Mechanisms of Diuretic Resistance in Heart Failure, Aim 2
Trial Parameters
Brief Summary
Randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide.
Eligibility Criteria
Inclusion Criteria: 1. Clinical diagnosis of HF 2. No plan for titration/change of heart failure medical or device therapies during the study period. 3. Absence of non-elective hospitalizations in the previous 2 weeks 4. At optimal volume status by symptoms, exam, and dry weight. 5. Serum potassium ≤ 5.0 mmol/L 6. Serum sodium ≥ 130 mEq/L 7. Age \> 18 years 8. Hemoglobin ≥8 g/dL 9. Objective evidence of diuretic resistance to a 10mg bumetanide challenge, defined as: 1. FENa \<10% and total sodium output \<150mmol and 2. At least one of the following criteria: 1\. Chronic home furosemide dose \> or equal to 80mg furosemide equivalents daily 2. eGFR \< 60ml/min 3. Serum chloride \<100mmol/L 4. FENa \<5% and total sodium output \<75mmol on the 2 hour screening Exclusion Criteria: 1. GFR \<20 ml/min/1.73m2 using the CKD-EPI equation or use of renal replacement therapies 2. Use of any non-loop type diuretic in the last 7 days or 5 half lives, with the exclusion of low dose aldosterone antag