Dornase alfa to reduce hyperinflammation in COVID19 - The COVASE trial [COVID-19]
Research type
Research Study
Full title
A single-site, randomised, controlled, parallel design, open-label investigation of an approved nebulised recombinant human DNase enzyme (dornase alfa) to reduce hyperinflammation in hospitalised participants with COVID-19 (The COVASE trial)\n
IRAS ID
283091
Contact name
Joanna Porter
Contact email
Sponsor organisation
University College London
Eudract number
2020-001937-11
Clinicaltrials.gov Identifier
Data protection number , Z6364106/2020/04/70
Duration of Study in the UK
0 years, 3 months, 1 days
Research summary
Summary of Research
COVID-19 is caused by a type of virus called SARS-CoV-2, or coronavirus for short. About 8 out of 10 patients who get coronavirus get better without coming to hospital. Of those who are admitted to hospital, most also get better, but some may need oxygen or mechanical ventilation before they do so. However, a few percent do not get better. There are no drugs of proven value against COVID-19. Patients with excessive inflammation in response to COVID-19 infection, are at increased risk of needing oxygen or mechanical ventilation. This study aims to find out whether a treatment called Dornase Alfa may reduce the inflammation in patients with COVID-19 infection. We can measure the degree of inflammation in patients using a simple and routinely available blood tests that measures C-reactive protein (CRP) levels in the blood. CRP is normally less than 0.5mg/dL but in COVID-19 it can rise to be over 50 and in some cases over 300. This study aims to look at whether treatment with Dornase Alfa may reduce inflammation in patients with COVID-19 and a high CRP (above 30 g/dL). Dornase Alfa is a medication that has been used for many years to treat patients with Cystic Fibrosis. It is very safe, with very few side-effects, and is given as an inhaled treatment through a nebuliser twice a day for 7 days, or until patients leave hospital if they leave before the 7 days. The treatment will be given in addition to usual care. The aim of the study is to see if Dornase Alfa can reduce CRP back to normal levels in patients with COVID-19. We will also look at whether Dornase Alfa is able to speed up patients recovery and prevent them deteriorating and needing mechanical ventilation.Summary of Results
Efficacy Results:
The COVASE study met its primary endpoint to show a reduction in CRP (C-reactive protein) due to administration of dornase alfa for 7 days in participants hospitalised for COVID-19. This reduction was robust, as it was consistently observed in all sensitivity analyses, including stratification by type of BAC (best available care) received.
Several important secondary endpoints also showed statistically significant effects of dornase alfa.
A time-to-event analysis of baseline to discharge from hospital showed a 63% greater chance of discharge from hospital at any given time over 35 days follow-up in the dornase alfa group (p = 0.03) compared to the BAC group, and a median time to discharge of 6 days in the dornase alfa group compared to 7 days in the BAC group. This result was supported by non-significant trends in other endpoints related to hospitalisation (for example length of hospitalisation).
Dornase alfa had no detectable effect on any endpoint related to ICU (length of stay over 7 and 35 days; proportion of participants admitted to ICU during 7 and 35 day of follow-up).
Dornase alfa treatment resulted in a significant increase in blood lymphocyte count and a significant decrease in PCT and d-dimer.
Dornase alfa had no detectable effect on WHO ordinal scale, survival, mechanical ventilation or the proportion of participants with secondary bacterial pneumonia.Safety Results:
Dornase alfa was safe and well-tolerated. Adverse events were unremarkable and no treatment-related SAEs (serious adverse events) were detected.Conclusion:
In conclusion, dornase alfa treatment resulted in a significant reduction in CRP. This effect was supported by significant clinical effects on a selection of secondary endpoints, including hospitalisation, differential blood count (specifically lymphocytes) and relevant biomarkers, procalcitonin and d-dimer. Dornase alfa was safe and well-tolerated in hospitalised COVID-19 participants. These data may be used to optimally design a subsequent efficacy trial of dornase alfa in COVID-19.REC name
South Central - Hampshire B Research Ethics Committee
REC reference
20/SC/0197
Date of REC Opinion
30 Apr 2020
REC opinion
Further Information Favourable Opinion