RANDOMIZED CLINICAL TRIAL, PHASE 4, ON THE CARDIOVASCULAR EFFECT OF DAPAGLIFLOZIN IN PATIENTS IN END-STAGE KIDNEY DISEASE UNDER DIALYTIC TREATMENT: DARE-ESRD-BHS-4

• Grant number: 23/16961-1
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2025
• End date: March 31, 2027
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Andrei Carvalho Sposito
• Grantee: Andrei Carvalho Sposito
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Maria Eugênia Fernandes Canziani

Abstract

The use of Sglt2 inhibitors (Sglt2i) in patients with moderate chronic kidney disease (CKD) demonstrated a reduction of up to 29% in the incidence of cardiovascular death and hospitalization for heart failure (HF). In addition to the effect of this class on natriuresis, experimental data suggest the action of Sglt2i directly on the myocardium. This cardiovascular benefit does not attenuate and even tends to increase as the glomerular filtration rate reduces. Therefore, it is possible that, at least in part, treatment with Sglt2i may also attenuate HF in dialysis patients, in whom the manifestation of HF is intensified and the natriuresis mechanism is mitigated. In this context, this project proposes to investigate the effects of dapagliflozin on the myocardial function of dialysis patients in a randomized phase 4 clinical trial. To date, 60 patients have been randomized, and the study is ongoing. A total of 80 patients will be recruited from the dialysis clinic of the Nephrology Service of the UNICAMP Hospital de Clínicas. These patients will be randomized to 24-week treatment with dapagliflozin, while the control group will receive standard treatment without the addition of Sglt2i. Participants will undergo clinical-laboratory evaluation, electrocardiogram, 3D echocardiography, 6-minute walk test and dual-energy X-ray absorptiometry. The primary outcome will be the difference in the mean variation in plasma NT-proBNP values between the control and dapagliflozin groups. Secondary outcomes will include echocardiographic variables of systolic and diastolic function, plasma levels of nitrite, nitrate and asymmetric dimethylarginine, body composition and RR interval variability on electrocardiogram. (AU)