Aerosoliserat DNase for Treatment of Respiratory Failure in Severe COVID-19

Study Overview
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Brief Summary
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Recent observations have suggested a role of neutrophil extracellular traps (NETs) in the pathophysiology of severe COVID-19. The aim of the study is to assess efficacy and safety of aerosolized DNase I to remove NETs and decrease respiratory distress in patients with COVID-19.

Detailed Description
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Study objectives: Primary objective: To compare the treatment effect of aerosolized DNase I to that of placebo (NaCl, 0.9%) on time to cessation of oxygen therapy or discharge from hospital in hospitalized patients with COVID-19 and respiratory dysfunction. Secondary objectives: To compare the treatment effect of aerosolized DNase I to that of placebo (NaCl, 0.9%) on 28-day mortality, days alive and without ventilator treatment, days alive and without high flow nasal oxygen treatment (Optiflow), length of stay in the ICU, days alive and outside hospital, relapse of hypoxia, days alive and without need for supplemental oxygen, adverse reactions. Exploratory objectives: To compare the treatment effect of aerosolized DNase I to that of placebo (NaCl, 9%) on quantification of NETs in respiratory secretions and on the incidence of clinical thromboembolic events. Study design: Phase 2 open-label randomized controlled multicentre trial. The study period is 28 days from randomization. A long term follow-up on mortality and readmission will also be collected via patient medical records/registries at day 90, day 180, and day 360 after randomization.

Official Title
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Aerosoliserat DNase for Treatment of Respiratory Failure in Severe COVID-19 - a Phase 2, Single-blinded, Randomized Study

Conditions
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COVID-19

Intervention / Treatment
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* Drug: aerosolized DNase
* Drug: NaCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old Admitted to hospital ward or ICU A positive PCR test for SARS-CoV-2 from throat swab or nasopharynx An oxygen saturation ≤90% after maximum 15 minutes without supplemental oxygen Signed informed consent Exclusion Criteria: Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation Known or suspected allergy against Pulmozyme Chronic obstructive pulmonary disease stage III-IV or another comparable chronic respiratory disease Participation in a clinical study with an investigational product during the last 30 days Previous participation in this study Pregnancy. Women of childbearing potential must agree to use contraceptives for the duration of the study period Any condition that, in the opinion of the Investigator, would place the patient at increased risk or preclude the patient's compliance with the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aerosolized DNase I<br> | Drug: aerosolized DNase<br>* DNase<br>|
| Placebo Comparator: NaCl<br> | Drug: NaCl<br>* NaCl 0.9%, isotonic saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to cessation of oxygen therapy DNase I to that of placebo (NaCl, 0.9%) on time to cessation of oxygen therapy hospitalized patients with COVID-19 and respiratory dysfunction. | Number of Days to cessation of oxygen therapy after start of treatment | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day mortality | Number of diseased patients up to 28 Days after start of treatment | 28 days | 
| Number of Days alive and without ventilator treatment | Number of Days alive and without ventilator treatment up to 28 Days after start of treatment | 28 days | 
| Number of Days alive and without high flow nasal oxygen treatment (Optiflow) | Number of Days alive and without high flow nasal oxygen treatment (Optiflow) up to 28 Days after start of treatment | 28 days | 
| Number of Days alive and free of stay in the ICU | Number of Days alive and free of stay in the ICU up to 28 Days after start of treatment | 28 days | 
| Number of Days alive and outside hospital | Number of Days alive and outside hospital up to 28 Days after start of treatment | 28 days | 
| Number of Days alive and free of a new episode and with oxygen saturation ≤93% after primary endpoint has been met | Number of Days alive and free of a new episode and with oxygen saturation ≤93% after primary endpoint has been met up to 28 Days after start of treatment | 28 days | 
| Number of Days alive and without need of supplemental oxygen | Number of Days alive and without need of supplemental oxygen up to 28 Days after start of treatment | 28 days | 
| Number of patients with adverse reactions | Number of patients with adverse reactions reported up to 28 Days after start of treatment | 28 days |