Mechanisms of Diuretic Resistance in Heart Failure

• Status: Not yet recruiting
• Trial end date: 2026-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will employ a randomized order, double-blind, repeated measures dose ranging design. This design was chosen in order to generate multiple within-subject serial loop diuretic dose response exposures. The overall study schema will include 50 diuretic resistant HF patients and 25 diuretic responsive heart failure (HF) patients.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Yale University
• Treatments: Bumetanide

Criteria

Inclusion Criteria:

• Clinical diagnosis of HF

• No plan for titration/change of heart failure medical or device therapies during the study period.

• Absence of non-elective hospitalizations in the previous 3 months.

• At optimal volume status by symptoms, exam, and dry weight

• Age > 18 years

• Additional inclusion criteria for diuretic resistant cohort determined at the diuretic challenge visit: Peak FENa < 5% following 10mg IV bumetanide challenge

• Additional inclusion criteria for diuretic responsive cohort determined at the diuretic challenge visit: Peak FENa > 10% following 10mg IV bumetanide challenge

Exclusion Criteria:

• GFR <20 ml/min/1.73m2 using the Chronic Kidney Disease- Epidemiology (CKD-EPI)equation or use of renal replacement therapies

• Use of any non-loop type diuretic in the last 14 days with the exclusion of low dose aldosterone antagonist (e.g., spironolactone or eplerenone ≤50 mg). Examples of non-loop diuretics include but may not be limited to acetazolamide (oral or IV, not ophthalmic), metolazone, Hydrochlorothiazide (HCTZ), chlorthalidone, chlorothiazide, indapamide, triamterene, amiloride, finerenone, spironolactone dose > 50mg day, eplerenone > 50mg/day,

• History of flash pulmonary edema requiring hospitalization and treatment with biphasic positive airway pressure or mechanical ventilation or a "brittle" volume sensitive HF phenotype such as an infiltrative or restrictive cardiomyopathy (i.e. amyloid cardiomyopathy, etc).

• Hemoglobin < 8 g/dL

• Pregnant or breastfeeding

• Inability to give written informed consent or comply with study protocol or follow-up visits

• Chronic Urinary retention limiting ability to perform timed urine collection procedures