Use of remdesivir in COVID-19 patients requiring respiratory support confers no benefit over standard care

Study finds use of remdesivir in COVID-19 patients needing respiratory support offers no benefit over standard care

Use of remdesivir in patients hospitalized with COVID-19 requiring ventilator or oxygen support did not improve clinical outcomes after 15 days compared to standard care. This is the conclusion of a European, multicenter, open, randomized and controlled trial.

Remdesivir is a prodrug that converts into nucleoside analog and incorporated by COVID-19 RNA-dependent RNA polymerase into growing RNA product before RNA synthesis stops. The drug was approved by the EMA in June 2020 for the treatment of COVID-19 in adults and adolescents from 12 years of age with pneumonia who require supplemental oxygen. Additionally, early data on remdesivir was encouraging and in a study of over 1,000 patients, those randomized to use remdesivir had a median recovery time of 10 days compared to 15 days in those who received a placebo. In contrast, however, the World Health Organization (WHO) Solidarity Trial concluded that remdesivir, as well as hydroxychloroquine, lopinavir and interferon-based regimens, had little or no effect on hospitalized patients with COVID-19, as indicated by overall mortality, initiation of ventilation, and length of hospital stay.

With such contradictory results, the European team undertook the DisCoVery trial and which was designed to assess the safety and efficacy of possible therapeutic agents in hospitalized adult patients diagnosed with COVID-19. Patients recruited were adults hospitalized with COVID-19 who had evidence of rales/crackles on examination and SpO2

Remdesivir use and clinical outcomes

A total of 857 participants with a median age of 64 years (69.5% male) were randomized to receive remdesivir (420) or standard care and, at randomization, 39.4% of individuals had severe COVID-19.

Overall, 73.6% of participants had at least one comorbidity, the most common being obesity (34.1%), heart disease (28%) and diabetes (27%).

At day 15, a similar proportion of those assigned to remdesivir and standard care were classified as category 1 on the WHO scale (14.8% versus 17%, remdesivir versus standard care) and a similar proportion were deceased (5% versus 6%). Overall, there was no significant difference between those assigned to remdesivir use or standard care (odds ratio, OR = 1.02, 95% CI 0.62, 1.70, p = 0.93). Additionally, there were no significant differences in the distribution of the 7-point scale at day 29 (OR = 1.11, 95% CI 0.87 – 1.43, p = 0.40) .

Additionally, there were no significant differences for any of the secondary outcomes or subgroup analyzes by age, sex, duration of symptoms before randomization, or level of detectable viral loads at each sampling time.

The authors therefore concluded that the use of remdesivir had no impact on clinical outcomes compared to standard care at day 15 or day 29.

Quote
Ader F et al. Remdesivir for the treatment of hospitalized patients with COVID-19: final results from the randomized, controlled, open-label DisCoVery trial MedRxiv 2022