Cardiovascular Effects of SGLT2 Inhibitors in Hemodialysis Patients: A Phase 2 Randomized Study

NCT ID: NCT06929169

Last Updated: 2025-04-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-31
• Study Completion Date: 2026-08-31

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.

Conditions

Chronic Kidney Disease Requiring Hemodialysis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control

Participants in this arm will continue receiving standard hemodialysis treatment, including all routine medical care, medications, and monitoring as per institutional protocols. They will not receive an SGLT2 inhibitor.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Drug: iSGLT2

Participants in this arm will receive a sodium-glucose cotransporter 2 inhibitor (SGLT2i) once daily by oral administration, in addition to standard hemodialysis care. The specific agent (e.g., dapagliflozin or empagliflozin) and dose will be selected based on safety data and existing recommendations for patients with end-stage renal disease on dialysis. The intervention will be administered for 12 months. Participants will undergo cardiovascular monitoring, including cardiac MRI, echocardiography, and biomarker assessment at baseline, and months 3, 6, and 12. This arm is designed to evaluate the effects of SGLT2 inhibition on cardiac function, myocardial fibrosis, and intradialytic hypotension.

Group Type: EXPERIMENTAL

iSGLT2

Intervention Type: DRUG

Participants 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.

Interventions

iSGLT2

Participants 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.

Intervention Type: DRUG

Other Intervention Names

SGLT2 inhibitor

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maximo Agustin Schiavone

OTHER

Sponsor Role: lead

Responsible Party

Maximo Agustin Schiavone

Principal Investigator and Sponsor-Investigator, CEMIC

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Carlos E Castellaro, MD, MSc

Role: STUDY_DIRECTOR

Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno

Locations

Fresenius Medical Care - CEMIC Saavedra

Buenos Aires, Buenos Aires, Argentina

Site Status: RECRUITING

Countries

Argentina

Central Contacts

Maximo A Schiavone, MD, MSc

Role: CONTACT

maximoschiavone@gmail.com

+5491138093510

Facility Contacts

Maximo A, Schiavone, MD

Role: primary

maximoschiavone@gmail.com

+5491138093510

Carlos E. Castellaro, MD

Role: backup

cecastellaro@cemic.edu.ar

Other Identifiers

PRIISA BA: 8767

Identifier Type: -

Identifier Source: org_study_id