Dornase Alfa for ARDS in Patients With Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)
Condition: SARS-CoV 2; ARDS
Intervention: Dornase Alfa Inhalation Solution
Intervention description: Nebulized dornase alfa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Nebulized dornase alfa will be administered through the ventilator circuit at a dose of 2.5 mg, 12 hours apart, for 3 consecutive days. Patients will also receive lung protective ventilation (VC 6-8 ml/kg predicted body weight), plateau pressure < 30 centimeters of water pressure (cmH2O), targeted driving pressure < 15, neuromuscular blockade if indicated, and prone positioning based upon arterial blood content to fraction of inspired oxygen ratio (PaO2/FiO2) < 150 or upon treating physician decision; along with all other ICU care based upon best practice standards and evidence based medicine.
Masking: Single (Participant)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study is designed to evaluate a potential mechanism by which a hyperactive immune
      response may contribute to death from SARS-CoV-2; by an excessive neutrophil-mediated
      deposition of cell-free DNA in neutrophil extracellular traps (NET). Excessive amounts of
      NETs can increase rigidity of mucus, clog airways, and be agents for the development of acute
      respiratory distress (Narasaraju et al., Am J Pathol. 2011). Many aspects of this pathway
      have been observed in severe SARS-CoV-2 (Zhang et al., Respiratory research. 2020). Dornase
      alfa (DNAse I; Pulmozyme (Genentech) is a nebulized drug that works by degrading cell-free
      DNA and thus promoting airway clearance and recovery. The investigators hypothesize that by
      thinning mucus and degrading these NETs further lung damage may be prevented and a reduction
      in time to recovery may occur. The two aims of the study are to see if inhaled/nebulized
      dornase alfa will improve clinical outcome measures in SARS-CoV-2 related acute respiratory
      distress syndrome (ARDS) and to see if dornase alfa reduces the amount of bronchoalveolar
      lavage and blood markers of NET activity.

      The study will recruit patients who are on mechanical ventilation for respiratory failure
      related to SARS-CoV-2 positive infection and have ARDS based upon Berlin criteria.

      The investigators aim to recruit 10-20 patients for this study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age > 18 years

          -  Hospitalized and mechanically ventilated for illness related to SARS-CoV-2

          -  Confirmed positive SARS-CoV-2 infection by Polymerase chain reaction (PCR)

          -  individual or surrogate ability to sign informed consent

          -  negative, urine-based pregnancy test in females

        Exclusion Criteria:

          -  contraindication or intolerance to dornase alfa

          -  mechanical ventilation expected to be less than 48 hours

          -  life expectancy less than 24 hours based upon judgement of treating physician

          -  pregnant

          -  inability to obtain informed consent