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0 0.5 1 1.5 2+ WHO scale, 1000mg 90% Improvement Relative Risk WHO scale, 500mg 80% Recovery, 1000mg 60% Recovery, 500mg 45% Time to viral-, 1000mg 36% Time to viral-, 500mg 18% Probenicid  Martin et al.  EARLY TREATMENT  RCT Is early treatment with probenicid beneficial for COVID-19? RCT 75 patients in India (July - September 2022) Improved recovery (p<0.0001) and faster viral clearance (p=0.0001) c19early.org Martin et al., Viruses, July 2023 Favors probenicid Favors control

Oral Probenecid for Nonhospitalized Adults with Symptomatic Mild-to-Moderate COVID-19

Martin et al., Viruses, doi:10.3390/v15071508, NCT05442983
Jul 2023  
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RCT 75 outpatients in India with mild to moderate COVID-19 showing faster viral clearance, faster time to symptom resolution, and improvement in disease progression with probenecid treatment for 5 days compared to placebo. Probenecid was well tolerated with only mild adverse events noted. There was a dose-dependent response, with probenecid 1000mg twice daily performing better than 500mg twice daily.
relative WHO scale, 90.0% better, RR 0.10, p < 0.001, treatment mean 0.1 (±0.4) n=25, control mean 1.0 (±0.89) n=25, day 10, 1000mg.
relative WHO scale, 80.0% better, RR 0.20, p < 0.001, treatment mean 0.2 (±0.55) n=25, control mean 1.0 (±0.89) n=25, day 10, 500mg.
risk of no recovery, 60.0% lower, RR 0.40, p = 0.001, treatment 8 of 25 (32.0%), control 20 of 25 (80.0%), NNT 2.1, day 10, 1000mg.
risk of no recovery, 45.0% lower, RR 0.55, p = 0.02, treatment 11 of 25 (44.0%), control 20 of 25 (80.0%), NNT 2.8, day 10, 500mg.
time to viral-, 36.4% lower, relative time 0.64, p < 0.001, treatment 25, control 25, 1000mg.
time to viral-, 18.2% lower, relative time 0.82, p < 0.001, treatment 25, control 25, 500mg.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Martin et al., 6 Jul 2023, Single Blind Randomized Controlled Trial, placebo-controlled, India, peer-reviewed, 7 authors, study period 18 July, 2022 - 9 September, 2022, trial NCT05442983 (history). Contact: davidmartin@trippbio.com (corresponding author), ratripp@uga.edu.
This PaperMiscellaneousAll
Oral Probenecid for Nonhospitalized Adults with Symptomatic Mild-to-Moderate COVID-19
David E Martin, Neelam Pandey, Purvi Chavda, Gurpreet Singh, Rakesh Sutariya, Frederic Sancilio, Ralph A Tripp
Viruses, doi:10.3390/v15071508
Probenecid is an orally bioavailable, uricosuric agent that was first approved in 1951 for the treatment of gout, but was later found to have potent, broad-spectrum antiviral activity against several respiratory viruses including SARS-CoV-2. We conducted a phase 2 randomized, placebocontrolled, single-blind, dose-range finding study in non-hospitalized patients with symptomatic, mild-to-moderate COVID-19. Patients were randomly assigned in a 1:1:1 ratio to receive either 500 mg of probenecid, 1000 mg of probenecid, or a matching placebo every 12 h for five days. The patients' COVID-19 viral load hospitalization, or death from any cause through day 28, as well as safety, were evaluated. COVID-19-related symptoms were assessed at baseline, and on days 3, 5, 10, 15, and 28. The primary endpoints of the study were time to first negative SARS-CoV-2 viral test (or viral clearance) and the proportion of patients that were symptom-free at day 5. A total of 75 patients were randomized, with 25 patients in each group. All of the patients completed the study as planned with no hospitalizations or deaths being reported. The median time to viral clearance was significantly shorter for the probenecid 1000 mg group than for placebo (7 days vs. 11 days, respectively; p < 0.0001), and for the probenecid 500 mg group versus placebo (9 days vs. 11 days, respectively; p < 0.0001). In addition, the median time to viral clearance was significantly shorter for the probenecid 1000 mg group than for the probenecid 500 mg group (7 days vs. 9 days, respectively; p < 0.0001). All patients reported at least one COVID-19-related symptom on days 3 and 5; however, on day 10, a significantly greater proportion of patients receiving probenecid 1000 mg reported the complete resolution of symptoms versus placebo (68% vs. 20%, respectively; p = 0.0006), as well as for those receiving probenecid 500 mg versus placebo (56% vs. 20%, respectively, p = 0.0087). The incidence of adverse events during treatment was similar across all groups for any adverse event, and was 12%. All events were mild with no serious adverse events reported and no discontinuations due to an adverse event. The treatment of patients with symptomatic, mild-to-moderate COVID-19 with probenecid resulted in a significant, dose-dependent decrease in the time to viral clearance and a significantly higher proportion of patients reporting complete symptom resolution by day 10. (Supported by TrippBio; ClinicalTrials.gov number, NCT05442983 and Clinical Trials Registry India number CTRI/2022/07/043726).
Conflicts of Interest: D.E.M is an employee and shareholder of TrippBio, Inc. F.S. and R.A.T. are shareholders of TrippBio, Inc. R.A.T. is an inventor on a granted patent application owned by the University of Georgia Research Foundation covering the method of use of probenecid as a treatment for coronavirus infections.
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Zeke, Misheva, Reményi, Bogoyevitch, JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships, Microbiol. Mol. Biol. Rev, doi:10.1128/MMBR.00043-14
{ 'DOI': '10.3390/v15071508', 'ISSN': ['1999-4915'], 'URL': 'http://dx.doi.org/10.3390/v15071508', 'abstract': '<jats:p>Probenecid is an orally bioavailable, uricosuric agent that was first approved in ' '1951 for the treatment of gout, but was later found to have potent, broad-spectrum antiviral ' 'activity against several respiratory viruses including SARS-CoV-2. We conducted a phase 2 ' 'randomized, placebo-controlled, single-blind, dose-range finding study in non-hospitalized ' 'patients with symptomatic, mild-to-moderate COVID-19. Patients were randomly assigned in a ' '1:1:1 ratio to receive either 500 mg of probenecid, 1000 mg of probenecid, or a matching ' 'placebo every 12 h for five days. The patients’ COVID-19 viral load hospitalization, or death ' 'from any cause through day 28, as well as safety, were evaluated. COVID-19-related symptoms ' 'were assessed at baseline, and on days 3, 5, 10, 15, and 28. The primary endpoints of the ' 'study were time to first negative SARS-CoV-2 viral test (or viral clearance) and the ' 'proportion of patients that were symptom-free at day 5. A total of 75 patients were ' 'randomized, with 25 patients in each group. All of the patients completed the study as ' 'planned with no hospitalizations or deaths being reported. The median time to viral clearance ' 'was significantly shorter for the probenecid 1000 mg group than for placebo (7 days vs. 11 ' 'days, respectively; p &lt; 0.0001), and for the probenecid 500 mg group versus placebo (9 ' 'days vs. 11 days, respectively; p &lt; 0.0001). In addition, the median time to viral ' 'clearance was significantly shorter for the probenecid 1000 mg group than for the probenecid ' '500 mg group (7 days vs. 9 days, respectively; p &lt; 0.0001). All patients reported at least ' 'one COVID-19-related symptom on days 3 and 5; however, on day 10, a significantly greater ' 'proportion of patients receiving probenecid 1000 mg reported the complete resolution of ' 'symptoms versus placebo (68% vs. 20%, respectively; p = 0.0006), as well as for those ' 'receiving probenecid 500 mg versus placebo (56% vs. 20%, respectively, p = 0.0087). The ' 'incidence of adverse events during treatment was similar across all groups for any adverse ' 'event, and was 12%. All events were mild with no serious adverse events reported and no ' 'discontinuations due to an adverse event. The treatment of patients with symptomatic, ' 'mild-to-moderate COVID-19 with probenecid resulted in a significant, dose-dependent decrease ' 'in the time to viral clearance and a significantly higher proportion of patients reporting ' 'complete symptom resolution by day 10. (Supported by TrippBio; ClinicalTrials.gov number, ' 'NCT05442983 and Clinical Trials Registry India number CTRI/2022/07/043726).</jats:p>', 'alternative-id': ['v15071508'], 'author': [ { 'ORCID': 'http://orcid.org/0000-0003-2820-5983', 'affiliation': [{'name': 'TrippBio, Inc., Jacksonville, FL 32256, USA'}], 'authenticated-orcid': False, 'family': 'Martin', 'given': 'David E.', 'sequence': 'first'}, { 'affiliation': [ { 'name': 'PCMC’s PGI Yashwantrao Chavan Memorial Hospital, Pune 411018, ' 'India'}], 'family': 'Pandey', 'given': 'Neelam', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Zenovel Pharma Services LLP, Ahmedabad 380060, India'}], 'family': 'Chavda', 'given': 'Purvi', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Clearway Global, Stuart, FL 34997, USA'}], 'family': 'Singh', 'given': 'Gurpreet', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Zenovel Pharma Services LLP, Ahmedabad 380060, India'}], 'family': 'Sutariya', 'given': 'Rakesh', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Clearway Global, Stuart, FL 34997, USA'}], 'family': 'Sancilio', 'given': 'Frederic', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0002-2924-9956', 'affiliation': [ { 'name': 'Department of Infectious Diseases, College of Veterinary ' 'Medicine, University of Georgia, Athens, GA 30602, USA'}], 'authenticated-orcid': False, 'family': 'Tripp', 'given': 'Ralph A.', 'sequence': 'additional'}], 'container-title': 'Viruses', 'container-title-short': 'Viruses', 'content-domain': {'crossmark-restriction': False, 'domain': []}, 'created': {'date-parts': [[2023, 7, 7]], 'date-time': '2023-07-07T05:41:36Z', 'timestamp': 1688708496000}, 'deposited': { 'date-parts': [[2023, 7, 7]], 'date-time': '2023-07-07T06:46:52Z', 'timestamp': 1688712412000}, 'funder': [{'name': 'TrippBio, Inc.'}], 'indexed': {'date-parts': [[2024, 1, 23]], 'date-time': '2024-01-23T10:00:37Z', 'timestamp': 1706004037294}, 'is-referenced-by-count': 3, 'issue': '7', 'issued': {'date-parts': [[2023, 7, 6]]}, 'journal-issue': {'issue': '7', 'published-online': {'date-parts': [[2023, 7]]}}, 'language': 'en', 'license': [ { 'URL': 'https://creativecommons.org/licenses/by/4.0/', 'content-version': 'vor', 'delay-in-days': 0, 'start': { 'date-parts': [[2023, 7, 6]], 'date-time': '2023-07-06T00:00:00Z', 'timestamp': 1688601600000}}], 'link': [ { 'URL': 'https://www.mdpi.com/1999-4915/15/7/1508/pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'member': '1968', 'original-title': [], 'page': '1508', 'prefix': '10.3390', 'published': {'date-parts': [[2023, 7, 6]]}, 'published-online': {'date-parts': [[2023, 7, 6]]}, 'publisher': 'MDPI AG', 'reference': [ { 'DOI': '10.1097/JCMA.0000000000000270', 'article-title': 'The outbreak of COVID-19: An overview', 'author': 'Wu', 'doi-asserted-by': 'crossref', 'first-page': '217', 'journal-title': 'J. 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