A Multicenter Randomized Clinical Trial of Dapagliflozin in Patients Receiving Chronic Dialysis (The DARE-ESKD-2 Trial)

Introduction Dapagliflozin reduces heart failure (HF) incidence and hospitalizations in chronic kidney disease (CKD), but its efficacy and safety in patients on maintenance dialysis remain uncertain. Methods In this prospective, randomized, open-label, blinded end point trial performed at 3 dialysis clinics between January 2023 and September 2024, adults on chronic dialysis were randomized to once daily dapagliflozin 10 mg or standard care for 24 weeks. The primary end point was change in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Secondary end points included changes in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores and 6-minute walk test distance (6MWTD). Exploratory analysis examined intergroup differences in echocardiographic measurements and laboratory tests. Safety analysis comprised adverse event rates. Results Of 110 screened individuals, 80 were consecutively assigned (mean age: 56 years; 54% male). The median (95% confidence interval [CI]) adjusted change in NT-proBNP was 13 (−64 to 281) pg/ml in the control group and −109 (−356 to 55) pg/ml in the dapagliflozin group. The intergroup difference in NT-proBNP change was not statistically significant after adjustment by baseline values (median [95% CI] difference: −155 [−327 to −33] pg/ml; P = 0.065). No difference was found between study arms regarding the least mean (95% CI) square difference (LSD) in KCCQ clinical summary score (7 points; P = 0.073), total summary score (7 points; P = 0.094), or 6MWTD (−0.9 m; P = 0.956). Dapagliflozin did not increase the proportion of patients with improvement in 6MWTD (34.5% vs. 40.0%; odds ratio [OR]: 1.27 [95% CI: 0.44–3.74]; P = 0.657) or KCCQ clinical summary score (18.8% vs. 22.9%; OR: 1.63 [95% CI: 0.33–9.12]; P = 0.548). No difference was found between study arms regarding echocardiographic measurements or safety end points. Conclusion Dapagliflozin was safe but did not affect surrogate markers of HF compared with standard care in patients receiving maintenance dialysis, suggesting no demonstrable cardiovascular benefit over 24 weeks in this population.