Ignite Creation Date:
2024-05-06 @ 3:12 PM
Last Modification Date:
2024-10-26 @ 1:44 PM
Study NCT ID:
NCT04551222
Status:
RECRUITING
Last Update Posted:
2024-05-22
First Post:
2020-09-09
Brief Title:
The Re-Prosper HF Study
Sponsor:
VA Office of Research and Development
Organization:
VA Office of Research and Development
Study Overview
Official Title:
Treatment of Veterans With Heart Failure With Reduced Ejection Fraction With Probenecid
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Re-Prosper HF
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
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
Detailed Description:
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 5-yr mortality rate of 75 Even though significant progress has been made in understanding its pathophysiology currently its management and treatment is based on therapeutic targeting of a limited number of receptors and pathways
The investigators team and others have made great progress in the last few years by understanding and harnessing the Transient Potential Receptor superfamily as regulators of cardiovascular function Specifically the investigators laboratory has explored the role the vanilloid 2 TRPV2 subtype plays in regulating calcium handling and contractility This work has led researchers to understand that TRPV2 modulates contractility via increasing calcium cycling in myocytes on a beat-to-beat basis
The investigators have used probenecid a generic globally available drug with an extremely safe profile that has been used for decades as a treatment for gout as a TRPV2 agonist The investigators work with this drug has demonstrated it to be a potent inotrope without apoptotic chronotropic or arrhythmogenic effects in cardiomyocytes in vitro as well as in vivo murine and porcine models These findings have been taken to the bedside with a recently published small phase 2 study of 20 adult patients with HFrEF the ReProsper HF pilot study where the investigators demonstrated a mean improvement in left ventricular systolic and diastolic function with no adverse effects after only 1 week of treatment The use of probenecid in HFrEF was also indirectly supported by a recent retrospective study of approximately 40000 patients in the Medicare database that found treatment with probenecid not specifically for heart disease was associated with a 9 decreased risk of HF hospitalization These studies strongly argue for the safety and potential efficacy of probenecid to improve systolic function and the need for a larger study and of longer duration that also evaluates functional and health status outcomes in addition to systolic function
The overall objective of this study is the treatment of outpatient Veterans with NYHA II-III heart failure with reduced ejection fraction HFrEF with probenecid to improve systolic and health function Specifically the investigators are proposing a three-site double-blinded randomized placebo-controlled trial that will assess whether oral probenecid administered at 1 gr orally twice per day for 180 days in patients with NYHA II-III HFrEF improves systolic function as measured via ejection fraction with echocardiography aim 1 improves functional status as measured by exercise stress testing aim 2 and improves self-report heart failure specific health status as measured by Kansas City Cardiomyopathy Questionnaire KCCQ and overall health status measured by EQ5D aim 3
The investigators team and others have made great progress in the last few years by understanding and harnessing the Transient Potential Receptor superfamily as regulators of cardiovascular function Specifically the investigators laboratory has explored the role the vanilloid 2 TRPV2 subtype plays in regulating calcium handling and contractility This work has led researchers to understand that TRPV2 modulates contractility via increasing calcium cycling in myocytes on a beat-to-beat basis
The investigators have used probenecid a generic globally available drug with an extremely safe profile that has been used for decades as a treatment for gout as a TRPV2 agonist The investigators work with this drug has demonstrated it to be a potent inotrope without apoptotic chronotropic or arrhythmogenic effects in cardiomyocytes in vitro as well as in vivo murine and porcine models These findings have been taken to the bedside with a recently published small phase 2 study of 20 adult patients with HFrEF the ReProsper HF pilot study where the investigators demonstrated a mean improvement in left ventricular systolic and diastolic function with no adverse effects after only 1 week of treatment The use of probenecid in HFrEF was also indirectly supported by a recent retrospective study of approximately 40000 patients in the Medicare database that found treatment with probenecid not specifically for heart disease was associated with a 9 decreased risk of HF hospitalization These studies strongly argue for the safety and potential efficacy of probenecid to improve systolic function and the need for a larger study and of longer duration that also evaluates functional and health status outcomes in addition to systolic function
The overall objective of this study is the treatment of outpatient Veterans with NYHA II-III heart failure with reduced ejection fraction HFrEF with probenecid to improve systolic and health function Specifically the investigators are proposing a three-site double-blinded randomized placebo-controlled trial that will assess whether oral probenecid administered at 1 gr orally twice per day for 180 days in patients with NYHA II-III HFrEF improves systolic function as measured via ejection fraction with echocardiography aim 1 improves functional status as measured by exercise stress testing aim 2 and improves self-report heart failure specific health status as measured by Kansas City Cardiomyopathy Questionnaire KCCQ and overall health status measured by EQ5D aim 3
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| I01CX001968 | NIH | None | httpsreporternihgovquickSearchI01CX001968 |