The Re-Prosper HF Study

NCT04551222 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: CARA-006-19FI01CX001968
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 5

Brief 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).

Conditions

Heart Failure

Keywords

heart failure; probenecid

Outcome Measures

Primary Outcomes (1)

• Change from baseline in cardiac function

  The main primary outcome is echocardiogram-derived EF. The investigators will use Definity echo contrast if adequate endocardial border definition cannot be ascertained for EF calculation in apical 4 and apical 2 using volumetric tracing analysis and modified Simpson's. The echosonographers from all sites will follow the same standard study ECHO procedure to obtain the views

  6 months

Secondary Outcomes (2)

• Change from baseline in exercise tolerance via a symptom-limited exercise test on a cycle ergometer

  6 months

• Change from baseline in The Kansas City Cardiomyopathy Questionnaire (KCCQ) and EQ5D

  6 months

Study Arms (2)

Probenecid

ACTIVE COMPARATOR

1 gr. orally of probenecid twice daily for 180 days

Drug: probenecid

Placebo

PLACEBO COMPARATOR

identical placebo (to probenecid tablets) for 180 days

Drug: Placebo

Interventions

probenecid DRUG

1 gr. orally of probenecid twice daily for 180 days

Probenecid

Placebo DRUG

identical tablets to probenecid

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (5)

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, 02130-4817, United States

Location

Cincinnati VA Medical Center, Cincinnati, OH

Cincinnati, Ohio, 45220-2213, United States

Location

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, 44106-1702, United States

Location

Providence VA Medical Center, Providence, RI

Providence, Rhode Island, 02908-4734, United States

Location

Hunter Holmes McGuire VA Medical Center, Richmond, VA

Richmond, Virginia, 23249-0001, United States

Location

Related Publications (1)

• Rubinstein J, Robbins N, Evans K, Foster G, Mcconeghy K, Onadeko T, Bunke J, Parent M, Luo X, Joseph J, Wu WC. Repurposing Probenecid for the Treatment of Heart Failure (Re-Prosper-HF): a study protocol for a randomized placebo-controlled clinical trial. Trials. 2022 Apr 7;23(1):266. doi: 10.1186/s13063-022-06214-y.

  PMID: 35392963 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

Probenecid

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Study Officials

• Jack Rubinstein, MD

  Cincinnati VA Medical Center, Cincinnati, OH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: This is a three-site, double-blinded, randomized, placebo controlled, parallel design, trial in a 1:1 fashion of 1 gr. orally of probenecid twice daily or identical placebo for 180 days. The investigators propose to recruit 120 subjects (power analysis below) with HFrEF (LVEF 40%), NYHA II-III on guideline directed medical therapy.

Study Record Dates

• First Submitted: September 9, 2020
• First Posted: September 16, 2020
• Study Start: June 9, 2021
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)