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27 april 2020

Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial - The Lancet

Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial - The Lancet

29-4-2020; https://marlin-prod.literatumonline.com/pb-assets/Lancet/pdfs/S0140673620310229.pdf
By: Wang, et al.

Aim: Investigate the effectiveness of 10 days IV remdesivir in patients with severe COVID-19 in a placebo-controlled, double-blind trial RCT

Keys:

  • IV remdesivir did not provide significant clinical or antiviral effects in seriously ill covid-19 patients

Summary:

  • Although several approved drugs and investigational agents have shown antiviral activity against SARS-CoV-2 in vitro at present there are no antiviral therapies of proven effectiveness in treating severely ill patient
  • Inclusion: patients > 18 years old with pCR proven covid-19 who had chest imaging proven pneumonia, a saturation of < 94% room air or <300mmHG arterial oxygen pressure and were within 12 days of symptom onset in 10 Wuhan Hospitals.

     

    • Pregnancy, renal / hepatic impairment were exclusion criteria
  • Primary endpoint was 2 point reduction in:

     

    • death=6; hospital admission for extracorporeal membrane oxygenation or mechanical ventilation=5; hospital admission for noninvasive ventilation or high-flow oxygen therapy=4; hospital admission for oxygen therapy (but not requiring high-flow or non-invasive ventilation)=3; hospital admission but not requiring oxygen therapy=2; and discharged or having reached discharge criteria
  • 236 patients included from 6-2 to 12-3. 158 remdesivir group, 79 placebo (2:1 randomisation).
  • Most patients were in category 3 of the six-point ordinal scale of clinical status at baseline. Some imbalances existed at enrolment between the groups, including more patients with hypertension, diabetes, or coronary artery disease in the remdesivir group than the placebo group. More patients in the control group than in the remdesivir group had been symptomatic for 10 days or less at the time of starting remdesivir or placebo treatment, and a higher proportion of remdesivir recipients had a respiratory rate of more than 24 breaths per min.
  • No differences in other received therapies between groups
  • In intention to treat and per-protocol analyses time to improvement was similar between groups.
  • 28-day mortality was similar between the two groups (14% vs 13%)
  • Duration of mechanical ventilation was similar
  • No significant differences were observed between the two groups in length of oxygen support, hospital length of stay, days from randomisation to discharge, days from randomisation to death.
  • Viral load decreased similarly over time in both groups.
  • Adverse events were reported in 102 (66%) of 155 patients in the remdesivir group and 50 (64%) of 78 in the control group. The most common adverse events in the remdesivir group were constipation, hypoalbuminaemia, hypokalaemia, anaemia, thrombocytopenia, and increased total bilirubin; and in the placebo group, the most common were hypoalbuminaemia, constipation, anaemia, hypokalaemia, increased aspartate aminotransferase, increased blood lipids, and increased total bilirubin.
  • 28 (18%) serious adverse events were reported in the remdesivir group and 20 (26%) were reported in the control group.
  • More patients in the remdesivir group than the placebo group discontinued the study drug because of adverse events or serious adverse events (18 [12%] in the remdesivir group vs four [5%] in the placebo group)
 

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