Tutorial presented by Dr Jon Underwood, Infectious Diseases and Acute Medicine Consultant

The main evidence for remdesivir in COVID-19 prior to the publication of the WHO’s SOLIDARITY trial (linked below) comes from the ACCT-1 trial (also linked below). In ACCT-1 remdesevir was associated with a shorter time to recovery overall, and the majority of the benefit was seen in patients who were on supplemental oxygen. The results of the SOLIDARITY trial and the associated meta-analysis have recently been published (after this video was made). Results from SOLIDARITY found remdesivir did not reduce the risk of death in the population treated, or in any subgroup of entry characteristics.

The totality of evidence however suggests that there may be a small treatment effect of remdesivir in hospitalised patients requiring oxygen, especially early in disease course. This benefit does not appear to extend to patients who are mechanically ventilated. This small effect size could be taken into account in individual patient decisions around initiation and discontinuation of treatment.

Remdesivir is indicated in patients who are:

• Hospitalised with coronavirus disease 2019 (COVID-19)
• Pneumonia requiring supplemental oxygen
• Adults, and adolescents ≥ 12 years of age and ≥ 40 kg
• eGFR ≥ 30ml/min
• Alanine Aminotransferase (ALT) below 5 times the upper limit of normal at baseline

The following criteria have been developed based on expert consensus and should be followed. A clinical pathway is presented which include steps, review points and actions outlined by these criteria.

Initiation of treatment

• The decision to initiate treatment with remdesivir should be made by the admitting consultant
• Remdesivir should not be initiated in patients who present to hospital more than 10 days after symptom onset.

Risk assessment

• Clinical judgement around treatment with remdesivir can be informed by a risk score. Those with a low 4C Mortality Score (0 to 3) are highly likely to recover without treatment with remdesivir.
• Remdesivir should not be initiated in patients who present to hospital and are unlikely to survive (determined by clinical judgment). The 4C Mortality Score might be helpful in this assessment.

Duration

• All patients must receive a maximum of 5 days of remdesivir in total (comprising a loading dose plus 4 further days of maintenance doses).

Reassessment and review

The use of remdesivir should be reassessed daily. Consider stopping remdesivir if:

• The patient clinically improves and no longer requires supplemental oxygen 72 hours after commencement of treatment; or
• The patient continues to deteriorate despite 48 hours of sustained mechanical ventilation.

Pregnancy

• Remdesivir should be avoided in pregnancy unless clinicians believe the benefits of treatment outweigh the risks to the individual (please see SmPC for further information). MDT discussion is advised.

Dose

• The recommended dosage is a single loading dose of remdesivir 200mg intravenously on day 1, followed by a once daily maintenance dose of remdesivir 100 mg for the remainder of the treatment course, which should not exceed five days.

Monitoring

• Renal and liver function should be monitored carefully during treatment with remdesivir as clinically appropriate.

Stopping criteria

Remdesivir should be discontinued in patients who develop any of the following:

• ALT ≥ 5 times the upper limit of normal during treatment with remdesivir (remdesivir may be restarted when ALT is < 5 times the upper limit of normal)
• ALT elevation accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or international normalised ratio (INR)
• eGFR <30 mL/min

The COVID-19 therapeutics advisory group recommends the use of remdesivir for patients on supplemental oxygen, and this can be seen in the flow chart linked below.