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

Systolic Heart Failure Clinical Trial

— ReProsperHF  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01814319
• Other study ID #: Re-Prosper HF
• Status: Completed
• Phase: Phase 2
• First received: March 14, 2013
• Last updated: August 24, 2015
• Start date: March 2013
• Est. completion date: June 2015

Study information

• Verified date: August 2015
• Source: University of Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Systolic
• Systolic Heart Failure

Intervention

Drug:
• Probenecid 1 gr oral twice daily
Probenecid 1 gram oral twice daily
• Placebo
Matching placebo oral twice daily

Locations

Country	Name	City	State
United States	University of Cincinnati	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
University of Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6 minute walk test	Measure for changes in the distance that the patient can walk over 6 minutes.	1 week	No
Primary	shortness of breath	Measure objectively if there are changes in perceived shortness of breath using a standardized scale	1 week	No
Secondary	Ejection fraction	We will measure via echocardiography the systolic function of the heart	1 week	No
Secondary	beta naturietic peptide	We will measure for changes in the beta natuiretic peptide as a marker of cardiac function and dilatation.	1 week	No
Secondary	serum electrolytes	We will measure several important electrolytes such as Na, K and Ca.	1 week	Yes