Cardiovascular Effects of SGLT2 Inhibitors in Hemodialysis Patients: A Phase 2 Randomized Study
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-70
SponsorMaximo Agustin Schiavone
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
Current immunosuppressive therapy
Contraindication to cardiac MRI
Known hypersensitivity or intolerance to SGLT2 inhibitors
Participation in another interventional clinical trial
Trial design
Design model
Parallel
Treatments tested in this trial
iSGLT2
DrugParticipants randomized to the experimental arm will receive a once-daily dose of a sodium-glucose cotransporter 2 inhibitor (SGLT2i), administered orally, in addition to their standard hemodialysis care. The specific agent (e.g., dapagliflozin or empagliflozin) and dose will be selected based on safety data and clinical guidelines applicable to patients with end-stage renal disease (ESRD) on dialysis. The intervention will be maintained for 12 months. Dosing will be monitored by the research team to ensure tolerability and adherence. All patients in the experimental group will undergo comprehensive cardiovascular assessment, including serial cardiac MRI, echocardiography, and measurement of fibrosis-related biomarkers. This intervention differs from standard care by introducing a pharmacologic agent not routinely administered in the dialysis population, targeting cardiac remodeling, fibrosis, and intradialytic complications.
Treatment groups
80 Participants
are divided into 2 treatment groupsGroup A: ControlNo intervention 0 interventions
Group B: Drug: iSGLT2Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Change in Left Ventricular Mass Index (LVMI)
LVMI will be measured using cardiac MRI and/or echocardiography at baseline, and at months 3, 6, and 12. The primary outcome will be the change (Δ) in LVMI compared to baseline. Reductions in LVMI will be interpreted as a marker of reverse remodeling and reduced fibrosis.
Time frame
Baseline, Month 3, Month 6, and Month 122
Change in Left Ventricular Ejection Fraction (LVEF)
LVEF will be measured by echocardiography at baseline and at months 3, 6, and 12. The primary outcome will be the change from baseline. Improvements will indicate enhancement in global systolic function.
Time frame
Baseline, Month 3, Month 6, Month 123
Change in Myocardial Fibrosis as Assessed by Cardiac MRI
Cardiac MRI with T1/T2 mapping will be performed at baseline, and at months 3, 6, and 12. Quantitative measures of myocardial fibrosis will be compared to baseline to assess changes over time.
Time frame
Baseline, Month 3, Month 6, Month 124
Change in Pro-fibrotic Biomarkers (FGF23, Procollagen I and III)
Blood levels of FGF23, procollagen type I, and procollagen type III will be measured at baseline and months 3, 6, and 12. The outcome is defined as the change from baseline. These biomarkers reflect myocardial fibrosis activity.
Time frame
Baseline, Month 3, Month 6, Month 12Secondary outcomes
1
Major Adverse Cardiovascular Events (MACE)
Includes new or worsening heart failure, confirmed myocardial infarction, stroke, or clinically significant arrhythmia. Events will be adjudicated based on clinical criteria.
Time frame
Baseline through Month 122
Cardiovascular Mortality
Deaths due to cardiovascular causes, including sudden cardiac death, will be recorded and classified according to investigator assessment and clinical documentation.
Time frame
Baseline through Month 123
All-Cause Mortality
All deaths occurring during the study period will be recorded regardless of cause. Attribution (cardiac, non-cardiac, unknown) will be documented when possible.
Time frame
Baseline through Month 124
Cause-Specific Hospitalizations
Hospitalizations will be recorded and categorized as cardiovascular, infectious, AV-fistula-related, or other. Events will be assessed from enrollment through study completion.
Time frame
Baseline through Month 12Locations
1Map coordinates are unavailable for these locations. Locations are shown below instead.
Fresenius Medical Care - CEMIC SaavedraRecruitingC1431FWO, Buenos Aires, Buenos Aires
Argentina
ArgentinaSponsors and contacts
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Maximo Agustin Schiavone
Lead sponsor
Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno
Sponsor institution
Source ClinicalTrials.gov