Clinical trial NCT06929169: Cardiovascular Effects of SGLT2 Inhibitors in Hemodialysis Patients: A Phase 2 Randomized Study
Official title: Cardiovascular Effects of SGLT2 Inhibitors in Hemodialysis Patients: A Phase 2 Randomized Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Kidney Disease Requiring Hemodialysis
Keywords: SGLT2 Inhibitors
Hemodialysis
Cardiac MRI
Ventricular Remodeling
Heart Failure with Preserved Ejection Fraction
Myocardial Fibrosis
Cardiovascular Disease
Chronic Kidney Disease
Lead sponsor: Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno
Sponsor class: OTHER
First posted: 2025-04-16
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients with end-stage kidney disease (ESKD) on hemodialysis face an unacceptably high rate of cardiovascular complications, including heart failure, arrhythmias, and sudden cardiac death. Many of these outcomes are driven by diastolic dysfunction and cardiac fibrosis-conditions that are not adequately addressed by current therapies. SGLT2 inhibitors, originally developed for the treatment of type 2 diabetes, have demonstrated cardiovascular and renal protective effects across multiple patient populations, independent of glycemic control.

This Phase 2, randomized, controlled clinical trial will evaluate the safety and efficacy of SGLT2 inhibitors in patients undergoing maintenance hemodialysis. A total of 80 participants will be randomized to receive either an SGLT2 inhibitor or standard care for 12 months. The primary objective is to determine whether SGLT2 inhibitors improve cardiac function, reduce myocardial fibrosis, and decrease the incidence of intradialytic hypotension. Secondary endpoints include cardiovascular events, hospitalization, and all-cause mortality. The study will also assess changes in key biomarkers and perform advanced cardiac imaging to evaluate structural and functional outcomes.

This trial represents a novel and timely investigation into a class of medications with promising pleiotropic effects, potentially offering new therapeutic options for a high-risk, underserved population.

Detailed description: This is a Phase 2, prospective, randomized, open-label, controlled study designed to assess the safety and efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis. Despite advances in renal replacement therapy, cardiovascular mortality remains the leading cause of death in this population, often due to heart failure with preserved ejection fraction (HFpEF), arrhythmic events, and myocardial fibrosis. Preclinical models and clinical data in non-dialysis populations suggest that SGLT2 inhibitors exert antifibrotic, anti-inflammatory, and mitochondrial-stabilizing effects that may ameliorate these pathophysiological processes.

A total of 80 eligible patients, aged 18-70 years and receiving online hemodiafiltration for at least 3 months, will be enrolled at Fresenius Medical Center - CEMIC Saavedra (Buenos Aires, Argentina). Participants will be randomized into two parallel groups (intervention vs. control) stratified by age, sex, and dialysis vintage. The intervention group will receive a once-daily SGLT2 inhibitor, while the control group will continue standard care.

Primary outcomes include the incidence and severity of intradialytic hypotension (defined by KDOQI 2020 and HEMO criteria), longitudinal changes in left ventricular mass index (LVMI), ejection fraction, myocardial fibrosis as assessed by cardiac MRI (T1/T2 mapping), and circulating pro-fibrotic biomarkers (e.g., FGF23, procollagen types I and III). Secondary endpoints include major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, and cause-specific hospitalizations.

Comprehensive phenotyping will be conducted at baseline, months 3, 6, and 12. Assessments include echocardiography, cardiac MRI, 24-hour Holter monitoring, impedance cardiography, pulse wave velocity measurement, and detailed laboratory profiling. Data will be analyzed using appropriate parametric and non-parametric statistical tests, with multivariate regression and survival analysis techniques applied where relevant.

The study complies with ICH-GCP guidelines and the Declaration of Helsinki. The CEMIC institutional review board has granted ethical approval. Informed consent will be obtained from all participants prior to enrollment. The study is funded by institutional and investigator resources, with biomarker assays supported by the lead investigator through his research affiliations with CEMIC and Charité -Universitätsmedizin Berlin.

This study aims to address a critical unmet need in cardio-renal medicine and may lay the groundwork for future therapeutic strategies in dialysis-dependent patients.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 and ≤70 years
* Diagnosed with end-stage renal disease
* Undergoing online hemodiafiltration for at least 3 months
* Able to provide written informed consent

Exclusion Criteria:

* Current immunosuppressive therapy
* Contraindication to cardiac MRI
* Known hypersensitivity or intolerance to SGLT2 inhibitors
* Participation in another interventional clinical trial
* History of diabetic ketoacidosis
* Active substance abuse
* Diagnosis of type 1 diabetes mellitus
* History of kidney transplantation
* Acute coronary event within 30 days before enrollment
* Current or recent treatment with an SGLT2 inhibitor

Primary outcomes:
measure: Change in Left Ventricular Mass Index (LVMI)
timeFrame: Baseline, Month 3, Month 6, and Month 12
measure: Change in Left Ventricular Ejection Fraction (LVEF)
timeFrame: Baseline, Month 3, Month 6, Month 12
measure: Change in Myocardial Fibrosis as Assessed by Cardiac MRI
timeFrame: Baseline, Month 3, Month 6, Month 12
measure: Change in Pro-fibrotic Biomarkers (FGF23, Procollagen I and III)
timeFrame: Baseline, Month 3, Month 6, Month 12
measure: Incidence of Intradialytic Hypotension
timeFrame: Baseline through Month 12
Secondary outcomes:
measure: Major Adverse Cardiovascular Events (MACE)
timeFrame: Baseline through Month 12
measure: Cardiovascular Mortality
timeFrame: Baseline through Month 12
measure: All-Cause Mortality
timeFrame: Baseline through Month 12
measure: Cause-Specific Hospitalizations
timeFrame: Baseline through Month 12
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Fresenius Medical Care - CEMIC Saavedra
Study officials:
affiliation: Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno
name: Carlos E Castellaro, MD, MSc
role: STUDY_DIRECTOR
References: