COVID-19 Antivirals: Interim WHO Solidarity Trial Results Confirms That Remdesivir, Lopinavir And Interferon Have No Effect On COVID-19 Mortality
: The interim WHO Solidarity Trial results confirms that antivirals like remdesivir, lopinavir, interferon and hydroxychloroquine seem to have little to no effect on mortality for hospitalized patients with COVID-19.
The trial randomly assigned hospitalized patients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry.
The trial was conducted across 405 hospitals in 30 countries and a total of 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug.
Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P=0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P=0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P=0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P=0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration.
The study funded by the WHO on the whole showed that these four antivirals had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay.
The study results were published in the peer reviewed New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa2023184?query=featured_home
The earlier Recovery Drug Trial also by WHO also showed results that lopinavir and hydroxychloroquine did not have any efficacy to treat COVID-19.
Dr Hongchao Pan, Ph.D., from the University of Oxford in the United Kingdom, and colleagues examined in-hospital mortality in four pairwise comparisons of each of four trial drugs (remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a) and its control among inpatients with COVID-19.
The study found that at midway through treatment, adherence was 94 to 96 percent. In total, there were 1,253 deaths reported. The Kaplan-Meier 28-day mortality was 11.8 percent: 39.0 and 9.5 percent if the patient was or was not receiving ventilation at randomization, respectively. The r
ate ratios for deaths were 0.95 (95 percent confidence interval, 0.81 to 1.11; P = 0.50) for patients receiving remdesivir versus control; 1.19 (95 percent confidence interval, 0.89 to 1.59; P = 0.23) for patients receiving hydroxychloroquine versus control; 1.00 (95 percent confidence interval, 0.79 to 1.25; P = 0.97) for patients receiving lopinavir versus control; and 1.16 (95 percent confidence interval, 0.96 to 1.39; P = 0.11) for patients receiving interferon versus control. None of the trial drugs reduced in-hospital mortality, initiation of ventilation, or duration of hospitalization.
The study team commented, "The unpromising overall findings from the regimens tested suffice to refute early hopes, based on smaller or nonrandomized studies, that any of these regimens will substantially reduce inpatient mortality, the initiation of mechanical ventilation, or hospitalization duration.”
The COVID-19 pandemic is talking wreaking havoc across the globe with more than 65.8 million global cases of SARS-CoV-2 infection so far and more than 1.52 million deaths as a result of the disease and with daily infections now crossing the 600,000 mark and daily deaths crossing the 12,000 mark.
Researchers and scientist are desperate to find effective pharmaceuticals, repurposed drugs, herbs and phytochemicals that can treat the COVID-19 disease.There are currently lots of study trials underway exploring a variety of therapeutics to tyr to treat COVID-19.
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