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

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ClinicalTrials.gov Identifier: NCT04355364
Recruitment Status : Recruiting
First Posted : April 21, 2020
Last Update Posted : April 22, 2021
Sponsor:
Collaborators:
University Hospital, Strasbourg, France
Centre Hospitalier Régional Metz-Thionville
Information provided by (Responsible Party):
Fondation Ophtalmologique Adolphe de Rothschild

Study Description
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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.


Condition or disease Intervention/treatment Phase
COVID-19 Acute Respiratory Distress Syndrome Drug: Dornase Alfa Inhalation Solution [Pulmozyme] Procedure: standard procedure Phase 3

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
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Dornase Alfa Aerosol in ARDS Secondary to SARS-CoV-2 Coronavirus Respiratory Infection - COVID-19
Actual Study Start Date : April 21, 2020
Estimated Primary Completion Date : December 21, 2021
Estimated Study Completion Date : April 21, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Experimental group
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]
Administered by nebulization, at a dose of 2500 IU twice daily, 12 hours apart, for 7 consecutive days
Active Comparator: Control group
Patients will receive the usual care in accordance with good practice.
 Procedure: standard procedure
Patients will receive the usual care in accordance with good practice.


Outcome Measures
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Primary Outcome Measures :
  1. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04355364


Contacts
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Contact: Jean-Philippe Désilles 0148037068 jpdesilles@for.paris
Contact: Amélie Yavchitz 0148037068 ayavchitz@for.paris

Locations
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France
Hôpital Fondation A. de Rotschhild Recruiting
Paris, France
Contact: Amélie Yavchitz    0148036870      
Principal Investigator: Charles GREGOIRE         
Sponsors and Collaborators
Fondation Ophtalmologique Adolphe de Rothschild
University Hospital, Strasbourg, France
Centre Hospitalier Régional Metz-Thionville
Investigators
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Principal Investigator: Charles Grégoire Hôpital Fondation A de Rothschild
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Fondation Ophtalmologique Adolphe de Rothschild
ClinicalTrials.gov Identifier: NCT04355364    
Other Study ID Numbers: CGE_2020_9
First Posted: April 21, 2020    Key Record Dates
Last Update Posted: April 22, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Diseases
Respiratory Tract Diseases
 Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury