and End Stage Renal Disease
- Conditions
- Heart Failure with Reduced Ejection FractionEnd Stage Renal Disease on Dialysis
- Interventions
- Drug: Placebo
- Registration Number
- NCT06249932
- Lead Sponsor
- National Taiwan University Hospital
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 95
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description empagliflozin Empagliflozin 25 MG Jardiance, 25 mg, QD, for 6 months placebo Placebo QD, for 6 months
- Primary Outcome Measures
Name Time Method Left ventricular mass 24 weeks of treatment As assessed by cardiac magnetic resonance imaging, performed on non-dialysis day
- Secondary Outcome Measures
Name Time Method 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
Major adverse cardiovascular events (composite of CV death, myocardial infarction, stroke) 24 weeks of treatment By medical record confirmation and by interview
Left ventricular mass index 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 ejection fraction 12 weeks and 24 weeks of treatment As assessed by echocardiography, performed on non-dialysis day
Lower extremity non-traumatic amputation or revascularization 24 weeks of treatment By medical record confirmation and by interview
LV end-diastolic volume index 12 weeks and 24 weeks of treatment As assessed by echocardiography, performed on non-dialysis day
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
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
KCCQ-OS 12 weeks and 24 weeks of treatment 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
Genital tract infection 24 weeks of treatment By medical record confirmation and by interview
LA volume 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
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
LV relative wall thickness 12 weeks and 24 weeks of treatment As assessed by echocardiography, performed on non-dialysis day
Trial Locations
- Locations (2)
National Taiwan University Hospital Hsinchu Branch
🇨🇳Hsinchu City, Taiwan
Shin Kong Wu Ho-Su Memorial Hospital
🇨🇳Taipei, Taiwan