Back to search results

Understanding Diuretic Resistance in Heart Failure

This study is looking at why some people with heart failure don't respond well to 'water pills' (diuretics), a condition called diuretic resistance. You would receive either ammonium chloride or a placebo (an inactive substance) along with standard diuretics like bumetanide, bendroflumethiazide, and amiloride. After a break, you would then switch to the other treatment. Researchers will measure changes in how your body handles sodium to understand how these treatments affect diuretic resistance. To join, you need a heart failure diagnosis, stable heart failure medications, no recent hospitalizations, and a specific potassium level (serum potassium ≤ 5). This study aims to find out if ammonium chloride can help improve how diuretics work.

Study design
This is a randomized, double-blind, placebo-controlled crossover study, meaning you have an equal chance of receiving either ammonium chloride or placebo, and neither you nor your doctors will know which you are receiving. About 50 participants are expected to join.
What's involved
You would have several visits, including a screening visit to check your diuretic response. You'll follow a special diet for five days before starting the study medication, which you'll take twice daily. You'll also receive IV bumetanide, have blood and urine collected, and potentially receive other IV solutions. After a break of 10 to 28 days, you'll repeat the process with the alternate study medication.
Compensation
Not stated in the trial record.
Follow-up
The primary measurements for this study are taken at Day 0 versus Day 1, and Day 2 versus Day 18, to compare the effects of the treatments.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT06209359

Mechanisms of Diuretic Resistance in Heart Failure, Aim 3

Recruiting
PHASE1Ages 18+Interventional
Yale University
~50 participants
Updated 2026-05-22 on ClinicalTrials.gov
What's tested:Ammonium ChloridePlacebo

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Change of distal sodium reabsorption(ADRNa) between NH4Cl vs. placebo study visits
Measured over Day 0 vs Day 1
+1 more outcome measured

Conditions

Heart Failure
Diuretic Resistance

Explore related trials

CardiomyopathyHeart Failure

Where it's being run

1 sites across 1 states
Connecticut1

Study leadership

  • Jeffrey Testani, MD · PRINCIPAL_INVESTIGATOR · Yale University

Who to contact

Veena Rao, PHD
[email protected]
2037373571
Email the study team

Opens a ready-to-send draft in your own email app — review before sending.

Do you actually qualify for this trial?

Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.

Check eligibility for this trial ~2 min · HIPAA-protected · delete anytime
Eligibility criteria

Inclusion

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

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

What this trial measures

  • Change of distal sodium reabsorption(ADRNa) between NH4Cl vs. placebo study visitsDay 0 vs Day 1

    Comparison of ADRNa between NH4Cl vs. placebo during study visits using fractional excretion of lithium and fractional excretion of sodium to calculate the ADRNa.

  • Change of distal sodium reabsorption(ADRNa) between NH4Cl vs. placebo study visitsDay 2 vs Day 18

    Comparison of ADRNa between NH4Cl vs. placebo during study visits using fractional excretion of lithium and fractional excretion of sodium to calculate the ADRNa.