- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04359654
Nebulised Dornase Alfa for Treatment of COVID-19 (COVASE)
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
Study Overview
Status
Intervention / Treatment
Detailed Description
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
London, United Kingdom, NW1 2BU
- University College London Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male and female participants, aged ≥ 18 years.
- Participants who are hospitalised for suspected Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test or radiological confirmation.
- Participants with stable oxygen saturation (>=94%) on supplementary oxygen
- CRP >= 30 mg/L.
- Participants will have given their written informed consent to participate in the study and are able to comply with instructions and nebuliser.
Exclusion Criteria:
- Females who are pregnant, planning pregnancy or breastfeeding.
- Concurrent and/or recent involvement in other research or use of another experimental investigational medicinal product that is likely to interfere with the study medication within the last 3 months before study enrolment.
Serious condition meeting one of the following:
I. respiratory distress with respiratory rate >=40 breaths/min II. oxygen saturation <=93% on high-flow oxygen
- Require mechanical invasive or non-invasive ventilation at screening
- Concurrent severe respiratory disease such as asthma, COPD and/or ILD.
- Any major disorder that in the opinion of the Investigator would interfere with the evaluation of the results or constitute a health risk for the study participant.
- Terminal disease and life expectancy <12 months without COVID-19.
- Known allergies to the dornase alfa and excipients.
- Participants who are unable to inhale or exhale orally throughout the entire nebulisation period.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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
|
Nebulised Dornase alfa 2.5mg bd for 7 days
|
No Intervention: Best available care
Best available standard of care
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Measuring the change in inflammation
Time Frame: 7 days
|
Analysing stabilisation of C-reactive protein
|
7 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of patients that are alive at 28 days
Time Frame: 28 days
|
How many patients that are still alive
|
28 days
|
Amount of days that patient requires oxygen
Time Frame: 7 days
|
How many days on oxygen
|
7 days
|
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
|
7 days
|
Days patient admitted to hospital
Time Frame: 7 days
|
How many days as an inpatient
|
7 days
|
Percentage of patients that need mechanical ventilation
Time Frame: 7 days
|
How many patients require mechanical ventilation
|
7 days
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Joanna Porter, MD PhD, University College, London
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 132333
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hypoxia
-
Western University, CanadaUnknownBrain Hypoxia IschemiaCanada
-
Yale UniversityTianjin Chest HospitalCompletedBrain Ischemia Hypoxia | Muscle; Ischemic | Muscle HypoxiaChina
-
Fliegerärztliches InstitutCompleted
-
University of Texas at AustinCompletedIntermittent HypoxiaUnited States
-
Owlet Baby Care, Inc.Completed
-
Robert L. OwensCompletedIntermittent HypoxiaUnited States
-
University of Texas at AustinCompleted
-
Harbin Medical UniversityUnknown
-
University Hospital TuebingenUnknown
-
Montreal Heart InstituteUniversité de MontréalCompleted
Clinical Trials on Dornase Alfa Inhalation Solution [Pulmozyme]
-
University of Missouri-ColumbiaCompletedSARS-CoV 2 | ARDSUnited States
-
Fondation Ophtalmologique Adolphe de RothschildUniversity Hospital, Strasbourg, France; Centre Hospitalier Régional Metz-ThionvilleTerminatedCOVID-19 | Acute Respiratory Distress SyndromeFrance
-
Northwestern UniversityGenentech, Inc.UnknownHead and Neck CancerUnited States
-
Boston Children's HospitalBrigham and Women's Hospital; South Shore HospitalRecruiting
-
Genentech, Inc.Terminated
-
University of Colorado, DenverGenentech, Inc.CompletedOtitis MediaUnited States
-
Genentech, Inc.TerminatedCystic FibrosisUnited States
-
Genentech, Inc.Completed
-
University of JenaCompletedCystic Fibrosis | RhinosinusitisGermany
-
AO GENERIUMCompletedFibrosis | Cystic FibrosisRussian Federation