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

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

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.

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: aerosolized DNase; Drug: NaCl

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Adam Linder, MD; Phone Number: 004646171130; Email: adam.linder@med.lu.se

Study Locations

• Sweden
  • Lund, Sweden
    • Recruiting
    • Lund ED
    • Contact: Adam Linder; Email: adam.linder@med.lu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aerosolized DNase I	Drug: aerosolized DNase; DNase
Placebo Comparator: NaCl	Drug: NaCl; NaCl 0.9%, isotonic saline

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Region Skane
• Investigators: Principal Investigator: Adam Linder, MD, Region Skane

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: June 5, 2020
• First Submitted That Met QC Criteria: September 7, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: January 8, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Respiratory Insufficiency
• Other Study ID Numbers: NETSC-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: nn

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No