DApagliflozin Cardiovascular Effects on Patients at End-stage REnal Disease (Dare-Esrd)

Dapagliflozin Cardiovascular Effects on Patients at End-stage Renal Disease

Treatment with sodium glucose co-transporter type 2 inhibitors (Sglt2i) reduced the incidence of cardiovascular death and hospitalization for heart failure by 29% in individuals with moderate chronic kidney disease. Recent observations found that beyond its effect on natriuresis, Sglt2i directly interacts with cardiomyocytes inducing improvement of myocardial function. This effect is not mitigated as glomerular filtration rate declines. Therefore, plausibly treatment with Sglt2i may attenuate heart failure in individuals end-stage kidney disease (ESKD) requiring dialysis, in whom cardiovascular disease remains the leading cause of death.

In this context, this project was designed to estimate the effect of dapagliflozin on myocardial function of dialysis subjects. Individuals with diagnosed ESKD on dialysis for at least 3 months, from both sexes, aged more than 18 years of age are eligible. Exclusion criteria are pregnant woman, hepatic failure, and known allergy to study medications. Eligible patients will be recruited from the Nephrology Division of the Clinics Hospital of the University of Campinas (Unicamp). The study was designed as a prospective, randomized, open-label, phase 4 clinical trial. Patients will be randomized, 1:1, for a 6-months treatment with either dapagliflozin 10mg/day (n=40) add to standard treatment or standard treatment alone (n=40). At the randomization visit, all patients will undergo a detailed interview and medical examination by the physician-researcher, echocardiogram and blood samples will be collected for further biochemical analysis and follow up visits will be scheduled every month for endpoints disclosure and medications dispensation until the end of study participation at the 6th month visit when echocardiogram and blood sample collection will be repeated.

Primary goal will be the difference between groups in mean change of NTproBNP levels during treatment. Secondary endpoints encompass the mean change in ejection fraction, e/e' ratio, global longitudinal and radial strain and indexed left ventricle mass. Changes in bone metabolsm and structure, assessed by serum levels of FGF-23 and α-Klotho, and changes in bone mineral density will be compared between groups as an exploratory analysis.

Study Overview

• Status: Recruiting
• Conditions: End-stage Kidney Disease
• Intervention / Treatment: Drug: Dapagliflozin

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Joaquim Barreto, MD; Phone Number: +55 19 3521 7959; Email: joaquimbarretoantunes@gmail.com

Study Locations

• Brazil
  • SP
    • Campinas, SP, Brazil, 13083610
      • Recruiting
      • Centro de Pesquisas Clinicas
      • Contact: joaquim b oliveira, md; Phone Number: +55 19 35217959

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years or older
• On regular dialysis regimen for at least 3 months

Exclusion Criteria:

• Known allergy to any of the investigational drug components
• Current use of sodium-glucose co-transporter 2 inhibitors
• Pregnant woman
• Myocardial infarction or myocardial revascularization in the past 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin; Dapagliflozin 10mg P.O. daily for 6 months add-on to standard treatment	Drug: Dapagliflozin; Dapagliflozin 10mg P.O. daily
No Intervention: Control; No intervention. Patients will be followed for 6 months on their standard treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NT-proBNP	Difference between groups in NT-proBNP change from baseline	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Echocardiography	Difference between groups from baseline of the following: ejection fraction, e/e' ratio, global longitudinal and radial strain and indexed left ventricle mass	6 months

Collaborators and Investigators

• Sponsor: University of Campinas, Brazil

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: January 5, 2023
• First Submitted That Met QC Criteria: January 5, 2023
• First Posted (Actual): January 17, 2023

Study Record Updates

• Last Update Posted (Actual): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Kidney Failure, Chronic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: 30 (AIFA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Unidentified data may be shared on reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No