Mechanisms of Diuretic Resistance in Heart Failure, Aim 2
Recruiting · NCT05753059 · Interventional (participants receive a specific treatment) · Lead sponsor: Yale University
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
Randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide.
Who can take part
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)
Inclusion criteria
- 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 2 weeks
- At optimal volume status by symptoms, exam, and dry weight.
- Serum potassium ≤ 5.0 mmol/L
- Serum sodium ≥ 130 mEq/L
- Age \> 18 years
- Hemoglobin ≥8 g/dL
- Objective evidence of diuretic resistance to a 10mg bumetanide challenge, defined as:
- FENa \<10% and total sodium output \<150mmol and
- At least one of the following criteria:
- \. 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
- GFR \<20 ml/min/1.73m2 using the CKD-EPI equation or use of renal replacement therapies
- Use of any non-loop type diuretic in the last 7 days or 5 half lives, 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, 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 or symptomatic anemia
- 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
- 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
Where it is running
1 location listed across 1 US state.
- Yale University - New Haven, Connecticut, United States