Fluid management of acute decompensated heart failure subjects treated with reprieve decongestion management system

Abstract Background Achieving effective decongestion remains a critical challenge in acute decompensated heart failure (ADHF) in the EU, with 20% of patients failing to lose weight and 50% exhibiting residual congestion at discharge and worsening renal function, which can impact compliance with ESC GDMT. Barriers include suboptimal diuretic dosing, resistance, and renal dysfunction. The Reprieve System addresses these limitations by integrating real-time urine output (UO) and sodium (UNa) monitoring with automated, personalized intravenous furosemide titration and saline replacement aiming to optimize decongestion while preserving renal function, which has the potential to improve GDMT adherence. Purpose To evaluate the efficacy and safety of the Reprieve System compared to optimal diuretic therapy (ODT) in patients hospitalized with ADHF and significant volume overload. Methods The FASTR trial was a randomized, open-label pilot/ trial. A total of 100 patients admitted with AHF with ≥4.5 kg of estimated volume overload were randomized 1:1 to the Reprieve System (n=56) or to a control strategy (n=44) of optimal diuretic treatment (ODT) based on best practices of diuretic dosing from recent randomized trials. The Reprieve System initiated treatment with a furosemide dose finding phase (max 200 mg) guided by real-time UO, followed by continuous infusion. Urine output was monitored minute-by-minute via a urinary collection system. The Reprieve System provided IV saline replacement to prevent activation of renal sodium retaining mechanisms, with the saline replacement rate adjusted based on the sodium output rate. The primary efficacy endpoint was 24-hour net sodium excretion. Primary safety composite included KDIGO stage ≥2 acute kidney injury (AKI), severe electrolyte abnormalities (K3.0, Mg1.3, Na135 mEq/L), symptomatic hypotension, or hypertensive emergency. Results The Reprieve group demonstrated superior normalized 24-hour net sodium excretion (587 ± 303 vs. 436 ± 317 mmol/24h; p0.001), total urine output (9.4 ± 3.6 vs. 4.5 ± 2.8 L/24h; p0.001), and weight loss (3.8 ± 1.8 vs. 2.7 ± 2.8 kg/24h; p=0.002) versus ODT. The Reprieve group had a shorter mean therapy duration (41.7 ± 19.2 vs. 55.8 ± 21.5 hours; p0.001) and a higher percentage of patients completed IV diuresis by 72 hours (71% vs. 41%; p=0.003). Reprieve showed an acceptable safety profile with numerically lower primary safety adverse event rate. At 90 days, Reprieve also showed a numerical signal of reduced incidence of mortality and hospital readmissions (HR 0.64; 95% CI 0.31–1.3; p=0.24). Conclusion In AHF patients, the Reprieve System, compared to ODT, resulted in faster and more favorable effects on sodium output, urine output, and weight loss. Additionally, it preserved kidney function with no apparent safety signals and a trend toward a clinical benefit. These findings support an evaluation in the pivotal FASTR II trial beginning this year in both the EU and US.