Trial reportJournal of the American Heart Association2018
Probenecid Improves Cardiac Function in Patients With Heart Failure With Reduced Ejection Fraction In Vivo and Cardiomyocyte Calcium Sensitivity In Vitro.
Trial report in Journal of the American Heart Association, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01814319 (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), which is not on this map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Effect of Uric Acid-Lowering Agents on Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.Frontiers in cardiovascular medicine · 2021Pooled it
- Probenecid Improves Cardiac Function in Subjects with a Fontan Circulation and Augments Cardiomyocyte Calcium Homeostasis.Pediatric cardiology · 2020Trial
- Review
- In vivo visualization of cardiac extracellular adenosine dynamics and its pharmacological modulation in zebrafish heart failure models.Scientific reports · 2026Article
- Pannexins in the heart: cell-specific expression and contributions to disease.Cell and tissue research · 2026Review
- Colon-Specific Delivery of Probenecid Enhances Therapeutic Activity of the Uricosuric Agent Against Rat Colitis.Pharmaceutics · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Structural insights into TRPV2 modulation by probenecid.Nature structural & molecular biology · 2025Article
- Probenecid as a pharmacotherapy for alcohol use disorder: A randomized placebo-controlled alcohol interaction trial.Alcohol, clinical & experimental research · 2024Article
- TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases.Signal transduction and targeted therapy · 2023Review
- Probenecid affects muscle Ca2+ homeostasis and contraction independently from pannexin channel block.The Journal of general physiology · 2023Article
- Article
- Cardiovascular risk associated with allopurinol vs. benzbromarone in patients with gout.European heart journal · 2021Article
- Role of Known Transient Receptor Potential Vanilloid Channels in Modulating Cardiac Mechanobiology.Frontiers in physiology · 2021Review
- TRPV2 channel as a possible drug target for the treatment of heart failure.Laboratory investigation; a journal of technical methods and pathology · 2020Review
- The Control of Diastolic Calcium in the Heart: Basic Mechanisms and Functional Implications.Circulation research · 2020Review
- Probenecid treatment improves outcomes in a novel mouse model of peripartum cardiomyopathy.PloS one · 2020Article
- Probenecid: An Oral Inotrope for End-Stage Heart Failure in a Case With Myotonic Dystrophy.JACC. Case reports · 2019Article
- Cardiovascular Safety of Urate Lowering Therapies.Current rheumatology reports · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundTransient receptor potential vanilloid 2 is a calcium channel activated by probenecid. Probenecid is a Food and Drug Administration-approved uricosuric drug that has recently been shown to induce positive lusitropic and inotropic effects in animal models through cardiomyocyte transient receptor potential vanilloid 2 activation. The aim of this study was to test the hypothesis that oral probenecid can improve cardiac function and symptomatology in patients with heart failure with reduced ejection fraction and to further elucidate its calcium-dependent effects on myocyte contractility. METHODS AND
resultsThe clinical trial recruited stable outpatients with heart failure with reduced ejection fraction randomized in a single-center, double-blind, crossover design. Clinical data were collected including a dyspnea assessment, physical examination, ECG, echocardiogram to assess systolic and diastolic function, a 6-minute walk test, and laboratory studies. In vitro force generation studies were performed on cardiomyocytes isolated from murine tissue exposed to probenecid or control treatments. The clinical trial recruited 20 subjects (mean age 57 years, mean baseline fractional shortening of 13.6±1.0%). Probenecid therapy increased fractional shortening by 2.1±1.0% compared with placebo -1.7±1.0% (
conclusionsProbenecid improves cardiac function with minimal effects on symptomatology and no significant adverse effects after 1 week in patients with heart failure with reduced ejection fraction and increases force development and calcium sensitivity at the cardiomyocyte level. CLINICAL
trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01814319.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.