Clinical trial NCT06249945: EMPAgliflozin in Heart Failure With PReserved 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 Preserved Ejection Fraction - a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Heart Failure With Preserved Ejection Fraction
End Stage Renal Disease on Dialysis
Keywords: end-stage renal disease
sodium-glucose co-transporter 2 inhibitors
heart failure
diastolic function
empagliflozin
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
Collaborators: name: Shin Kong Wu Ho-Su Memorial Hospital
First posted: 2024-02-08
Enrollment: 150
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: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Mitral early (E) and late (A) diastolic filling velocity ratio (E/A)
timeFrame: 24 weeks of treatment
Secondary outcomes:
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: LA strain
timeFrame: 12 weeks and 24 weeks of treatment
measure: Mitral inflow deceleration time
timeFrame: 12 weeks and 24 weeks of treatment
measure: Mitral inflow deceleration time LV relative wall thickness
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: 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
measure: Hypokalemia
timeFrame: 4 weeks, 12 weeks and 24 weeks of treatment
Other outcomes:
Locations:
city: Hsinchu
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 SH 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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