Nebulised Dornase Alfa for Treatment of COVID-19 (COVASE)
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|ClinicalTrials.gov Identifier: NCT04359654|
Recruitment Status : Not yet recruiting
First Posted : April 24, 2020
Last Update Posted : April 30, 2020
|Condition or disease||Intervention/treatment||Phase|
|COVID19 Hypoxia||Drug: Dornase Alfa Inhalation Solution [Pulmozyme]||Phase 2|
Dornase alfa is a recombinant human DNase enzyme indicated in conjunction with standard therapies for the management of cystic fibrosis (CF) to improve pulmonary function. Dornase alfa degrades extracellular DNA, and so promotes the clearance of NETs and lead to a significant improvement in lung function for treated CF patients by facilitating mucus clearance in the lung. Dornase alfa is approved worldwide as a nebulised formulation, with an excellent safety profile and is well tolerated. The most common side effect is a hoarse voice. Moreover, dornase alfa could be administered in addition to effective antiviral therapy and should not interfere with antiviral drugs that could be used for COVID-19.
By facilitating the clearance of NETs, dornase alfa not only facilitates sputum clearance in CF patients, but has additional anti-inflammatory activity. Dornase alfa has been shown to reduce NETs in the bronchoalveolar lavage (BAL) and sputum of participants with CF (Konstan et al 2012). In the Bronchoalveolar Lavage for the Evaluation of Anti-inflammatory Treatment (BEAT) study, the percentage of neutrophils in bronchoalveolar lavage fluid significantly increased in untreated CF patients (P<0.02) while remaining constant in the dornase alfa-treated group. Levels of elastase and IL-8 also significantly increased from baseline in the untreated group (P<0.007 and P<0.02 for elastase and IL-8, respectively), but remained stable in patients receiving dornase alfa (Konstan and Ratjen, J. Cyst. Fibros. 2012).
There is scientific evidence to support the potential benefits of dornase alfa in COVID-19 infection. Viral sepsis driven by a hyperinflammation is thought to be a major cause of mortality in COVID-19 infection. Interleukin-1β (IL-1β), IL-6 and TNFα are key cytokines in microbial sepsis. Positive outcomes with Roche's Actemra (tocilizumab), an antibody that blocks the pro-inflammatory cytokine interleukin-6 (IL-6), in COVID-19 treatment has led to several anti-inflammatory trials.
Our hypothesis is that nebulised dornase alfa will break down the DNA backbone of NETs in the COVID-19 lung which will promote the degradation of pro-inflammatory extracellular histones and prevent the amplification of the inflammatory response and the resultant lung damage.
Positive data will enable rapid testing into a large clinical trial in the UK and prevent ICU capacity issues faced today. Dornase alfa is a cost-effective drug and is currently available for prescription.
We propose to test this hypothesis with this COVASE Phase IIa trial. We propose that all people with COVID-19 who are admitted to hospital for supplementary oxygen, who showed evidence of systemic inflammation but did not immediately require intubation and ventilation, would be eligible for nebulised dornase alfa, a safe and cost-effective treatment, twice daily for 7 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||An open-label, randomised, Best-Available-Care (BAC) and historic-controlled trial of nebulised dornase alfa [2.5 mg BID] for 7 days in participants with COVID-19 who are admitted to hospital and are at risk of ventilatory failure|
|Masking:||None (Open Label)|
|Official 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|
|Estimated Study Start Date :||May 1, 2020|
|Estimated Primary Completion Date :||August 1, 2020|
|Estimated Study Completion Date :||November 1, 2020|
Experimental: Dornase alfa treatment
Best available care and nebulised dornase alfa [2.5 mg BID] for 7 days in participants with COVID-19 who are admitted to hospital and are at risk of ventilatory failure
Drug: Dornase Alfa Inhalation Solution [Pulmozyme]
Nebulised Dornase alfa 2.5mg bd for 7 days
No Intervention: Best available care
Best available standard of care
- Measuring the change in inflammation [ Time Frame: 7 days ]Analysing stabilisation of C-reactive protein
- Number of patients that are alive at 28 days [ Time Frame: 28 days ]How many patients that are still alive
- Amount of days that patient requires oxygen [ Time Frame: 7 days ]How many days on oxygen
- Average oxygenation index [ Time Frame: 7 days ]Calculating index with Fi02, mean airways pressure and Pa02 via https://www.mdcalc.com/oxygenation-index#use-cases
- Days patient admitted to hospital [ Time Frame: 7 days ]How many days as an inpatient
- Percentage of patients that need mechanical ventilation [ Time Frame: 7 days ]How many patients require mechanical ventilation
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04359654
|Contact: Misha Ladva||0044 20 3108 firstname.lastname@example.org|
|Contact: Novin Fard||0044 20 3447 email@example.com|
|Principal Investigator:||Joanna Porter, MD PhD||University College, London|