The Re-Prosper HF Study

• Status: Recruiting
• Trial end date: 2025-11-03
• Target enrollment: 0
• Participant gender: All

Summary

Heart failure with reduced ejection fraction (HFrEF) is a common cause for admission within the Veterans Affairs (VA) Health Care System.

It is associated with severe impairment of physical and mental health status and carries a high risk of mortality. Even though significant progress has been made in understanding the disease process, currently, its management and treatment is limited.

The investigators have discovered that a commonly used drug for the treatment of gout can be repurposed for the treatment of HFrEF.

The objective of this study is the treatment of outpatient Veterans with HFrEF with probenecid to improve heart and health function. Specifically, the investigators are testing whether oral probenecid administered orally twice per day for 180 days improves heart function as measured via ultrasound of the heart (aim 1); improves exercise capacity (aim 2); and improves self-report heart failure specific health status as measured via questionnaires (aim 3).

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: VA Office of Research and Development
• Treatments: Probenecid

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.

• History of admission to the hospital (or equivalent) for the treatment of acute decompensated heart failure (ADHF) within the past 1-12 months.

• Equivalent to hospitalization for ADHF

• Urgent care in the Emergency Department for ADHF

• Observation status for the treatment of ADHF

• Administration of intravenous diuretics in an outpatient setting

• IV inotrope use

• 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.

• Admission to the hospital (or equivalent per above) for the treatment of HF within two weeks.

• Uncorrected cyanotic congenital heart disease.

• Greater than moderate degree of stenotic or regurgitant 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.

• Patients on the following medications: cephalosporins, quinolones, penicillins, methotrexate, zidovudine, ganciclovir, and acyclovir; since the excretion of these drugs is reduced due to probenecid [17]. If a patient is started on any of these medications the physician will be advised that it may increase their serum levels.

• 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.