Mechanisms of Diuretic Resistance in Heart Failure, Aim 3
Recruiting
Phase 1Interventional Study
Heart FailureDiuretic Resistance
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At a Glance
Age
18 and older
Sex
Any
Trial phase
Phase 1
Study type
Interventional
Purpose
Other
Participants needed
50 (estimated)
Sponsor
Yale University · Other
Who this trial is looking for
This trial is looking for people with heart failure who have trouble responding to diuretics. Participants will take part in a study to understand how diuresis resistance works and will receive treatments in a crossover manner.
Are You a Good Fit for This Trial?
Rules you outLiver failure
You may be able to join if
I have been diagnosed with heart failure.
I am over 18 years old.
I have not been hospitalized in the last 2 months.
I have stable symptoms and weight.
My potassium level is 5.0 mmol/L or lower.
My sodium level is 130 mEq/L or higher.
My hemoglobin is 8 g/dL or higher.
I have objective evidence of diuretic resistance.
You may not be able to join if
My GFR is lower than 20 ml/min.
I have had any non-loop diuretic in the last 7 days.
I have a history of flash pulmonary edema.
My hemoglobin is lower than 8 g/dL.
I am pregnant or breastfeeding.
I have liver disease or cirrhosis.
I have a history of metabolic or respiratory acidosis in the last 30 days.
I cannot give informed consent or follow the study protocol.
Summarized in plain language from this trial's official eligibility criteria.
The full criteria are further down this page — only the research team can
confirm whether you qualify.
Think this trial could be right for you?
Answer a few quick questions to see if you may meet the eligibility requirements.
Randomized double-blind placebo-controlled crossover study design
Trial Locations
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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 p…
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
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