Ca-125 versus nt-probnp guided decongestion compared with standard care in hospitalized patients with acute heart failure: rationale and design of the (COMPARE-HF) trial

Objectives

The primary objective of the COMPARE-HF trial is to evaluate whether biomarker-guided decongestion strategies improve clinical outcomes compared with standard care in patients hospitalized with acute heart failure (AHF). The study further aims to directly compare CA125-guided and NT-proBNP-guided decongestion strategies and to determine whether CA125-guided decongestion provides incremental benefit over NT-proBNP-guided and clinically guided management.

Materials and Methods

COMPARE-HF is a prospective, multicenter, open-label, randomized controlled trial. Approximately 360±60 adult patients hospitalized with AHF requiring intravenous diuretic therapy will be enrolled and randomized in a 1:1:1 ratio to CA125-guided decongestion, NT-proBNP-guided decongestion, or standard care. Patients across all left ventricular ejection fraction phenotypes (HFrEF, HFmrEF, and HFpEF) will be eligible.

In the CA125-guided arm, serial CA125 measurements will guide diuretic dose adjustments and optimization of guideline-directed medical therapy (GDMT), targeting a ≥20% reduction from baseline for CA125 <100 U/mL or a ≥30% reduction for CA125 ≥100 U/mL. In the NT-proBNP-guided arm, treatment will be guided by serial NT-proBNP measurements, targeting a ≥30% reduction or achievement of age-adjusted normal thresholds. In the standard care arm, treatment decisions will rely exclusively on clinical assessment, with biomarker results concealed from treating physicians. Patients will be followed for 12 months. The primary endpoint is a composite of all-cause mortality or rehospitalization for AHF at 12 months.

Results

The COMPARE-HF trial is designed to assess whether biomarker-guided decongestion strategies result in improved clinical outcomes compared with standard care. The study will evaluate differences among treatment arms in mortality, heart failure rehospitalizations, recurrent events, biomarker trajectories, and renal and electrolyte outcomes. Comparative analyses between CA125-guided and NT-proBNP-guided strategies will provide insight into whether targeting systemic congestion and inflammation offers incremental benefit over myocardial wall stress–guided management.

Conclusion

COMPARE-HF is the first randomized controlled trial to directly compare CA125-guided and NT-proBNP-guided decongestion strategies and to evaluate both approaches against standard clinically guided care in patients hospitalized with acute heart failure. By addressing residual congestion through biomarker-guided treatment algorithms, this study aims to generate robust evidence to inform personalized decongestion strategies and improve outcomes in acute heart failure.figureFor image description, please refer to the figure legend and surrounding text.