Mechanisms of Diuretic Resistance in Heart Failure, Aim 3
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 looks at why water pills do not work well in some people with heart failure. It is for adults whose heart failure treatment and fluid levels are stable. Participants receive study treatment and a placebo, which has no active medicine, during different study periods.
Randomized double-blind placebo-controlled crossover study design
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Be older than 18 and have heart failure.
- Have no planned changes to heart failure medicines or heart devices during the study.
- Have had no unplanned hospital stays in the past 2 months.
- Have the right fluid balance, based on symptoms, an exam, and weight without extra fluid.
- Have blood potassium of 5.0 mmol/L or less and sodium of 130 mEq/L or more.
- Have hemoglobin, the protein that carries oxygen in blood, of at least 8 g/dL.
- Show a poor response to a 10 mg dose of bumetanide, a water pill: FENa below 10% and total sodium passed in urine below 150 mmol. FENa measures how much filtered salt leaves the body in urine.
- Also meet at least one condition: regularly take a home 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 on the 2-hour test.
Who can't join
- Have a kidney filtering rate below 20 mL/min/1.73 m² or hemoglobin below 8 g/dL.
- Have used a water pill other than a loop diuretic in the past 7 days. A low-dose aldosterone blocker, such as spironolactone at 50 mg or less, is allowed.
- Have had sudden fluid buildup in the lungs, or have heart failure that is very sensitive to fluid changes, such as heart muscle disease caused by amyloid protein buildup.
- Are pregnant or breastfeeding, or have known liver disease, including liver scarring or liver failure.
- Have had too much acid in the blood in the past 30 days; have blood bicarbonate below 24 mmol/L; or have venous blood pH below 7.35 at screening. These blood tests check acid balance.
- Take acetazolamide or another medicine that can raise blood acid levels. Metformin users may join only if they can safely stop it during each treatment period. Repeated blood sugar readings above 200 mg/dL while in the hospital also prevent joining.
- Take lithium, pimozide, or thioridazine; or have an allergy or another medical reason not to use sulfonamides, thiazide water pills, or bendroflumethiazide.
- Cannot give written consent or follow study instructions and attend follow-up visits.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
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% and total sodium output \<150mmol * And at least one of the following criteria: * Chronic home furosemide dose greater than or equal to 80mg furosemide equivalents * eGFR \< 60ml/min * Serum chloride \<100mmol/L * FENa \<5% and total sodium output \<75mmol on the 2 hour Exclusion Criteria: * Glomerular filtration rate (GFR) \<20 ml/min/1.73m2 * Use of any non-loop type diuretic in the last 7 days with the exclusion of low dose aldosterone antagonist (e.g., spironolactone ≤50 mg) * History of flash pulmonary edema or a "brittle" volume sensitive HF phenotype such as amyloid cardiomyopathy * Hemoglobin \< 8 g/dL * Pregnant or breastfeeding * Cirrhosis or known liver disease * History of metabolic or respiratory acidosis within 30 days * Use of metformin, acetazolamide, or any other agent that could predispose to acidosis * Patients who are on metformin may be enrolled if their metformin can be safely discontinued for the randomized treatment periods in each arm. Any participants who have consistently elevated blood glucose readings \> 200 mg/dL while inpatient will not be enrolled. * Serum bicarbonate level \<24mmol/L at screening visit * Venous potential of hydrogen(pH) \<7.35 at screening visit * Inability to give written informed consent or comply with study protocol or follow-up visits * 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
Study sites (1)
CT
- Yale University · New Haven, CT 06510More trials in New Haven