Systolic Heart FailurePhase 2ReProsperHFNCT01814319
Repurposing Probenecid as a Positive Inotrope for the Treatment of Heart Failure
A Phase 2 study testing Probenecid 1 gr oral twice daily in people with Systolic Heart Failure, run by University of Cincinnati at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Systolic Heart Failure
- What is being tested?
- Probenecid 1 gr oral twice daily
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to Jun 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age or older
- EF < 40% via echocardiogram within the past 12 months
- Stable dose of heart failure medications for > past 1 month
- NYHA class II - IV
Who cannot join
- Pregnant or lactating female
- Receiving IV inotrope
- History of significant non-compliance
- Unwilling to adhere to the protocol
- Systemic systolic BP less than 90 mmHg at screening visit
- History of allergy to probenecid
Show all 16Show fewer
- History of gout
- History of renal calculi
- Recent unstable coronary artery syndromes (USA, admission to hospital for AMI, revascularization procedure, or acute decompensated HF requiring hospitalization) within the past 3 months.
- Implant of CRT device within the past 3 months
- TIA, CVA or major surgery within the past 3 months
- Valvular heart disease (more than moderate stenosis or insufficiency)
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Systolic Heart Failure
- Being tested
- Probenecid 1 gr oral twice daily, Placebo
- Keywords
- heart failure, ejection fraction equal or less than 40%
- Medical subject headings
- Heart Failure, Systolic, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probenecid 1 gr oral twice dailyDrug
Probenecid 1 gram oral twice daily
PlaceboDrug
Matching placebo oral twice daily
| Study group | Role | What they receive |
|---|---|---|
| Probenecid | Experimental | 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. Receives: Drug: Probenecid 1 gr oral twice daily |
| placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
6 minute walk test
Measure for changes in the distance that the patient can walk over 6 minutes.
Measured: 1 week
shortness of breath
Measure objectively if there are changes in perceived shortness of breath using a standardized scale
Measured: 1 week
Secondary outcomes (3)
Ejection fraction
We will measure via echocardiography the systolic function of the heart
Measured: 1 week
beta naturietic peptide
We will measure for changes in the beta natuiretic peptide as a marker of cardiac function and dilatation.
Measured: 1 week
serum electrolytes
We will measure several important electrolytes such as Na, K and Ca.
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2013 (estimated)
- Study startMar 2013
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Systolic Heart FailureStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jack Rubinstein, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01814319
- Sponsor's protocol ID
- Re-Prosper HF
- Acronym
- ReProsperHF
- Status last verified
- Aug 2015
- First submitted
- 14 Mar 2013
- Last updated
- 26 Aug 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Robbins N, Gilbert M, Kumar M, McNamara JW, Daly P, Koch SE, Conway G, Effat M, Woo JG, Sadayappan S, Rubinstein J. Probenecid Improves Cardiac Function in Patients With Heart Failure With Reduced Ejection Fraction In Vivo and Cardiomyocyte Calcium Sensitivity In Vitro. J Am Heart Assoc. 2018 Jan 13;7(2):e007148. doi: 10.1161/JAHA.117.007148.
PubMed 29331959
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01814319
- Acronym / sponsor ID
- ReProsperHF / Re-Prosper HF
- Conditions
- Systolic Heart Failure
- Keywords
- heart failure, ejection fraction equal or less than 40%
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 19 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probenecid | Experimental | Drug: Probenecid 1 gr oral twice dailyProbenecid 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. |
| placebo | Placebo comparator | Drug: PlaceboProbenecid 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 18 years of age or older
- EF < 40% via echocardiogram within the past 12 months
- Stable dose of heart failure medications for > past 1 month
- NYHA class II - IV
Key exclusion criteria (16 listed)
- Pregnant or lactating female
- Receiving IV inotrope
- History of significant non-compliance
- Unwilling to adhere to the protocol
- Systemic systolic BP less than 90 mmHg at screening visit
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probenecid 1 gr oral twice dailyProbenecid 1 gram oral twice daily | Drug | Probenecid |
| PlaceboMatching placebo oral twice daily | Drug | placebo |
Primary outcome
6 minute walk test
Time frame: 1 week
Measure for changes in the distance that the patient can walk over 6 minutes.
shortness of breath
Time frame: 1 week
Measure objectively if there are changes in perceived shortness of breath using a standardized scale
3 secondary outcomes
Ejection fraction
Time frame: 1 week
beta naturietic peptide
Time frame: 1 week
serum electrolytes
Time frame: 1 week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2015.
- Derived from this study: PubMed 29331959Robbins N, Gilbert M, Kumar M, McNamara JW, Daly P, Koch SE, Conway G, Effat M, Woo JG, Sadayappan S, Rubinstein J. Probenecid Improves Cardiac Function in Patients With Heart Failure With Reduced Ejection Fraction In Vivo and Cardiomyocyte Calcium Sensitivity In Vitro. J Am Heart Assoc. 2018 Jan 13;7(2):e007148. doi: 10.1161/JAHA.117.007148.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Probenecid 1 gr oral twice daily in people with Systolic Heart Failure, run by University of Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6 minute walk test (time frame: 1 week). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01814319, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2015.