DESAL-HEART: Hypertonic Saline Added to a Pre-declared Furosemide Dose in Acute Heart Failure - NCT07927127

Sponsor: University of Alberta Conditions: Acute Heart Failure (AHF), Acute Decompensated Heart Failure DESAL-HEART is a multicenter, randomized, open-label, blinded-endpoint, mechanistic proof-of-concept trial conducted within the Heart Failure Efficacy and Research Trial (HEART) Platform. The study will evaluate whether adding a single infusion of 3% hypertonic saline solution (HSS) to a pre-declared intravenous furosemide dose improves decongestion in patients hospitalized with acute heart failure. Background and Rationale Congestion is a major cause of hospitalization in patients with acute heart failure. Intravenous loop diuretics, such as furosemide, are the standard treatment for removing excess fluid, but treatment responses vary and residual congestion remains common. Hypertonic saline may temporarily increase effective circulating blood volume, improve kidney perfusion, and enhance the delivery and effectiveness of furosemide. Although previous studies have suggested potential benefits, limitations in study quality and differences in treatment regimens have prevented definitive conclusions. DESAL-HEART is designed to isolate the effect of hypertonic saline by ensuring that the furosemide dose is determined before randomization and administered in both treatment groups. Study Design A total of 60 adults hospitalized with acute heart failure and persistent congestion will be randomized in a 1:1 ratio to receive either: A single 150 mL infusion of 3% hypertonic saline administered over 30 minutes together with a pre-declared intravenous furosemide dose; or The same pre-declared intravenous furosemide dose alone. Randomization will be performed centrally using REDCap, with stratification by chronic kidney disease status. The study is open-label because the control group will not receive a placebo infusion. Laboratory endpoints will be assessed objectively. The treating clinician will determine and document the intravenous furosemide dose before randomization. Subsequent heart failure management will remain at the discretion of the treating physician. Study Objectives and Assessments The primary objective is to estimate the effect of hypertonic saline on NT-proBNP, a biomarker of heart failure, measured 24 ± 6 hours after randomization. The key mechanistic secondary endpoint is spot urine sodium concentration measured 90-150 minutes after randomization, providing an early measure of the kidneys' response to diuretic treatment. Additional assessments include: NT-proBNP at 48 ± 6 hours after randomization. Spot urine sodium from the first urine sample collected more than 6 hours after randomization. Changes in body weight, hemoglobin, hematocrit, serum electrolytes, and creatinine at 24 hours. Urine output, net fluid balance, and additional decongestive treatments during the first 24 hours. Treatment delivery, recruitment feasibility, and completeness of outcome assessments. Safety assessments will include infusion intolerance, clinically important electrolyte abnormalities, changes in kidney function, symptomatic hypotension, worsening respiratory status, and serious adverse events. A serum sodium increase of at least 5 mmol/L from baseline or any sodium value of at least 150 mmol/L is a prespecified adverse event of special interest. Exploratory outcomes include major adverse kidney events and days alive and out of hospital at 30 days. Additional clinical and patient-reported outcomes will be collected through the HEART Platform. Statistical Analysis and Study Purpose The primary analysis will use a mixed model for repeated measures to compare log-transformed NT-proBNP at 24 and 48 hours between treatment groups, adjusting for baseline NT-proBNP, site, chronic kidney disease status, age, and sex. The treatment effect will be reported as a geometric mean ratio with a 95% confidence interval. This 60-participant study is intended to estimate the magnitude and precision of the biological treatment effect rather than establish clinical efficacy. A prespecified Green/Yellow/Red decision framework will integrate the biological signal, urine sodium response, safety, and feasibility to determine whether further investigation in a definitive clinical outcomes trial is warranted.