Repurposing Probenecid as a Positive Inotrope for the Treatment of Heart Failure
Condition: Systolic Heart Failure
MeSH terms: Heart Failure; Heart Failure, Systolic; Systolic Murmurs
Study type: Interventional
Phase: Phase 2

Summary: 
      Probenecid is an FDA approved drug for the treatment gout and hyperuricemia. It has been used
      safely in humans for decades for this and other indications. The investigators have recently
      discovered that this drug can also stimulate other receptors in the heart and therefore
      improve its function. The hypothesis of this study is that probenecid can be used to improve
      the function of the heart and therefore the symptoms in patients with heart failure.
    

Detailed description: 
      The investigators will test the hypothesis that oral administration of probenecid results in
      improved symptomatology and heart function in patients with systolic heart failure. There
      will be three cohorts.

      Cohort 1 will enroll up to 50 subjects in a double-blinded, randomized, placebo-control,
      cross-over study with each patient serving as his or her own control. The subjects will have
      stable HF, an ejection fraction of less than or equal to 40% and NYHA II to IV symptoms. Each
      subject will undergo 1 week of investigational product (IP), consisting of oral probenecid
      therapy 1 gram twice a day or placebo with weekly follow.

      The subjects will undergo EKGs, laboratory analysis, physical exams; dyspnea and quality of
      life questionnaires and a 6 minute walk test (MWT) at baseline. There will be 2 optional
      sub-studies one for echocardiographic data and the other biomarkers.

      Cohort 2 will enroll up to 50 subjects in a double-blinded, randomized, placebo-control study
      and will include patients admitted to the hospital with acute decompensated HF. Each subject
      will also receive Investigational product consisting of either 1 gram orally twice daily of
      probenecid or placebo during their hospitalization. They will have daily follow-up with EKG
      and appropriate laboratory work. In addition to the EKG, laboratory analysis, physical exams,
      dyspnea and quality of life questionnaires and 6 MWT data will be collected; additional data
      such as length of hospital stay, biomarkers, use of inotropic therapy and diuretics, and rate
      of diuresis will also be collected.

      Cohort 3 will enroll up to 50 healthy subjects in a double-blinded, randomized,
      placebo-control study. Each subject will also receive Investigational product consisting of
      either 2 grams orally of probenecid or placebo. During a 6 hour course subjects will have
      laboratory analysis, physical exam, telemetry, EKG and echocardiographic studies performed as
      measures of both safety and effect of the compound.
    

Intervention name(s): Probenecid 1 gr oral twice daily; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Probenecid 1 gram oral twice daily; Matching placebo oral twice daily
Intervention MeSH terms: Probenecid
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: heart failure; ejection fraction equal or less than 40%