TACTIC-HF: Sequential Diuretic Strategies in Ambulatory Worsening Heart Failure

Overview

TACTIC-HF is a prospective randomized crossover trial designed to compare three ambulatory diuretic strategies in patients with worsening heart failure treated in a specialized heart failure day-hospital program. Participants will receive sequential treatment with: 1. intravenous furosemide alone, 2. intravenous furosemide combined with oral acetazolamide, and 3. intravenous furosemide combined with oral hydrochlorothiazide. The primary objective is to compare short-term natriuretic response between strategies. Secondary objectives include assessment of urine output, congestion parameters, and renal/electrolyte safety. Each participant will undergo repeated outpatient treatment sessions separated by washout periods, with standardized clinical and laboratory monitoring performed during each visit. The study aims to evaluate pragmatic and clinically applicable ambulatory decongestion strategies using approved therapies commonly available in real-world practice.

Heart failure congestion remains one of the leading causes of hospitalization and recurrent healthcare utilization worldwide. Although loop diuretics represent the cornerstone of decongestive therapy, many patients develop suboptimal diuretic response or diuretic resistance during the course of chronic heart failure. Sequential nephron blockade strategies combining loop diuretics with agents acting at different tubular sites may enhance natriuresis and improve decongestion. Recent inpatient studies have suggested potential benefits of acetazolamide- and thiazide-based strategies; however, evidence regarding ambulatory worsening heart failure management remains limited. TACTIC-HF is a prospective, single-center, randomized, open-label crossover trial evaluating three commonly used outpatient decongestion strategies in patients with worsening heart failure treated in a dedicated heart failure day-hospital setting. Participants will sequentially receive: * intravenous furosemide alone, * intravenous furosemide plus oral acetazolamide, * intravenous furosemide plus oral hydrochlorothiazide. Treatments will be administered during structured outpatient sessions with standardized monitoring and predefined washout intervals between treatment periods. The primary endpoint is total urinary sodium excretion during the treatment session. Secondary endpoints include urine output, congestion-related parameters, and renal/electrolyte safety outcomes. The study is designed as a pragmatic trial using approved therapies routinely available in clinical practice, with the objective of generating physiologically oriented evidence applicable to ambulatory heart failure care.