COVID-19Phase 3COVIDORNASENCT04355364
Efficacy and Safety of aerosolizedDornase Alfa Administration in Patients With COVID19 Induced ARDS (COVIDORNASE)
A Phase 3 study testing Dornase Alfa Inhalation Solution [Pulmozyme] and standard procedure in people with COVID-19 and Acute Respiratory Distress Syndrome, run by Fondation Ophtalmologique Adolphe de Rothschild at 1 site in France.
Trial summary
This study plans to learn more about the effects of Dornase Alfa in COVID19 (coronavirus disease of 2019) patients, the medical condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19, Acute Respiratory Distress Syndrome
- What is being tested?
- Dornase Alfa Inhalation Solution [Pulmozyme] and standard procedure
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 1 siteFrance
- Study dates
- 21 Apr 2020to 20 Dec 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patient (age ≥ 18 years old);
- Hospitalized in intensive care ;
- Severe COVID-19 pneumonia (positive diagnosis by RT-PCR or SARS-CoV-2 antigen test on nasopharyngeal or deep respiratory specimen and/or evocative thoracic scan: frosted glass opacities, consolidation, cross-linking, thickening of interlobular septa, peripheral nodules) with ARDS criteria according to Berlin criteria (PaO2/FiO2 ≤ 300 and PEP ≥ 5).
- With respiratory assistance (intubated or NIV or ONHD) for less than 8 days;
- With an expected duration of respiratory assistance > 48 hours;
- Carrier of an arterial catheter ;
- For which 4 PaO2/FiO2 values on arterial blood over the last 24 hours are available;
Who cannot join
- Known hypersensitivity to Dornase alfa or any of the excipients;
- Pregnant or breastfeeding status;
- Patient with legal protection.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy and Safety of Dornase Alfa Aerosol in ARDS Secondary to SARS-CoV-2 Coronavirus Respiratory Infection - COVID-19
This study plans to learn more about the effects of Dornase Alfa in COVID19 (coronavirus disease of 2019) patients, the medical condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Dornase Alfa is a FDA-approved drug for the treatment of cystic fibrosis, which facilitates mucus clearance by cutting apart neutrophil-derived extracellular double-stranded DNA. This study intends to define the impact of aerosolized intra-tracheal Dornase Alfa administration on the severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19 patients. This drug might make lung mucus thinner and looser, promoting improved clearance of secretions and reduce extracellular double-stranded DNA-induced hyperinflammation in alveoli, preventing further damage to the lungs.
The study will recruit mechanically ventilated patients hospitalized in ICU who have been diagnosed with COVID-19 and meet ARDS criteria. It is a prospective, randomized, controlled, multicentric, open-label clinical trial.
The goal is to recruit 100 patients.
Read the detailed description
Acute Respiratory Distress Syndrome (ARDS) is the most severe form of COVID-19 with a mortality reaching 50%. To date, no specific therapy has been shown to be effective. During an acute viral respiratory infection, lungs are the site of an intense neutrophil recruitment. Recruited neutrophils generate NETs (extracellular neutrophil traps) in the alveoli and bronchioles. NETs have been shown to be involved in bronchoalveolar congestion and amplification of the inflammatory response during viral pneumonia responsible for ARDS. Deoxyribonuclease 1 (DNAse 1) is an enzyme capable of cutting apart extracellular DNA strands, the backbone of NETs. The administration of recombinant human DNAse 1 (dornase alfa) leads to the loosening of the broncho-alveolar mucus and to a reduction in the inflammatory response within the alveoli.
By conducting a randomized, open-label, multicenter, controlled trial, our goal is to evaluate the efficacy and safety of aerosolized intra-tracheal dornase alfa administration in mechanically ventilated patients hospitalized for COVID19-related ARDS.
This is a randomized, controlled, multicentric, open-label clinical trial to evaluate the efficacy and safety of dornase alfa administration aerosol, intensive care hospitalized patients with COVID19-related ARDS.
The comparison of D7-D0 between the groups will be carried out using a linear regression fitted to the stratification factors.
- Conditions
- COVID-19, Acute Respiratory Distress Syndrome
- Being tested
- Dornase Alfa Inhalation Solution [Pulmozyme], standard procedure
- Medical subject headings
- COVID-19, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dornase Alfa Inhalation Solution [Pulmozyme]Drug
Administered by nebulization, at a dose of 2500 IU twice daily, 12 hours apart, for 7 consecutive days
standard procedureProcedure or surgery
Patients will receive the usual care in accordance with good practice.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | Dornase alfa will be administered by nebulization, at a dose of 2500 IU twice daily, 12 hours apart, for 7 consecutive days, using a vibrating mesh nebulizer. The remainder of the management will be performed in accordance with good practice, including mechanical ventilation (protective ventilation, PEEP > 5 cmH2O, tracheal balloon pressure checking every 4 hours or automatic device, 30° head of the bed elevation, tidal volume 6-8mL/kg, plateau pressure < 30cmH2O), neuromuscular blockers if necessary, prone position if PaO2/FiO2<150, early enteral nutrition, glycemic control, a sedation protocol based on the RASS score. Receives: Drug: Dornase Alfa Inhalation Solution [Pulmozyme] |
| Control group | Active comparator | Patients will receive the usual care in accordance with good practice. Receives: Procedure: standard procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of intratracheal administration: occurrence of at least one grade improvement
The primary endpoint is the occurrence of at least one grade improvement between D0 (inclusion) and D7 in the ARDS scale severity (Berlin criteria). For instance from severe to moderate or from moderate to mild
Measured: Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2020
- Study start21 Apr 2020
- Primary completion20 Dec 2021
- Study completion20 Dec 2021
Why it stopped: No signal of benefit of treatment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Fondation Ophtalmologique Adolphe de RothschildThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Dornase alfa will be administered by nebulization, at a dose of 2500 IU twice daily, 12 hours apart, for 7 consecutive days, using a vibrating mesh nebulizer. The remainder of the management will be performed in accordance with good practice, including mechanical ventilation (protective ventilation, PEEP \> 5 cmH2O, tracheal balloon pressure checking every 4 hours or automatic device, 30° head of the bed elevation, tidal volume 6-8mL/kg, plateau pressure \< 30cmH2O), neuromuscular blockers if necessary, prone position if PaO2/FiO2\<150, early enteral nutrition, glycemic control, a sedation protocol based on the RASS score.tracheal balloon pressure checking every 4 hours or automatic device, 30° head of the bed elevation, tidal volume 6-8mL/kg, plateau pressure \< 30cmH2O), neuromuscular blockers if necessary, prone position if PaO2/FiO2\<150, early enteral nutrition, glycemic control, a sedation protocol based on the RASS score.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondation Ophtalmologique Adolphe de Rothschild
- Sponsor type
- Research network
- Collaborators
- University Hospital, Strasbourg, France, Centre Hospitalier Régional Metz-Thionville
- Responsible party
- Sponsor
- Investigators
- Charles Grégoire, MD, Principal investigator, Hôpital Fondation A de RothschildJulien Pottecher, MD, Study chair, CHRU StrasbourgFabien Lambiotte, MD, Study chair, CH VALENCIENNESSerge Le Tacon, MD, Study chair, CHR Metz-ThionvilleMarie-Reine Pr Losser, Study chair, CHRU NancyPierre Kalfon, MD, Study chair, CH ChartresVincent Das, MD, Study chair, CH MontreuilKarim Nourdine, MD, Study chair, Hôpital Drôme Nord
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04355364
- Sponsor's protocol ID
- CGE_2020_9
- Acronym
- COVIDORNASE
- Status last verified
- Dec 2021
- First submitted
- 15 Apr 2020
- Last updated
- 11 Jan 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gregoire C, Di Meglio L, Le Cossec C, Ho-Tin-Noe B, Nomenjanahary MS, Guillaume J, Hamdani M, Losser MR, Lambiotte F, Le Tacon S, Cantier M, Engrand N, Yavchitz A, Trouiller P, Desilles JP, Pottecher J. Multicenter randomized trial assessing efficacy and safety of aerosolized dornase Alfa in COVID-19 ARDS. Sci Rep. 2025 Oct 22;15(1):36876. doi: 10.1038/s41598-025-20832-x.
PubMed 41125713Desilles JP, Gregoire C, Le Cossec C, Lambert J, Mophawe O, Losser MR, Lambiotte F, Le Tacon S, Cantier M, Engrand N, Trouiller P, Pottecher J. Efficacy and safety of aerosolized intra-tracheal dornase alfa administration in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS): a structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 19;21(1):548. doi: 10.1186/s13063-020-04488-8.
PubMed 32560746
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Dornase Alfa Aerosol in ARDS Secondary to SARS-CoV-2 Coronavirus Respiratory Infection - COVID-19
- ClinicalTrials.gov ID
- NCT04355364
- Acronym / sponsor ID
- COVIDORNASE / CGE_2020_9
- Conditions
- COVID-19, Acute Respiratory Distress Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No signal of benefit of treatment.
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Fondation Ophtalmologique Adolphe de RothschildResearch network
- Collaborators
- University Hospital, Strasbourg, France, Centre Hospitalier Régional Metz-Thionville
- Study start
- 21 Apr 2020 (actual)
- Primary completion
- 20 Dec 2021 (actual)
- Study completion
- 20 Dec 2021 (actual)
- First posted
- 21 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study plans to learn more about the effects of Dornase Alfa in COVID19 (coronavirus disease of 2019) patients, the medical condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Dornase Alfa is a FDA-approved drug for the treatment of cystic fibrosis, which facilitates mucus clearance by cutting apart neutrophil-derived extracellular double-stranded DNA. This study intends to define the impact of aerosolized intra-tracheal Dornase Alfa administration on the severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19 patients. This drug might make lung mucus thinner and looser, promoting improved clearance of secretions and reduce extracellular double-stranded DNA-induced hyperinflammation in alveoli, preventing further damage to the lungs.
The study will recruit mechanically ventilated patients hospitalized in ICU who have been diagnosed with COVID-19 and meet ARDS criteria. It is a prospective, randomized, controlled, multicentric, open-label clinical trial.
The goal is to recruit 100 patients.
Detailed description
Acute Respiratory Distress Syndrome (ARDS) is the most severe form of COVID-19 with a mortality reaching 50%. To date, no specific therapy has been shown to be effective. During an acute viral respiratory infection, lungs are the site of an intense neutrophil recruitment. Recruited neutrophils generate NETs (extracellular neutrophil traps) in the alveoli and bronchioles. NETs have been shown to be involved in bronchoalveolar congestion and amplification of the inflammatory response during viral pneumonia responsible for ARDS. Deoxyribonuclease 1 (DNAse 1) is an enzyme capable of cutting apart extracellular DNA strands, the backbone of NETs. The administration of recombinant human DNAse 1 (dornase alfa) leads to the loosening of the broncho-alveolar mucus and to a reduction in the inflammatory response within the alveoli.
By conducting a randomized, open-label, multicenter, controlled trial, our goal is to evaluate the efficacy and safety of aerosolized intra-tracheal dornase alfa administration in mechanically ventilated patients hospitalized for COVID19-related ARDS.
This is a randomized, controlled, multicentric, open-label clinical trial to evaluate the efficacy and safety of dornase alfa administration aerosol, intensive care hospitalized patients with COVID19-related ARDS.
The comparison of D7-D0 between the groups will be carried out using a linear regression fitted to the stratification factors.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Dornase alfa will be administered by nebulization, at a dose of 2500 IU twice daily, 12 hours apart, for 7 consecutive days, using a vibrating mesh nebulizer. The remainder of the management will be performed in accordance with good practice, including mechanical ventilation (protective ventilation, PEEP > 5 cmH2O, tracheal balloon pressure checking every 4 hours or automatic device, 30° head of the bed elevation, tidal volume 6-8mL/kg, plateau pressure < 30cmH2O), neuromuscular blockers if necessary, prone position if PaO2/FiO2<150, early enteral nutrition, glycemic control, a sedation protocol based on the RASS score.tracheal balloon pressure checking every 4 hours or automatic device, 30° head of the bed elevation, tidal volume 6-8mL/kg, plateau pressure < 30cmH2O), neuromuscular blockers if necessary, prone position if PaO2/FiO2<150, early enteral nutrition, glycemic control, a sedation protocol based on the RASS score.
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Drug: Dornase Alfa Inhalation Solution [Pulmozyme]Dornase alfa will be administered by nebulization, at a dose of 2500 IU twice daily, 12 hours apart, for 7 consecutive days, using a vibrating mesh nebulizer. The remainder of the management will be performed in accordance with good practice, including mechanical ventilation (protective ventilation, PEEP > 5 cmH2O, tracheal balloon pressure checking every 4 hours or automatic device, 30° head of the bed elevation, tidal volume 6-8mL/kg, plateau pressure < 30cmH2O), neuromuscular blockers if necessary, prone position if PaO2/FiO2<150, early enteral nutrition, glycemic control, a sedation protocol based on the RASS score. |
| Control group | Active comparator | Procedure: standard procedurePatients will receive the usual care in accordance with good practice. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adult patient (age ≥ 18 years old);
- Hospitalized in intensive care ;
- Severe COVID-19 pneumonia (positive diagnosis by RT-PCR or SARS-CoV-2 antigen test on nasopharyngeal or deep respiratory specimen and/or evocative thoracic scan: frosted glass opacities, consolidation, cross-linking, thickening of interlobular septa, peripheral nodules) with ARDS criteria according to Berlin criteria (PaO2/FiO2 ≤ 300 and PEP ≥ 5).
- With respiratory assistance (intubated or NIV or ONHD) for less than 8 days;
- With an expected duration of respiratory assistance > 48 hours;
Key exclusion criteria (3 listed)
- Known hypersensitivity to Dornase alfa or any of the excipients;
- Pregnant or breastfeeding status;
- Patient with legal protection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dornase Alfa Inhalation Solution [Pulmozyme]Administered by nebulization, at a dose of 2500 IU twice daily, 12 hours apart, for 7 consecutive days | Drug | Experimental group |
| standard procedurePatients will receive the usual care in accordance with good practice. | Procedure or surgery | Control group |
Primary outcome
Efficacy of intratracheal administration: occurrence of at least one grade improvement
Time frame: Day 7
The primary endpoint is the occurrence of at least one grade improvement between D0 (inclusion) and D7 in the ARDS scale severity (Berlin criteria). For instance from severe to moderate or from moderate to mild
Results and safety
The study was stopped early (reason given: No signal of benefit of treatment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2022.
- Derived from this study: PubMed 41125713Gregoire C, Di Meglio L, Le Cossec C, Ho-Tin-Noe B, Nomenjanahary MS, Guillaume J, Hamdani M, Losser MR, Lambiotte F, Le Tacon S, Cantier M, Engrand N, Yavchitz A, Trouiller P, Desilles JP, Pottecher J. Multicenter randomized trial assessing efficacy and safety of aerosolized dornase Alfa in COVID-19 ARDS. Sci Rep. 2025 Oct 22;15(1):36876. doi: 10.1038/s41598-025-20832-x.
- Derived from this study: PubMed 32560746Desilles JP, Gregoire C, Le Cossec C, Lambert J, Mophawe O, Losser MR, Lambiotte F, Le Tacon S, Cantier M, Engrand N, Trouiller P, Pottecher J. Efficacy and safety of aerosolized intra-tracheal dornase alfa administration in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS): a structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 19;21(1):548. doi: 10.1186/s13063-020-04488-8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles Grégoire, MD principal investigator
Hôpital Fondation A de Rothschild
Julien Pottecher, MD study chair
CHRU Strasbourg
Fabien Lambiotte, MD study chair
CH VALENCIENNES
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dornase Alfa Inhalation Solution [Pulmozyme] and standard procedure in people with COVID-19 and Acute Respiratory Distress Syndrome, run by Fondation Ophtalmologique Adolphe de Rothschild at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: No signal of benefit of treatment.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of intratracheal administration: occurrence of at least one grade improvement (time frame: Day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04355364, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2022.