Mechanisms of Diuretic Resistance in Heart Failure, Aim 3
Yale University
Summary
Randomized double-blind placebo-controlled crossover study design
Description
Briefly, the protocol will begin with pre-study determination of diuretic response at the screening visit via administration of 10 mg IV bumetanide and measuring peak FENa. Participants may proceed to the subsequent study procedures. Participants will begin a study diet provided by the metabolic kitchen five days prior to Day 0. Beginning on day 0, participants will take either NH4Cl or placebo 75mmol twice daily. On day 1, the participant will return to study site and receives the first dose of their twice daily study medication as well as their regular loop diuretic dose given as IV bumetani…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 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% an…
Interventions
- DrugAmmonium Chloride
Participants will be randomized to receive either ammonium chloride or placebo. Participants will receive randomized drug in combination with IV bumetanide, bendroflumethiazide, and amiloride. Following a washout period, participants will be crossed over to the alternate drug.
- DrugPlacebo
Participants will be randomized to receive either ammonium chloride or placebo. Participants will receive randomized drug in combination with IV bumetanide, bendroflumethiazide, and amiloride. Following a washout period, participants will be crossed over to the alternate drug.
Location
- Yale UniversityNew Haven, Connecticut