Results from remdesivir compassionate use study for severe COVID-19

1. In this study, nearly 70% of patients who received remdesivir for compassionate use had an improvement in oxygen-support class and over half of intubated patients were able to be extubated.

2. As there was no control arm to the study, it is difficult to determine the true efficacy of remdesivir.

Evidence Rating Level: 3 (Average)

Study Rundown: The severity of symptoms of COVID-19 varies widely, but SARS-nCov-2 infection can quickly lead to life-threatening complications including acute respiratory distress syndrome and multisystem organ failure. Because there is currently no definitive treatment, disease management is limited to supportive care, such as supplemental oxygen and antibiotics, and experimental therapies including retroviral agents, antiinflammatory compounds, and convalescent plasma. Remdesivir is a broad-spectrum nucleotide analog prodrug that has shown in vitro activity against SARS-nCov-2 as well as a favorable clinical safety profile in patients treated for acute Ebola virus infection. In this study, remdesivir was provided on a compassionate-use basis to patients hospitalized with severe COVID-19, and incidence of key clinical events were tracked for four weeks. By the end of the trial, nearly 70% of patients showed an improvement in degree of oxygen support, and the majority of patients who were receiving invasive mechanical ventilation were extubated. These findings were independent of sex, comorbidities, and duration of symptoms before initiation of treatment. Over half of the patients experienced adverse events, and over a tenth died despite remdesivir treatment. This study had several limitations including the small size of the cohort, low patient retention, and the lack of both a control group and prespecified endpoints. Although the results are promising, larger-scale randomized controlled trials will offer stronger evidence regarding the use of remdesivir to treat patients with COVID-19.

Click here to read the study in NEJM

Relevant Reading: Covid-19 — The Search for Effective Therapy

In-Depth [prospective cohort]: In this multinational compassionate-use study, 61 patients were approved by Gilead Sciences to receive a 10-day course of remdesivir, consisting of a loading dose of 200 mg intravenously on the first day and 100 mg daily for the remaining 9 days. Eligibility criteria included hospitalization with reverse-transcriptase polymerase chain reaction (RT-PCR) confirmed SARS-nCov-2 infection in addition to either an oxygen saturation of 94% or less on ambient air or a need for oxygen support. Patients were not permitted to use other investigational agents during the trial. 8 patients who received the initial dose were excluded from final analyses due to missing postbaseline information. Of the 53 remaining patients, 10 received 5 to 9 days of treatment and 3 received fewer than 5 days. 36 patients (68%) showed an improvement in oxygen support class while 8 (15%) showed worsening. 17 of 30 (57%) patients who were originally receiving invasive ventilation were extubated, and 3 of 4 who were receiving extracorporeal membrane oxygenation were able to be removed. The cumulative incidence of clinical improvement, defined as live discharge or a decrease of at least 2 points on a 6 point ordinal scale, was 84% (95% confidence interval [CI], 70 to 99), but clinical improvement was less frequent among older patients as well as those receiving invasive mechanical ventilation. 60% of patients reported adverse events, the most common being increased hepatic enzymes, diarrhea, rash, renal impairment, and hypotension, and 23% of patients experienced serious adverse events. Overall mortality was 0.56 per 100 hospitalization days (95% CI, 0.14 to 0.97).

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