A brief review of antiviral drugs evaluated in registered clinical trials for COVID-19

Abstract

BackgroundAlthough a number of antiviral agents have been evaluated for coronaviruses there are no approved drugs available. To provide an overview of the landscape of therapeutic research for COVID-19, we conducted a review of registered clinical trials. MethodsA review of currently registered clinical trials was performed on registries, including the Chinese (chictr.org.cn) and US (clinicaltrials.gov) databases to identify relevant studies up to March, 7 th 2020. FindingsOut of the 353 studies identified, 115 clinical trials were selected for data extraction. Phase IV trials were the most commonly reported study type (n=27, 23%). However, 62 trials (54%) did not describe the phase of the study. Eighty percent (n=92) of the trials were randomized with parallel assignment and the median number of planned inclusions was 63 (IQR, 36-120). Open-label studies were the most frequent (46%) followed by double-blind (13%) and single blind studies (10%). The most frequently assessed therapies were: stem cells therapy (n=23 trials), lopinavir/ritonavir (n=15), chloroquine (n=11), umifenovir (n=7), hydroxychloroquine (n=7), plasma treatment (n=7), favipiravir (n=7), methylprednisolone (n=5), and remdesivir (n=5). Remdesivir was tested in 5 trials with a median of 400 (IQR, 394-453) planned inclusions per trial, while stem cells therapy was tested in 23 trials, but had a median of 40 (IQR, 23-60) planned inclusions per trial. Lopinavir/ritonavir was associated with the highest total number of planned inclusions (2606) followed by remdesivir (2155). Only 52% of the clinical trials reported the treatment dose (n=60) and only 34% (n=39) the duration. The primary outcome was clinical in 76 studies (66%), virological in 27 (23%); radiological in 9 (8%) or immunological in three studies (3%). InterpretationNumerous clinical trials have been registered since the beginning of the COVID-19 outbreak, however, a number of information regarding drugs or trial design were lacking.

Type 1 interferons as a potential treatment against COVID-19

“…Antiviral treatments are warranted to contain the epidemics. Several candidates are already being investigated, including type 1 interferon (IFN-I) (Martinez, 2020;Belhadi et al, 2020). Indeed, in the context of emerging viral infections, IFN-I are often evaluated (usually in combination with other drugs) before specific treatments are developed, due to their unspecific antiviral effects (Gao et al, 2010;Loutfy et al, 2003;Omrani et al, 2014).…”

COVID-19 and the Gut Microbiome: More than a Gut Feeling

“…These strategies include remdesivir (Gilead Sciences), a nucleoside analogue that inhibits SARS-CoV-2 RNA-dependent RNA polymerase activity and viral replication ( 3 ), immune inhibitors, like the KEVZARA trial in which the efficacy of an anti-interleukin 6 (IL-6) receptor antibody is evaluated to stop an overactive inflammatory response, and development of monoclonal antibodies as therapy, as well as ongoing efforts with immediately available convalescent plasma ( 4 ). Also, type 1 interferons (especially alpha interferon [IFN-α] and IFN-β) with broad antiviral activity are being evaluated in clinical trials to treat SARS-CoV-2 ( 5 , 6 ). In vitro studies successfully confirmed the sensitivity of SARS-CoV-2 to type 1 interferons ( 7 ).…”

<p>The Current Recommended Drugs and Strategies for the Treatment of Coronavirus Disease (COVID-19)</p>

“…While the remdesivir was associated with the highest median number of the planned inclusions per trial (400, IQR 394-453) only for 5 trials. [15][16][17] Zhang et al 18 considered 125 clinical trials on the treatment of COVID-19, registered up to February 18, 2020, which were conducted by pharmaceutical companies, government, institutions, physicians, and scientists. Accordingly, the results showed that 33.3% of all the clinical trials used anti-viral agents, 14.7% antiinflammation or immune modulators, 33.3% herbs or traditional Chinese medicine (TCM), 9.3% cell-based therapy, 2.3% anti-oxidation, and 7.0% of them used other methods.…”