Umifenovir in hospitalized moderate to severe COVID-19 patients: A randomized clinical trial

Abstract

Introduction The effectiveness of umifenovir against COVID-19 is controversial; therefore, clinical trials are crucial to evaluate its efficacy. Methods The study was conducted as a single-center, randomized, open-label clinical trial. Eligible moderate-severe hospitalized patients with confirmed SARS-Cov-2 infection were randomly segregated into intervention and control groups. The intervention group were treated with lopinavir/ritonavir (400 mg/100 mg bid for 10–14 days) + hydroxychloroquine (400 mg single dose) + interferon-β1a (Subcutaneous injections of 44 µg (12,000 IU) on days 1, 3, 5) + umifenovir (200 mg trice daily for 10 days), and the control group received lopinavir/ritonavir (same dose) + hydroxychloroquine (same dose) + interferon-β1a (same dose). Results Of 1180 patients with positive RT-PCRs and positive chest CT scans, 101 patients were finally included in the trial; 50 were assigned to receive IFNβ1a + hydroxychloroquine + lopinavir/ritonavir group and 51 were managed to treat with IFNβ1a + hydroxychloroquine + lopinavir/ritonavir + umifenovir. Since all patients received the intended treatment as scheduled, the analysis just included as the ITT population. Time to clinical improvement (TTCI) did not hold a statistically significant difference between intervention and control groups (median, 9 days for intervention group versus 7 days for the control group; P: 0.22). Besides, Hazard Ratio for TTCI in the Cox regression model was 0.75 (95% CI: 0.45–1.23, P:0.25) which also confirmed that there was no statistically significant difference between the treatment group and the control group. The mortality was not statistically significant between the two groups (38% in controls vs 33.3% treatment group). Conclusions Our findings shed new lights on the facts that additional umifenovir has not been found to be effective in shortening the duration of SARS-CoV-2 in severe patients and improving the prognosis in non-ICU patients and mortality. Trial registration The trial was confirmed by the Ethics in Medical Research Committee of the Shahid Beheshti University of Medical Sciences. signed informed consents were obtained from all the participants or their legally authorized representatives. This trial has been registered as ClinicalTrials.gov, NCT04350684.

Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials

“…One study was originally included, but was later retracted due to concerns about data integrity, and thus was excluded [ 42 ]. Antiviral treatments compared in the included studies were umifenovir (Arbidol) [ 25 , 29 , 31 , 47 ], baloxavir marboxil [ 30 ], enisamium [ 50 ], favipiravir [ 25 , 30 , 35 , 40 – 42 , 44 , 45 , 48 , 52 ], lopinavir/ritonavir (LPV/r) [ 24 , 26 , 27 , 29 , 31 , 37 , 38 , 44 , 47 ], remdesivir [ 23 , 34 , 36 , 39 , 51 , 53 ], ribavirin [ 22 ], sofosbuvir/daclatasvir [ 22 , 32 , 33 , 46 , 49 ], sofosbuvir/ledipasvir [ 28 ], sofosbuvir/ravidasvir [ 46 ], and sofosbuvir/velpatasvir [ 43 ]. The study characteristics and baseline patient characteristics are summarized in Table 2 .…”

Healthy Immunity on Preventive Medicine for Combating COVID-19

“…Both Remdesivir and Chloroquine received EUA by the FDA for treatment of COVID-19, and they, especially Remdesivir, were found to reduce COVID-19-related complications in certain age grouped people [ 19 , 20 ]. Similarly, Umifenovir was reported to have moderate effects in the management of severe COVID-19 infections [ 25 ]. Recently, Merck and Co., in collaboration with Ridgeback Therapeutics, have developed an antiviral oral drug, named Molnupiravir, for the treatment of COVID-19 patients, which shows promising effects against infections and reduces hospitalizations and fatal outcomes by 50%.…”

“…The pathophysiological manifestations of this disease include aberrant respiratory distress, hypoxia, lung injury, inflammation, and a cytokine storm [ 13 , 14 ]. Patients afflicted with COVID-19 display diverse conditions, ranging from asymptomatic to severe symptoms, which involve aging and age-related comorbidities; sex and gender differences; and underlying medical conditions such as cancers, diabetes, autoimmune and inherited diseases, and neurological disorders [ 25 , 37 , 160 ]. Importantly, geriatric populations, especially men in comparison to women, are radically affected by severe COVID-19 infections, along with mortalities ( Figure 4 ), underscoring the importance of a boosted immune health in the fundamental protection from this deadly disease.…”

“…Even so, the COVID-19 pandemic, impacting infections and mortalities worldwide, has prompted the development and urgent approval of a number of measures, including vaccinations and medications [ 17 , 18 ]. Currently, a few anti-viral drugs and antibody cocktails have received emergency use authorization (EUA) to respond to and/or treat certain COVID-19 patients to reduce hospitalizations, as well as mortalities [ 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Therapeutic strategies, targeting the prevention and treatment of COVID-19, require an improved understanding of the host–pathogen interacting mechanism(s), symptomatology, and disease pathogenesis.…”

Simulation of Molecular Dynamics of SARS-CoV-2 S-Protein in the Presence of Multiple Arbidol Molecules: Interactions and Binding Mode Insights

“…Moreover, a probable binding site located in the S1 subunit in the region of the fusion peptide (FP2) was also considered. Modern clinical trials have shown [39,40] that umifenovir monotherapy appears to be ineffective. However, we are considering Arbidol as a potential comparison drug because no other antiviral agents active in the early stages of viral replication are currently available.…”