Clinical trial NCT04541979: Aerosoliserat DNase for Treatment of Respiratory Failure in Severe COVID-19
Official title: Aerosoliserat DNase for Treatment of Respiratory Failure in Severe COVID-19 - a Phase 2, Single-blinded, Randomized Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Lead sponsor: Region Skane
Sponsor class: OTHER
First posted: 2020-09-09
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 28 days
Secondary outcomes:
measure: 28-day mortality
timeFrame: 28 days
measure: Number of Days alive and without ventilator treatment
timeFrame: 28 days
measure: Number of Days alive and without high flow nasal oxygen treatment (Optiflow)
timeFrame: 28 days
measure: Number of Days alive and free of stay in the ICU
timeFrame: 28 days
measure: Number of Days alive and outside hospital
timeFrame: 28 days
measure: Number of Days alive and free of a new episode and with oxygen saturation ≤93% after primary endpoint has been met
timeFrame: 28 days
measure: Number of Days alive and without need of supplemental oxygen
timeFrame: 28 days
measure: Number of patients with adverse reactions
timeFrame: 28 days
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Lund ED
Study officials:
affiliation: Region Skåne
name: Adam Linder, MD
role: PRINCIPAL_INVESTIGATOR
References: