Using probenecid to treat heart failure in veterans

Treatment of Veterans With Heart Failure With Reduced Ejection Fraction With Probenecid

This study is testing if probenecid, a drug usually for gout, can help veterans with heart failure feel better and improve their heart function.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: VA Office of Research and Development (fed)
• Locations: 5 sites (Boston, Massachusetts and 4 other locations)
• Trial ID: NCT04551222 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of probenecid, a drug traditionally used for gout, in treating heart failure with reduced ejection fraction (HFrEF) among outpatient veterans. Participants will receive either probenecid or a placebo for 180 days, with the primary focus on measuring improvements in heart function through ultrasound, exercise capacity, and self-reported health status. The study builds on previous findings that suggest probenecid may enhance cardiac contractility without adverse effects. By repurposing this existing medication, the study seeks to provide a new treatment avenue for a condition with limited current options.

Who should consider this trial

Good fit: Ideal candidates include veterans aged 18 and older with documented heart failure and a left ventricular ejection fraction of 40% or less.

Not a fit: Patients with acute coronary syndrome, end-stage renal disease, or certain cardiac conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve heart function and quality of life for patients with heart failure.

How similar studies have performed: Previous studies have shown promise in using probenecid for heart failure, but this specific approach is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Have documented heart failure as a treated inpatient or outpatient diagnosis in the medical record.
* Left ventricular ejection 40% within the past 12 months either by echocardiogram, cardiac MRI, cardiac CT, nuclear imaging or cardiac catheterization.

NYHA class II-III

* On stable GDMT for at least 2 weeks (including at least an EBM dose of betablocker and RAAS inhibition) consistent with the EPHESUS trial criteria \[16\] or having a documented allergy or adverse reaction to betablocker and/or RAAS inhibition.
* Age 18 years or older.

Exclusion Criteria:

* Acute coronary syndrome or cardiac revascularization within the past 3 months.
* End stage renal disease with renal replacement therapy or creatinine clearance less than 30 ml/min \[17\].
* Cardiac resynchronization therapy within the past 3 months.
* Constrictive pericarditis or restrictive cardiomyopathy on cardiac imaging study (echocardiogram cardiac MRI, cardiac CT) within the last 12 months.
* Ablation for cardiac arrhythmias within the past month.
* Peripartum cardiomyopathy diagnosed within past 6 months. If LVEF is still 40% after 6 months of diagnosis, they can be enrolled into the study.
* Uncorrected cyanotic congenital heart disease.
* Severe right sided valvular disease and/or greater than moderate degree of stenotic or regurgitant left valvular disease.
* Terminal illness with expected survival of less than 12 months.
* Women who are pregnant, breast feeding, or plan to become pregnant during the study. All women in childbearing age will undergo baseline and quarterly urine pregnancy tests to ensure absence of pregnancy since the cardiometabolic assessments will be different during pregnancy.
* Oral therapy with probenecid for any indication during the preceding 3 months.
* Hypersensitivity to probenecid based on prior exposure.
* Inability to provide informed consent or study procedures due to dementia, unstable psychiatric disease, or other cause (e.g. inability to do perform exercise testing).
* Acute gout attack within the previous 3 months.
* History of uric acid kidney stones within the last year. Patient will be removed from the study if they develop urate kidney stones.
* History of blood diseases in the past year: Aplastic anemia, Hemolytic anemia, Leukopenia, Neutropenia, Pancytopenia, Thrombocytopenia or leukemia.
* Creatinine clearance (eGFR) \<30 ml/min.

Where this trial is running

Boston, Massachusetts and 4 other locations

• VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA — Boston, Massachusetts, United States (COMPLETED)
• Cincinnati VA Medical Center, Cincinnati, OH — Cincinnati, Ohio, United States (RECRUITING)
• Louis Stokes VA Medical Center, Cleveland, OH — Cleveland, Ohio, United States (RECRUITING)
• Providence VA Medical Center, Providence, RI — Providence, Rhode Island, United States (RECRUITING)
• Hunter Holmes McGuire VA Medical Center, Richmond, VA — Richmond, Virginia, United States (RECRUITING)

Study contacts

• Principal investigator: Jack Rubinstein, MD — Cincinnati VA Medical Center, Cincinnati, OH
• Study coordinator: Jack Rubinstein, MD

Conditions: Heart Failure, heart failure, probenecid