What this Trial Is About

Researchers are investigating the mechanisms of diuretic resistance in patients with heart failure through a Phase 1 study involving 75 participants. The study aims to understand how different doses of the diuretic bumetanide affect kidney function and sodium excretion. Participants have a clinical diagnosis of heart failure and are monitored to explore the response to varying doses of the diuretic in a controlled setting. Participants will start the study by following a controlled diet with a fixed sodium intake for five days to reduce variability in diuretic response. On Day 0, participants receive their first randomized dose of bumetanide (1.25mg, 2.5mg, 5mg, or 10mg) intravenously over one hour, followed by bio-specimen collection. They return every three days for additional doses in a randomized sequence, allowing two full days washout between treatments to assess responses to different doses. Throughout the study, participants undergo assessments including measuring fractional excretion of sodium and lithium before and after bumetanide infusion, as well as evaluating kidney tubular efficiency and RNA markers in urine at baseline. The study monitors diuretic response and safety, with participants required to maintain the diet and attend follow-up visits. The total duration includes initial screening, treatment visits spaced three days apart, and bio-specimen collections to understand diuretic resistance mechanisms in heart failure.

Mechanisms of Diuretic Resistance in Heart Failure, Aim 1