The content of this evidence review was up-to-date on 4 June 2020. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information. For details on the date the searches for evidence were conducted see the search strategy
COVID-19 manifests as a predominantly respiratory illness, of widely varying clinical severity. At the most severe end of the spectrum it results in severe pneumonia and respiratory failure with the need for mechanical ventilation. Acute respiratory distress syndrome (ARDS) is often a pre-terminal event in patients with COVID-19 and is the leading cause of mortality.
This is a rapidly evolving pandemic globally, with countries facing different stages of the spread of disease. Initial hospital data from the UK suggest that increasing age over 50 years is a strong predictor of mortality in hospital (hazard ratio [HR] 4.02 for 50–69 years, 9.6 for 70–79 years and 13.6 for 80 years or over; Docherty et al. 2020). Children and young people appear to be less affected by the virus, with low numbers of deaths and critical care admissions in this age group (Lu et al. 2020). UK primary care record data from 17.4 million patients showed death in hospital from COVID-19 was strongly associated with male gender, older age, Black or Asian ethnicity, deprivation, uncontrolled diabetes and severe asthma. Treatment options for COVID-19 are limited and there are trials underway to assess the efficacy of available medicines to manage the disease.
Remdesivir is an adenosine nucleotide prodrug that is metabolised intracellularly to form the pharmacologically active substrate remdesivir triphosphate. Remdesivir triphosphate inhibits SARS-CoV-2 RNA polymerase which prevents viral replication.
Remdesivir is the first COVID-19 treatment to receive a positive scientific opinion by the Medicines and Healthcare products Regulatory Agency (MHRA), based on advice from the Commission on Human medicines, under the rapid early access to medicines scheme (EAMS) by meeting the EAMS published access criteria. Remdesivir is indicated for the treatment of adults and young people aged 12 years and over and weighing at least 40 kg hospitalised with suspected or laboratory confirmed SARS-CoV-2 infection and severe disease.
This review aims to establish the clinical effectiveness, safety and cost effectiveness of remdesivir in adults, young people and children hospitalised with suspected or confirmed COVID-19.
The research questions are:
In adults, young people and children hospitalised with suspected or confirmed COVID-19 (COVID-19 is the acute clinical syndrome caused by SARS-CoV2 virus), what is the clinical effectiveness of remdesivir compared with placebo or standard care? (Standard care can vary according to country. In the UK standard care for COVID-19 is supportive treatment.)
In adults, young people and children hospitalised with suspected or confirmed COVID-19, what is the safety of remdesivir compared with placebo or standard care?
In adults, young people and children hospitalised with suspected or confirmed COVID-19, what is the cost effectiveness of remdesivir compared with lacebo or standard care?
From the evidence selected, are there any subgroups of patients that may benefit or be harmed from remdesivir more than the wider population of interest?
From the evidence selected:
what definitions have been used/developed to describe 'moderate' and 'severe' COVID-19?
what is the duration of remdesivir treatment?
Three studies identified from the search are included in this evidence summary. Two studies (Beigel et al. 2020 and Wang et al. 2020) are phase 3 double-blinded, placebo-controlled randomised controlled trials (RCT) and 1 study is an observational study (Grein et al. 2020). A meta-analysis of the 2 included RCTs (Cochrane 2020) was also identified following the search and included.
Remdesivir when compared with placebo was associated with clinical improvements in some of the outcomes and fewer serious adverse events.
The findings in the review suggest that factors to consider when using remdesivir as a treatment option for COVID-19 in patients with mild or moderate, or severe disease include the timing of initiation of treatment at the onset of symptoms, disease severity (this includes the need for oxygen support, non-invasive ventilation, invasive ventilation or organ support, most of the patients in the studies had severe COVID-19) and the underlying clinical status of the patient and age. These may have important effects on the outcomes of treatment. Remdesivir should only be administered by intravenous infusion which may limit its use.