Oral Probenecid for Nonhospitalized Adults with Symptomatic Mild-to-Moderate COVID-19
et al., Viruses, doi:10.3390/v15071508, NCT05442983, Jul 2023
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.
Oral Probenecid for Nonhospitalized Adults with Symptomatic Mild-to-Moderate COVID-19
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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