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.
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.
Drug: Dornase Alfa Inhalation Solution [Pulmozyme]
Administered by nebulization, at a dose of 2500 IU twice daily, 12 hours apart, for 7 consecutive days
Procedure: standard procedure
Patients will receive the usual care in accordance with good practice.
inclusion criteria
- 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;
Exclusion Criteria:
- Known hypersensitivity to Dornase alfa or any of the excipients;
- Pregnant or breastfeeding status;
- Patient with legal protection.
Hôpital Fondation A. de Rotschhild
Paris, France