RecruitingPhase 1NCT05323487

Mechanisms of Diuretic Resistance in Heart Failure, Aim 1

Mechanisms of Diuretic Resistance in Heart Failure

Sponsor

Yale University

Enrollment

75 participants

Start Date

Jun 1, 2022

Study Type

INTERVENTIONAL

Conditions

Heart Failure

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 75 heart failure (HF) patients.

Eligibility

Min Age: 18 Years

Inclusion Criteria5

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

Exclusion Criteria7

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

Interventions

DRUGBumetanide Injection

Participants in balance will present to the study site Day 0 and receive their first randomized dose of bumetanide (1.25mg, 2.5mg, 5mg, or 10mg) and undergo the bio-specimen collection protocol. They will return every 3 days, allowing 2 full days washout, to receive the other doses in random sequence.