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

NCT06929169 | Recruiting Phase 2 DMC

• 1 other identifier: PRIISA BA: 8767
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (5)

• 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.

  Baseline, Month 3, Month 6, and Month 12

• 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.

  Baseline, Month 3, Month 6, Month 12

• 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.

  Baseline, Month 3, Month 6, Month 12

• 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.

  Baseline, Month 3, Month 6, Month 12

• Incidence of Intradialytic Hypotension

  Includes new or worsening heart failure, confirmed myocardial infarction, stroke, or clinically significant arrhythmia. Events will be adjudicated based on clinical criteria.

  Baseline through Month 12

Secondary Outcomes (4)

• Major Adverse Cardiovascular Events (MACE)

  Baseline through Month 12

• Cardiovascular Mortality

  Baseline through Month 12

• All-Cause Mortality

  Baseline through Month 12

• Cause-Specific Hospitalizations

  Baseline through Month 12

Study Arms (2)

Control

NO INTERVENTION

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.

Drug: iSGLT2

EXPERIMENTAL

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.

Drug: iSGLT2

Interventions

iSGLT2 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.

Also known as: SGLT2 inhibitor

Drug: iSGLT2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Maximo Agustin Schiavone: lead

Study Sites (1)

Fresenius Medical Care - CEMIC Saavedra

Buenos Aires, Buenos Aires, C1431FWO, Argentina

RECRUITING

MeSH Terms

Conditions

Ventricular Remodeling; Cardiovascular Diseases; Renal Insufficiency, Chronic

Interventions

Sodium-Glucose Transporter 2 Inhibitors

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Study Officials

• Carlos E Castellaro, MD, MSc

  Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno

  STUDY DIRECTOR

Central Study Contacts

Maximo A Schiavone, MD, MSc

CONTACT

+5491138093510; maximoschiavone@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator and Sponsor-Investigator, CEMIC

Study Record Dates

• First Submitted: April 8, 2025
• First Posted: April 16, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: April 16, 2025

Record last verified: 2025-04

Locations

AR (1)