Phase I Pilot Study Investigating the Safety and Feasibility of Inhaled rhDNase1 and Its Impact on Neutrophil Extracellular Traps (NETs) in Non-Ventilated COVID-19 Infected Patients
Overview
- Phase
- Phase 1
- Intervention
- rhDNase I
- Conditions
- COVID-19 Infection
- Sponsor
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Enrollment
- 15
- Locations
- 2
- Primary Endpoint
- Safety of inhaled rhDNase1 in non-ventilated COVID-19 patients by reporting of adverse events
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a pilot study to investigate the safety and feasibility of rhDNase1 and its impact on neutrophil extracellular traps (NETs) in COVID-19 infected patients.
Detailed Description
It has been reported that elevated numbers of neutrophils (PMNs) in the blood predicts poor outcomes and severity in patients with COVID-19 infections. Acute inflammation results in formation of neutrophil extracellular traps (NETs) by PMNs and NK cells. Pre-clinical studies showed that NETs are critically involved in the pathophysiology of ARDS and increased capacity of PMNs to form NETs was shown to correlated with increased severity and mortality in patients with ARDS after community-acquired pneumonia. In early reports, patients with severe COVID-19 infections were also found to have radiological and clinical findings of Acute Respiratory Distress Syndrome (ARDS). NETs can be degraded by DNase1 for which there is a human recombinant equivalent rhDNase1. This study proposes: 1. to evaluate the safety and feasibility of inhaled rhDNase1 in severely ill COVID-19 patients requiring admission; 2. to evaluate the impact of rhDNase1 in limiting progression of disease and COVID-19 related complications in these patients; 3. and to investigate NETs as possible therapeutic targets in severe COVID-19 patients by quantifying levels of circulating NETs in the blood and sputum and correlating these with oxygen requirements, need for mechanical ventilation, duration of mechanical ventilation, radiological progression of ARDS, secondary bacterial infections (pneumonia, bacteremia and other), renal dysfunction, duration of ICU admission, and time to discharge or mortality.
Investigators
Jonathan Spicer
Principal Investigator
McGill University Health Centre/Research Institute of the McGill University Health Centre
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
rhDNase1 (Pulmozyme, Roche/Genentech)
Single Arm: rhDNase1 (Pulmozyme, Roche/Genentech) 2.5 mg inhaled nebulisations BID, for a maximum of 14 consecutive days.
Intervention: rhDNase I
Outcomes
Primary Outcomes
Safety of inhaled rhDNase1 in non-ventilated COVID-19 patients by reporting of adverse events
Time Frame: 9 months
Rate of all adverse events, rate of serious adverse events, rate of grade 3/4/5 adverse events, rate of drug-related adverse events.
Secondary Outcomes
- Completeness of drug delivery(Up to 9 months)
- Secondary bacterial infections rate(Up to 9 months)
- Eligible patient consent rate(Up to 9 months)
- Completeness of study-specific tests or procedures(Up to 9 months)
- Hypoxia rate(Up to 9 months)
- Radiological progression(Up to 9 months)
- Duration of ICU admission(Up to 9 months)
- Progression to mechanical ventilation rate(Up to 9 months)
- Time to hospital discharge or in-hospital mortality(Up to 9 months)
- Enrolment rate(Up to 9 months)
- Duration of mechanical ventilation(Up to 9 months)
- Time to first study participant enrolment(Up to 2 weeks)
- Completeness of data collection(Up to 9 months)
- Supplemental oxygen requirement type(Up to 9 months)
- Renal dysfunction rate(Up to 9 months)
- Renal dysfunction extent(Up to 9 months)