Mechanisms of Diuretic Resistance in Heart Failure, Aim 2
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests whether adding bendroflumethiazide, amiloride, or both to bumetanide helps water pills work better. It compares these drugs with a placebo, which has no active medicine. It is for adults with heart failure whose bodies do not respond well to water pills.
Randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- You are older than 18 and have a diagnosis of heart failure.
- No changes to your heart failure medicines or device treatments are planned during the study.
- You have had no unplanned hospital stays in the past 2 weeks.
- Your symptoms, exam, and weight show that your body has the right amount of fluid.
- Your blood potassium is 5.0 mmol/L or lower, and your blood sodium is 130 mEq/L or higher.
- Your hemoglobin, a protein in red blood cells, is at least 8 g/dL.
- After a 10 mg bumetanide test dose, your urine shows a poor response: FENa below 10% and total sodium below 150 mmol. FENa measures the share of filtered salt that leaves your body in urine.
- You also meet at least one of these: take a daily water pill dose equal to at least 80 mg of furosemide; have a kidney filtering rate below 60 mL/min; have blood chloride below 100 mmol/L; or have FENa below 5% and urine sodium below 75 mmol at the 2-hour screening.
Who can't join
- Your kidney filtering rate is below 20 mL/min/1.73 m², or you use dialysis or another treatment that replaces kidney function.
- You recently used a water pill outside the loop-diuretic group: within 7 days or 5 drug half-lives, a measure of how long medicine stays in the body. Spironolactone or eplerenone at 50 mg or less is allowed.
- You have had sudden fluid buildup in the lungs that needed hospital care and a breathing machine or pressurized breathing mask. You also cannot join if your heart failure is very sensitive to fluid changes, such as with certain stiff-heart conditions.
- Your hemoglobin is below 8 g/dL, or you have symptoms from anemia, meaning too few healthy red blood cells.
- You are pregnant or breastfeeding, or you have liver failure.
- You cannot give written consent, follow study rules, or attend follow-up visits; or ongoing trouble emptying your bladder prevents timed urine collections.
- You take lithium, pimozide, or thioridazine.
- You are allergic to sulfonamides, thiazide water pills, or bendroflumethiazide, or have another medical reason you cannot take them.
Simplified for readability. The official criteria below are what the study team uses.
Official 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 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, 3. 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). 4. Hemoglobin \< 8 g/dL or symptomatic anemia 5. Pregnant or breastfeeding 6. Inability to give written informed consent or comply with study protocol or follow-up visits 7. Chronic urinary retention limiting ability to perform timed urine collection procedures 8. On Lithium therapy 9. On pimozide or thioridazine 10. Diagnosis of liver failure 11. Contraindications or allergy to sulfonamides 12. Any contraindication to thiazide diuretic or allergy to thiazide or bendroflumethiazide
Study sites (1)
CT
- Yale University · New Haven, CT 06510Veena Rao · Study contactMore trials in New Haven