Compassionate Use Trial Inadequate to Demonstrate Efficacy of Remdesivir for COVID-19
The FLARE Four
- Remdesivir is a nucleoside analog that has shown in vitro activity against the novel coronavirus, SARS-CoV-2
- A recent New England Journal of Medicine paper reported the clinical course of 53 patients with COVID-19 who received remdesivir through compassionate use protocols
- This industry-sponsored study was uncontrolled and rife with methodological problems
- Ongoing randomized, clinical trials will provide information about the efficacy and safety of remdesivir in COVID-19
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Remdesivir, a nucleoside analog that inhibits RNA polymerases, has shown in vitro activity against the novel coronavirus, SARS-CoV-2, and is a plausible therapy for infected patients. However, a recently published report in the New England Journal of Medicine on compassionate use of remdesivir is an unsuitable guide to clinical decision-making, according to a fast literature update posted by the FLARE team at Massachusetts General Hospital on April 16, 2020.
Study Design
Intravenous remdesivir was provided to 53 patients with confirmed SARS-CoV-2 infection who had:
- Oxygen saturation ≤94% on room air or while receiving supplemental oxygen
- Creatinine clearance >30 mL/min
- Aspartate and alanine aminotransferase <5x the upper limit of normal
All patients received 200 mg remdesivir on day 1, then 100 mg/day for nine days. They were followed for at least 28 days or until discharge or death.
Efficacy
36 patients (68%) had an improvement in oxygen-support class:
- All 12 of those on room air or low-flow supplemental oxygen
- Five of seven on high-flow nasal oxygen or noninvasive positive-pressure ventilation
- Seventeen of 30 on mechanical ventilation (extubated)
- Three of four on extracorporeal membrane oxygenation (stopped receiving)
By the date of the most recent follow-up, seven patients had died (13%).
Adverse Events
The most common adverse events (AEs) were hepatic enzyme elevation (23%), diarrhea (9%), rash (8%), renal impairment (8%) and hypotension (8%). Twelve patients had serious AEs.
Critique
This report does not provide meaningful information about remdesivir because:
- It was industry-sponsored, non-randomized and uncontrolled
- Patients received variable courses of treatment, usually starting late in the infection (median duration of symptoms before initiation of remdesivir was 12 days)
- No information is provided about how remdesivir affected viral load or why patients were selected or rejected after applying for compassionate use
The FLARE team looks forward to results from the ongoing randomized, placebo-controlled trials of remdesivir.
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