A Phase 2 interventional study of Dornase Alfa Inhalation Solution [Pulmozyme] in COVID-19 (Coronavirus Disease 2019) and Hypoxia, sponsored by University College, London. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2025-01-13.
Sponsored by University College, London · Phase 2, Interventional, and Treatment
An open-label, randomised, Best-Available-Care (BAC) and historic-controlled trial of nebulised dornase alfa [2.5 mg BID (bis in die)] for 7 days in participants with COVID-19 who are admitted to hospital and are at risk of ventilatory failure (the COVASE study). Controls will include a randomised arm to receive BAC, historic data from University College London Hospitals NHS Foundation Trust (UCLH) patients with COVID-19 and biobanked samples will be used to demonstrate an effect of dornase alfa. C-reactive protein (CRP) will be measured to assess the effect of dornase alfa on inflammation. Clinical endpoints and biomarkers (e.g. d-dimer) will be used to assess the clinical response. Exploratory endpoints will explore the effects of dornase alfa on features of neutrophil extracellular traps (NETs).
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 (tumour necrosis factor alpha) 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 (United Kingdom) and prevent ICU (intensive care unit) 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 2a 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.
7,638 studies on the registry are indexed under COVID-19; 488 are open to participants now.
This study's enrollment of 41 is below the median of 100 across 4,098 interventional studies indexed under COVID-19.
Browse COVID-19 studies →University College, London is the lead sponsor of 632 studies on the registry; 145 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 2 (33%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Serious condition meeting one of the following:
I. respiratory distress with respiratory rate >=40 breaths/min II. oxygen saturation \<=93% on high-flow oxygen
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]
Best available standard of care
Nebulised Dornase alfa 2.5mg bd for 7 days
Measuring the Change in Inflammation
Analysing stabilisation of C-reactive protein.
Time frame: 7 days
Survival at 35 Days
Survival at 35 days (28 days post last treatment day) Participants were followed up until discharge or death or a maximum of 28 days post last treatment day.
Time frame: 35 days
Discharge Before 35 Days
Number of participants discharged before 35 days
Time frame: Before 35 days
D-dimer (ug/L)
Change in D-dimer (ug/L) The reported LS means are antilogs of the LS means estimated on the log scale.
Time frame: 7 days
Lymphocyte Count (×109/L)
measure of Lymphocyte count (×109/L)
Time frame: 7 days
Recruited from acute COVID-19 (Coronavirus Disease 2019) wards between between May 2020-October 2021
| Milestone | Dornase Alfa Treatment | Best Available Care |
|---|---|---|
| Started | 31 | 10 |
| Completed | 30 | 9 |
| Not completed | 1 | 1 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Withdrew: Adverse event | 0 | 1 |
Analysing stabilisation of C-reactive protein.
| mg/L | Dornase Alfa Treatment | Best Available Care (Randomised) |
|---|---|---|
| Measuring the Change in Inflammation | 23.23 (17.71 to 30.46) | 34.82 (28.55 to 42.47) |
Survival at 35 days (28 days post last treatment day) Participants were followed up until discharge or death or a maximum of 28 days post last treatment day.
| Participants | Dornase Alfa Treatment | Best Available Care (Randomised) |
|---|---|---|
| Survival at 35 Days | 29 | 9 |
Number of participants discharged before 35 days
| Participants | Dornase Alfa Treatment | Best Available Care |
|---|---|---|
| Discharge Before 35 Days | 27 | 8 |
Change in D-dimer (ug/L) The reported LS means are antilogs of the LS means estimated on the log scale.
| (ug/L) FEU | Dornase Alfa Treatment | Best Available Care (Randomised) |
|---|---|---|
| D-dimer (ug/L) | 570.78 (384.51 to 847.3) | 1656.96 (876.93 to 3130.81) |
measure of Lymphocyte count (×109/L)
| ×10^9 cells/L | Dornase Alfa Treatment | Best Available Care (Randomised) |
|---|---|---|
| Lymphocyte Count (×109/L) | 1.08 (0.92 to 1.27) | 0.87 (0.76 to 0.98) |
Collected over 35 days or discharge whichever was sooner. Non-serious events are listed at a 2.5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dornase Alfa Treatment | 1/30 (3.3%) | 8/30 (26.7%) | 16/30 (53.3%) |
| Best Available Care | 0/9 (0%) | 2/9 (22.2%) | 4/9 (44.4%) |
| Event | Dornase Alfa Treatment | Best Available Care |
|---|---|---|
| Respiratory failure type 1Respiratory, thoracic and mediastinal disorders | 4/30 | 0/9 |
| Subdural haematomaInjury, poisoning and procedural complications | 0/30 | 1/9 |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 2/30 | 1/9 |
| Pulmonary hypertensionRespiratory, thoracic and mediastinal disorders | 0/30 | 1/9 |
| Aspiration pneumoniaInfections and infestations | 0/30 | 1/9 |
| Respiratory failure type 2Respiratory, thoracic and mediastinal disorders | 1/30 | 0/9 |
| Respiratory distressRespiratory, thoracic and mediastinal disorders | 1/30 | 0/9 |
| Organising pneumoniaRespiratory, thoracic and mediastinal disorders | 1/30 | 0/9 |
| PyelonephritisInfections and infestations | 1/30 | 0/9 |
| Hospital acquired pneumoniaInfections and infestations | 1/30 | 0/9 |
| Event | Dornase Alfa Treatment | Best Available Care |
|---|---|---|
| Dry noseRespiratory, thoracic and mediastinal disorders | 0/30 | 1/9 |
| EmphysemaRespiratory, thoracic and mediastinal disorders | 0/30 | 1/9 |
| Confusion aggravatedPsychiatric disorders | 0/30 | 1/9 |
| Oxygen saturation decreasedInvestigations | 0/30 | 1/9 |
| Blood in stoolGastrointestinal disorders | 0/30 | 1/9 |
| ConstipationGastrointestinal disorders | 1/30 | 1/9 |
| DiarrhoeaGastrointestinal disorders | 0/30 | 1/9 |
| Dry mouthGastrointestinal disorders | 0/30 | 1/9 |
| HaemorrhoidsGastrointestinal disorders | 0/30 | 1/9 |
| Chest painGeneral disorders | 3/30 | 0/9 |
| Age, Continuous(years) | Dornase Alfa Treatment | Best Available Care | Total |
|---|---|---|---|
| Mean | 56.8 ± 12.5 | 53.3 ± 13.7 | 56.8 ± 13.7 |
| Sex: Female, Male(Participants) | Dornase Alfa Treatment | Best Available Care | Total |
|---|---|---|---|
| Female | 7 | 2 | 9 |
| Male | 23 | 7 | 30 |
| Race and Ethnicity Not Collected(Participants) | Dornase Alfa Treatment | Best Available Care | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| C-reactive protein(mg/L) | Dornase Alfa Treatment | Best Available Care | Total |
|---|---|---|---|
| Mean | 101.9 ± 52.2 | 91.9 ± 68.1 | 100.2 ± 63.3 |
| Co-morbidities(Participants) | Dornase Alfa Treatment | Best Available Care | Total |
|---|---|---|---|
| Count of participants | 14 | 6 | 20 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No — Anonymised results will be published in a scientific journal (TBC) and posted on the Breathing Matters website www.breathingatters@ucl.ac.uk
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