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Repurposing Probenecid as a Positive Inotrope for the Treatment of Heart Failure (ReProsperHF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01814319
Recruitment Status : Completed
First Posted : March 19, 2013
Last Update Posted : August 26, 2015
Sponsor:
Information provided by (Responsible Party):
Jack Rubinstein, University of Cincinnati

Brief 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.

Condition or disease Intervention/treatment Phase
Systolic Heart Failure Drug: Probenecid 1 gr oral twice daily Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Initial Study on the Use of Probenecid as a Positive Inotrope for the Treatment of Systolic Heart Failure in Stable NYHA Class II to IV Patients
Study Start Date : March 2013
Actual Primary Completion Date : June 2015
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure
Drug Information available for: Probenecid

Arm Intervention/treatment
Experimental: Probenecid
Probenecid 1 gr oral twice daily or placebo will be given to the subject for 1 week (randomly assigned). A subsequent 1 week washout period will occur followed by the alternate therapy.
Drug: Probenecid 1 gr oral twice daily
Probenecid 1 gram oral twice daily

Placebo Comparator: placebo
Probenecid 1 gr oral twice daily or placebo will be given to the subject for 1 week (randomly assigned). A subsequent 1 week washout period will occur followed by the alternate (placebo) therapy.
Drug: Placebo
Matching placebo oral twice daily




Primary Outcome Measures :
  1. 6 minute walk test [ Time Frame: 1 week ]
    Measure for changes in the distance that the patient can walk over 6 minutes.

  2. shortness of breath [ Time Frame: 1 week ]
    Measure objectively if there are changes in perceived shortness of breath using a standardized scale


Secondary Outcome Measures :
  1. Ejection fraction [ Time Frame: 1 week ]
    We will measure via echocardiography the systolic function of the heart

  2. beta naturietic peptide [ Time Frame: 1 week ]
    We will measure for changes in the beta natuiretic peptide as a marker of cardiac function and dilatation.

  3. serum electrolytes [ Time Frame: 1 week ]
    We will measure several important electrolytes such as Na, K and Ca.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. 18 years of age or older
  2. EF < 40% via echocardiogram within the past 12 months
  3. Stable dose of heart failure medications for > past 1 month
  4. NYHA class II - IV

Exclusion Criteria

  1. Pregnant or lactating female
  2. Receiving IV inotrope
  3. History of significant non-compliance
  4. Unwilling to adhere to the protocol
  5. Systemic systolic BP less than 90 mmHg at screening visit
  6. History of allergy to probenecid
  7. History of gout
  8. History of renal calculi
  9. Recent unstable coronary artery syndromes (USA, admission to hospital for AMI, revascularization procedure, or acute decompensated HF requiring hospitalization) within the past 3 months.
  10. Implant of CRT device within the past 3 months
  11. TIA, CVA or major surgery within the past 3 months
  12. Valvular heart disease (more than moderate stenosis or insufficiency)
  13. HOCM, myocarditis, constrictive pericarditis, congenital heart disease, 14 Active chemotherapy, significant malignancy or uncontrolled metabolic disease (untreated hyper or hypothyroidism, Cushing's disease etc.)What about uncontrolled DM?? HgA1C > etc

15. Elevated liver enzymes (> 3 times ULN), 16. Current atrial fibrillation or frequent PVCs (should we define this now) 17. End stage renal disease (dialysis dependent) or worsening renal insufficiency should define now.

18. History of gastric ulcerations, significant gastroesophageal reflux. 19. Other condition that in the opinion of the investigator, would make the subject a poor candidate for the study.

20. Co-administration of any medication that in the opinion of the investigator places the subject at increased risks due to potential adverse drug interactions.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01814319


Locations
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United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
Sponsors and Collaborators
University of Cincinnati
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Jack Rubinstein, Asst Professor, University of Cincinnati
ClinicalTrials.gov Identifier: NCT01814319    
Other Study ID Numbers: Re-Prosper HF
First Posted: March 19, 2013    Key Record Dates
Last Update Posted: August 26, 2015
Last Verified: August 2015
Keywords provided by Jack Rubinstein, University of Cincinnati:
heart failure
ejection fraction equal or less than 40%
Additional relevant MeSH terms:
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Heart Failure
Heart Failure, Systolic
Systolic Murmurs
Heart Diseases
Cardiovascular Diseases
Heart Murmurs
Probenecid
Uricosuric Agents
Gout Suppressants
Antirheumatic Agents
Renal Agents