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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'abstract': '<jats:p>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 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 '
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'improvement was 8 days for the enisamium group and 13 days for the placebo group (p = 0.005). '
'For patients treated within 10 days of the onset of COVID-19 symptoms (n = 154), the median '
'time to improvement was 10 days for the enisamium group and 12 days for the placebo group (p '
'= 0.002). Our findings suggest that enisamium is safe to use with COVID-19 patients, and that '
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'Hospitalised with COVID-19 during the First Pandemic Wave from the '
'ISARIC WHO CCP-UK Study: A Multicentre, Prospective Cohort Study',
'volume': '2',
'author': 'Russell',
'year': '2021',
'journal-title': 'Lancet Microbe'}],
'container-title': 'Advances in Respiratory Medicine',
'original-title': [],
'language': 'en',
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'deposited': { 'date-parts': [[2024, 5, 6]],
'date-time': '2024-05-06T20:35:20Z',
'timestamp': 1715027720000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.mdpi.com/2543-6031/92/3/21'}},
'subtitle': [],
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'issued': {'date-parts': [[2024, 5, 6]]},
'references-count': 31,
'journal-issue': {'issue': '3', 'published-online': {'date-parts': [[2024, 6]]}},
'alternative-id': ['arm92030021'],
'URL': 'http://dx.doi.org/10.3390/arm92030021',
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