Mechanisms of Diuretic Resistance in Heart Failure, Aim 2

• Status: Not yet recruiting
• Trial end date: 2029-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Yale University
• Treatments: Amiloride; Bendroflumethiazide

Criteria

Inclusion Criteria:

1. Chronic clinical diagnosis of HF with a documented ejection fraction <40%.

2. Use of beta blocker, ACE, ARB or neprilysin inhibitor (sacubitril/valsartan), aldosterone antagonist, and SGLT2 inhibitor at ≥50% guideline directed doses for 30 days with no plan for titration/change during the study period.

3. Chronic stable use of ≥80mg furosemide equivalents per day for ≥ 30 days

4. Peak FENa < 5% following 10mg IV bumetanide challenge at the screening visit

5. Absence of hospitalizations in the previous 3 months.

6. At optimal volume status by symptoms, exam, and dry weight.

7. Serum potassium ≤ 5.0 mmol/L

8. Serum sodium ≥ 130 mEq/L

9. Age > 18 years

Exclusion Criteria:

1. GFR <20 ml/min/1.73m2

2. Use of any non-loop type diuretic in the last 14 days with the exclusion of low dose aldosterone antagonist (e.g., spironolactone ≤50 mg)

3. History of flash pulmonary edema or a "brittle" volume sensitive HF phenotype such as amyloid cardiomyopathy

4. Hemoglobin < 8 g/dL

5. Pregnant or breastfeeding

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