NCT06209359 · Yale University
Mechanisms of Diuretic Resistance in Heart Failure, Aim 3
(MsDR Aim 3)
What this study is about
randomly assigned where neither patients nor doctors know which treatment is given compared against an inactive treatment crossover study design
View original scientific description
Randomized double-blind placebo-controlled crossover study design
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
Where
- New Haven, Connecticut
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 22, 2026 · Source of record for eligibility and locations