Understanding Diuretic Resistance in Heart Failure
Mechanisms of Diuretic Resistance in Heart Failure, Aim 3
This study is testing if adding ammonium chloride to the usual diuretic treatment can help people with heart failure who struggle to get rid of excess fluid.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 50 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Yale University Academic / other |
| Locations | 1 site (New Haven, Connecticut) |
| Trial ID | NCT06209359 on ClinicalTrials.gov |
What this trial studies
This interventional study aims to explore the mechanisms behind diuretic resistance in patients with heart failure. Participants will undergo a randomized, double-blind, placebo-controlled crossover design, starting with a diuretic response assessment using IV bumetanide. Following this, they will receive either ammonium chloride or a placebo alongside their regular diuretic treatment, with careful monitoring of their urine output and biochemical parameters. The study includes a washout period before participants switch to the alternate treatment, allowing for a comprehensive evaluation of the effects of the interventions.
Who should consider this trial
Good fit: Ideal candidates are adults over 18 with a clinical diagnosis of heart failure and objective evidence of diuretic resistance.
Not a fit: Patients with a glomerular filtration rate below 20 ml/min or those using non-loop diuretics may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could lead to improved management strategies for patients with heart failure who experience diuretic resistance.
How similar studies have performed: While the specific approach of this study may be novel, similar studies have shown promise in understanding diuretic resistance in heart failure.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
New Haven, Connecticut
- Yale University — New Haven, Connecticut, United States (Recruiting)
Study contacts
- Principal investigator: Jeffrey Testani, MD — Yale University
- Study coordinator: Veena Rao, PHD
- Email: veena.s.rao@yale.edu
- Phone: 2037373571
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.