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0 0.5 1 1.5 2+ Mortality, SR=4 86% Improvement Relative Risk Progression, SR=4 75% Time to improvement, SR=4 9% primary Discharge, SR=4, day 29 89% Discharge, SR=4, day 22 94% Discharge, SR=4, day 15 61% Discharge, SR=4, day 8 11% Viral clearance, SR=4, day.. 67% Viral clearance, SR=4.. (b) 80% Viral clearance, SR=4, day 15 37% Viral clearance, SR=4, day 8 13% Enisamium  Holubovska et al.  LATE TREATMENT  DB RCT Is late treatment with enisamium beneficial for COVID-19? Double-blind RCT 285 patients in Ukraine (May 2020 - March 2021) Lower progression (p=0.031) and faster improvement (p=0.013) c19early.org Holubovska et al., Advances in Respira.., May 2024 Favors enisamium Favors control

RNA Polymerase Inhibitor Enisamium for Treatment of Moderate COVID-19 Patients: A Randomized, Placebo-Controlled, Multicenter, Double-Blind Phase 3 Clinical Trial

Holubovska et al., Advances in Respiratory Medicine, doi:10.3390/arm92030021, NCT04682873
May 2024  
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RCT 592 hospitalized moderate COVID-19 patients in Ukraine showing improved recovery and lower progression with enisamium. The trial initially included patients with moderate COVID-19 not requiring oxygen, but a mid-trial change was made to exclude this group due to a lack of benefit, and results are reported for the patients requiring oxygen. The greatest benefit was seen in patients treated within 5 days of symptom onset.
risk of death, 85.7% lower, RR 0.14, p = 0.25, treatment 0 of 142 (0.0%), control 3 of 143 (2.1%), NNT 48, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), SR=4.
risk of progression, 74.8% lower, RR 0.25, p = 0.03, treatment 3 of 142 (2.1%), control 12 of 143 (8.4%), NNT 16, SR=4.
time to improvement, 9.1% lower, relative time 0.91, p = 0.01, treatment 142, control 143, SR=4, primary outcome.
risk of no hospital discharge, 88.9% lower, RR 0.11, p = 0.12, treatment 0 of 142 (0.0%), control 4 of 143 (2.8%), NNT 36, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), SR=4, day 29.
risk of no hospital discharge, 94.1% lower, RR 0.06, p = 0.007, treatment 0 of 142 (0.0%), control 8 of 143 (5.6%), NNT 18, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), SR=4, day 22.
risk of no hospital discharge, 60.8% lower, RR 0.39, p = 0.03, treatment 7 of 142 (4.9%), control 18 of 143 (12.6%), NNT 13, SR=4, day 15.
risk of no hospital discharge, 11.3% lower, RR 0.89, p = 0.23, treatment 81 of 142 (57.0%), control 92 of 143 (64.3%), NNT 14, SR=4, day 8.
risk of no viral clearance, 66.6% lower, RR 0.33, p = 1.00, treatment 0 of 142 (0.0%), control 1 of 143 (0.7%), NNT 143, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), SR=4, day 29.
risk of no viral clearance, 79.9% lower, RR 0.20, p = 0.50, treatment 0 of 142 (0.0%), control 2 of 143 (1.4%), NNT 72, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), SR=4, day 22.
risk of no viral clearance, 37.1% lower, RR 0.63, p = 0.57, treatment 5 of 142 (3.5%), control 8 of 143 (5.6%), NNT 48, SR=4, day 15.
risk of no viral clearance, 12.7% lower, RR 0.87, p = 0.40, treatment 52 of 142 (36.6%), control 60 of 143 (42.0%), NNT 19, SR=4, day 8.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Holubovska et al., 6 May 2024, Double Blind Randomized Controlled Trial, placebo-controlled, Ukraine, peer-reviewed, median age 59.0, 10 authors, study period 15 May, 2020 - 26 March, 2021, trial NCT04682873 (history). Contact: aj.te.velthuis@princeton.edu (corresponding author), ogolubovska@gmail.com, babich@gmail.com, miralla@ukr.net, milde@pharmalog.com, stammer@pharmalog.com, lebed@pharmaxi.com.ua, lutz.mueller@regenold.com, v.margitich@farmak.ua, a.goy@farmak.ua.
This PaperMiscellaneousAll
RNA Polymerase Inhibitor Enisamium for Treatment of Moderate COVID-19 Patients: A Randomized, Placebo-Controlled, Multicenter, Double-Blind Phase 3 Clinical Trial
Olga Holubovska, Pavlo Babich, Alla Mironenko, Jens Milde, Yuriy Lebed, Holger Stammer, Lutz Mueller, Aartjan J W Te Velthuis, Victor Margitich, Andrew Goy
Advances in Respiratory Medicine, doi:10.3390/arm92030021
Enisamium is an orally available therapeutic that inhibits influenza A virus and SARS-CoV-2 replication. We evaluated the clinical efficacy of enisamium treatment combined with standard care in adult, hospitalized patients with moderate COVID-19 requiring external oxygen. Hospitalized patients with laboratory-confirmed SARS-CoV-2 infection were randomly assigned to receive either enisamium (500 mg per dose, four times a day) or a placebo. The primary outcome was an improvement of at least two points on an eight-point severity rating (SR) scale within 29 days of randomization. We initially set out to study the effect of enisamium on patients with a baseline SR of 4 or 5. However, because the study was started early in the COVID-19 pandemic, and COVID-19 had been insufficiently studied at the start of our study, an interim analysis was performed alongside a conditional power analysis in order to ensure patient safety and assess whether the treatment was likely to be beneficial for one or both groups. Following this analysis, a beneficial effect was observed
randomization". We observed that on day 15, significantly fewer patients remained in the hospital in the enisamium-treated group compared to the placebo group (5.65% vs. 14.29%; one-sided p = 0.018) (Table 4 , Figure 4A ). On day 22, there were 0% hospitalized patients in the enisamium group compared to 6.3% in the placebo group (0.0% vs. 6.3%; one-sided p = 0.004).
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However, because the study was started ' 'early in the COVID-19 pandemic, and COVID-19 had been insufficiently studied at the start of ' 'our study, an interim analysis was performed alongside a conditional power analysis in order ' 'to ensure patient safety and assess whether the treatment was likely to be beneficial for one ' 'or both groups. Following this analysis, a beneficial effect was observed for patients with ' 'an SR of 4 only, i.e., patients with moderate COVID-19 requiring supplementary oxygen. The ' 'study was continued for these COVID-19 patients. Overall, a total of 592 patients were ' 'enrolled and randomized between May 2020 and March 2021. Patients with a baseline SR of 4 ' 'were divided into two groups: 142 (49.8%) were assigned to the enisamium group and 143 ' '(50.2%) to the placebo group. 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Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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