Efficacy and Safety of aerosolizedDornase Alfa Administration in Patients With COVID19 Induced ARDS (COVIDORNASE)

NCT04355364 | Terminated Phase 3

• 1 other identifier: CGE_2020_9
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

COVID-19; Acute Respiratory Distress Syndrome

Outcome Measures

Primary Outcomes (1)

• 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

  Day 7

Study Arms (2)

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.

Drug: Dornase Alfa Inhalation Solution [Pulmozyme]

Control group

ACTIVE COMPARATOR

Patients will receive the usual care in accordance with good practice.

Procedure: standard procedure

Interventions

Dornase Alfa Inhalation Solution [Pulmozyme] DRUG

Administered by nebulization, at a dose of 2500 IU twice daily, 12 hours apart, for 7 consecutive days

Experimental group

standard procedure PROCEDURE

Patients will receive the usual care in accordance with good practice.

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• Known hypersensitivity to Dornase alfa or any of the excipients;
• Pregnant or breastfeeding status;
• Patient with legal protection.

Sponsors & Collaborators

• Fondation Ophtalmologique Adolphe de Rothschild: lead
• University Hospital, Strasbourg, France: collaborator
• Centre Hospitalier Régional Metz-Thionville: collaborator

Study Sites (1)

Hôpital Fondation A. de Rotschhild

Paris, France

Location

Related Publications (2)

• 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.

  PMID: 41125713 DERIVED

• Desilles 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.

  PMID: 32560746 DERIVED

MeSH Terms

Conditions

COVID-19; Respiratory Distress Syndrome

Interventions

dornase alfa

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Charles Grégoire, MD

  Hôpital Fondation A de Rothschild

  PRINCIPAL INVESTIGATOR

• Julien Pottecher, MD

  CHRU Strasbourg

  STUDY CHAIR

• Fabien Lambiotte, MD

  CH VALENCIENNES

  STUDY CHAIR

• Serge Le Tacon, MD

  CHR Metz-Thionville

  STUDY CHAIR

• Marie-Reine Pr Losser

  CHRU Nancy

  STUDY CHAIR

• Pierre Kalfon, MD

  CH Chartres

  STUDY CHAIR

• Vincent Das, MD

  CH Montreuil

  STUDY CHAIR

• Karim Nourdine, MD

  Hôpital Drôme Nord

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 15, 2020
• First Posted: April 21, 2020
• Study Start: April 21, 2020
• Primary Completion: December 20, 2021
• Study Completion: December 20, 2021
• Last Updated: January 11, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)