During the COVID-19 pandemic, Professor Porter’s team were busy trying to find alternative therapies for this new life-threatening Respiratory infection. Could a licenced drug that we already use be repurposed?
Presenting: “Nebulised dornase alfa reduces inflammation and improves clinical outcomes in severe COVID-19: a randomised clinical trial – The COVASE Study”
The COVASE study examined whether the cystic fibrosis drug, dornase alfa, could benefit hospitalised patients with COVID-19 pneumonia. In COVID-19 patients, cell-free DNA (cf-DNA) from various cellular sources, including Neutrophil Extracellular Traps (NETs), is present in the bloodstream and may contribute to immune system imbalances. This study aimed to investigate whether inhaling the enzyme dornase alfa could decrease inflammation by breaking down local and systemic cf-DNA.
Patients eligible for the study were randomly assigned (3:1) to receive dornase alfa through inhalation twice daily, in addition to the best available care (BAC), or BAC alone for seven days or until discharge. A group of matched contemporary controls (CC) at a 2:1 ratio was included for comparison. The primary goal was to assess the improvement in C-reactive protein (CRP) over time, analysed using a statistical model that considered baseline factors.
Between June 2020 and October 2021, 39 eligible patients were recruited: 30 received dornase alfa, 9 received BAC, and 60 were part of the CC group. Dornase alfa reduced CRP by 33% compared to BAC. Specifically, the average CRP levels dropped from 101.9mg/L to 23.23 mg/L in the BAC+dornase alfa group, while it fell from 99.5mg/L to 34.82 mg/L in the BAC group after 7 days (P=0.01). This effect was confirmed through various analyses. Dornase alfa increased the likelihood of a patient being discharged by 63%, boosted lymphocyte counts, and reduced circulating cf-DNA and the coagulopathy marker D-dimer. Dornase alfa was well-tolerated.
In summary, the COVASE study reached its primary endpoint, showing decreased CRP levels (inflammation marker), decreased oxygen requirements and reduced hospital stays from 11 to 5 days. Participants were found to have a 63% higher chance of surviving and leaving hospital, compared to patients receiving the best available care. This offers preliminary evidence that inhaling dornase alfa can reduce harmful inflammation in hospitalized COVID-19 pneumonia patients.
Professor Porter’s team who worked with Dr Papayannopoulos’ team from the Francis Crick Institute were awarded the Sir David Cooksey Prize in Translation for this clinical study. The scientific hypothesis for the study was generated in part from previous Breathing Matters important and ongoing work on neutrophils and extracellular traps.
The full article published in eLife can be found here. Awaiting information to see if this medication would be useful in ILD, especially in acute exacerbations.
[Posted 17/1/24; updated 22/7/24]