Mechanisms of Diuretic Resistance in Heart Failure, Aim 3

Recruiting · NCT06209359 · Interventional (participants receive a specific treatment) · Lead sponsor: Yale University

Interventions studied

Ammonium ChloridePlacebo

Randomized double-blind placebo-controlled crossover study design

Age range

18 Years and older

Sex

All (male and female)

Healthy volunteers

No - a diagnosis or condition is required

Phase

Phase 1

Study type

Interventional (participants receive a specific treatment)

Clinical diagnosis of heart failure
No plan for titration/change of heart failure medical or device therapies during the study period.
Absence of non-elective hospitalizations in the previous 2 months.
At optimal volume status by symptoms, exam, and dry weight.
Serum potassium ≤ 5.0 mmol/L
Serum sodium ≥ 130 milliequivalents/ liter (mEq/L)
Hemoglobin ≥8 g/dL
Age \>18 years
Objective evidence of diuretic resistance to a 10mg bumetanide challenge (screening visit may occur under this protocol or HIC2000032328 or HIC2000034315) defined as:
FENa \<10% and total sodium output \<150mmol
And at least one of the following criteria:
Chronic home furosemide dose greater than or equal to 80mg furosemide equivalents
eGFR \< 60ml/min
Serum chloride \<100mmol/L
FENa \<5% and total sodium output \<75mmol on the 2 hour

Glomerular filtration rate (GFR) \<20 ml/min/1.73m2
Use of any non-loop type diuretic in the last 7 days with the exclusion of low dose aldosterone antagonist (e.g., spironolactone ≤50 mg)
History of flash pulmonary edema or a "brittle" volume sensitive HF phenotype such as amyloid cardiomyopathy
Hemoglobin \< 8 g/dL
Pregnant or breastfeeding
Cirrhosis or known liver disease
History of metabolic or respiratory acidosis within 30 days
Use of metformin, acetazolamide, or any other agent that could predispose to acidosis
Patients who are on metformin may be enrolled if their metformin can be safely discontinued for the randomized treatment periods in each arm. Any participants who have consistently elevated blood glucose readings \> 200 mg/dL while inpatient will not be enrolled.
Serum bicarbonate level \<24mmol/L at screening visit
Venous potential of hydrogen(pH) \<7.35 at screening visit
Inability to give written informed consent or comply with study protocol or follow-up visits
On Lithium therapy
On pimozide or thioridazine
Diagnosis of liver failure
Contraindications or allergy to sulfonamides
Any contraindication to thiazide diuretic or allergy to thiazide or bendroflumethiazide

1 location listed across 1 US state.