Clinical trial NCT06249932: Empagliflozin in Heart Failure with Reduced Ejection Fraction and End Stage Renal Disease
Official title: The Safety and Efficacy of Empagliflozin in Patients with End-stage Renal Disease and Heart Failure with Reduced Ejection Fraction - a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Heart Failure with Reduced Ejection Fraction
End Stage Renal Disease on Dialysis
Keywords: end stage renal disease
sodium-glucose co-transporter 2 inhibitors,
heart failure with reduced ejection fraction
empagliflozin
left ventricular mass
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
Collaborators: name: Shin Kong Wu Ho-Su Memorial Hospital
First posted: 2024-02-08
Enrollment: 95
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Left ventricular mass
timeFrame: 24 weeks of treatment
Secondary outcomes:
measure: Left ventricular mass index
timeFrame: 24 weeks of treatment
measure: LV end-systolic volume index
timeFrame: 24 weeks of treatment
measure: LV end-diastolic volume index
timeFrame: 24 weeks of treatment
measure: LA volume index
timeFrame: 24 weeks of treatment
measure: LV ejection fraction
timeFrame: 24 weeks of treatment
measure: Global longitudinal strain
timeFrame: 24 weeks of treatment
measure: LV end-systolic volume index
timeFrame: 12 weeks and 24 weeks of treatment
measure: LV end-diastolic volume index
timeFrame: 12 weeks and 24 weeks of treatment
measure: LA volume index
timeFrame: 12 weeks and 24 weeks of treatment
measure: LV ejection fraction
timeFrame: 12 weeks and 24 weeks of treatment
measure: Left ventricular mass index
timeFrame: 12 weeks and 24 weeks of treatment
measure: Global longitudinal strain
timeFrame: 12 weeks and 24 weeks of treatment
measure: LV relative wall thickness
timeFrame: 12 weeks and 24 weeks of treatment
measure: Mitral early (E) and late (A) diastolic filling velocity ratio (E/A)
timeFrame: 12 weeks and 24 weeks of treatment
measure: Mitral inflow deceleration time
timeFrame: 12 weeks and 24 weeks of treatment
measure: Tricuspid regurgitation peak gradient (TRPG)
timeFrame: 12 weeks and 24 weeks of treatment
measure: NT-proBNP
timeFrame: 4 weeks, 12 weeks and 24 weeks of treatment
measure: HbA1c
timeFrame: 4 weeks, 12 weeks and 24 weeks of treatment
measure: Lipid profile
timeFrame: 4 weeks, 12 weeks and 24 weeks of treatment
measure: KCCQ-OS
timeFrame: 12 weeks and 24 weeks of treatment
measure: 6-minute walking distance
timeFrame: 12 weeks and 24 weeks of treatment
measure: 3-minute heart rate variability
timeFrame: 12 weeks and 24 weeks of treatment
measure: Blood pressure
timeFrame: 12 weeks and 24 weeks of treatment
measure: Major adverse cardiovascular events (composite of CV death, myocardial infarction, stroke)
timeFrame: 24 weeks of treatment
measure: Lower extremity non-traumatic amputation or revascularization
timeFrame: 24 weeks of treatment
measure: All-cause mortality
timeFrame: 24 weeks of treatment
measure: Hospitalization for heart failure
timeFrame: 24 weeks of treatment
measure: Hypoglycemic events
timeFrame: 24 weeks of treatment
measure: Hypokalemia
timeFrame: 4 weeks, 12 weeks and 24 weeks of treatment
measure: Diabetic ketoacidosis
timeFrame: 24 weeks of treatment
measure: Urinary tract infection
timeFrame: 24 weeks of treatment
measure: Genital tract infection
timeFrame: 24 weeks of treatment
Other outcomes:
Locations:
city: Hsinchu City
country: Taiwan
facility: National Taiwan University Hospital Hsinchu Branch
city: Taipei
country: Taiwan
facility: Shin Kong Wu Ho-Su Memorial Hospital
Study officials:
affiliation: Shin Kong Wu Ho-Su Memorial Hospital
name: Donna Shu-Han Lin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University Hsin-Chu Hospital
name: Chih-Cheng Wu, MD. PhD
role: PRINCIPAL_INVESTIGATOR
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