Back to resultsDISmantling COvid iNduced Neutrophil ExtraCellular Traps (DISCONNECT-1) (DISCONNECT-1)
Primary Purpose
COVID-19 Infection
Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
rhDNase I
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 Infection focused on measuring Neutrophil Extracellular Traps, NETs, Neutrophils, rhDNase1
Eligibility Criteria
Inclusion criteria
- Verbal informed consent by patient (or legal representative), done in the presence of an impartial witness. The consent is signed by the Principal Investigator (or Co-Investigator) and the impartial witness.
- Participants who are at least 18 years of age on the day of consenting to the informed consent
- COVID-19 (SARS-CoV2) positive test by nasopharyngeal swab
- Admitted to the ICU in negative pressure rooms
Mild to severe respiratory illness (defined as requiring admission* and/or supplemental oxygen), not intubated or on mechanical ventilation at screening and enrolment.
Admission respiratory criteria (1 of the following):
- Dyspnea at rest or during minimal activity (sitting, talking, coughing, swallowing);
- Respiratory rate > 22/minute;
- PaO2 < 65mmHg or oxygen saturation < 90% or PaO2/FiO2 ratio of less than 300
- Infiltrate on CXR (or worsening CXR, if baseline CXR at admission was already abnormal)
Mild disease with hospitalization:
- No oxygen therapy;
- Oxygen by mask or nasal prongs.
Severe disease with hospitalization (requiring greater than 40% oxygen):
- Oxygen by non-invasive ventilation or high flow oxygen/Optiflow.
Exclusion criteria:
- Patients requiring mechanical ventilation at screening
- Previous or current treatment with rhDNase1
- Ongoing experimental treatment with other inhaled therapies through COVID-19-related clinical trials
- Known hypersensitivity to NET inhibitor or recombinant protein products
- Known hypersensitivity to Chinese Hamster Ovary cell products or any component of the product
- Known history of immunodeficiency, HBV, HCV, HIV (Note: No HBV, HCV or HIV testing is required unless mandated by local health authority)
- Known history of immunosuppressive disorders, such as primary/secondary immunodeficiencies, lymphoproliferative diseases
- Active pregnancy at any stage or lactation
- Patients deemed incapable and/or incompetent
Sites / Locations
- Hamilton General Hospital, Hamilton Health Sciences
- McGill University Health Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
rhDNase1 (Pulmozyme, Roche/Genentech)
Arm Description
Single Arm: rhDNase1 (Pulmozyme, Roche/Genentech) 2.5 mg inhaled nebulisations BID, for a maximum of 14 consecutive days.
Outcomes
Primary Outcome Measures
Safety of inhaled rhDNase1 in non-ventilated COVID-19 patients by reporting of adverse events
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 Outcome Measures
Time to first study participant enrolment
Time elapsed between the study opening date and the first patient enrolment date.
Enrolment rate
Number of patients enrolled per week following the start of the study.
Eligible patient consent rate
Number of patients meeting eligibility through inclusion and exclusion criteria that are consented and enrolled into the study, as compared to the total number of patients meeting criteria (enrolled and non-enrolled).
Completeness of drug delivery
Percentage of doses missed compared to completed, including reasons for missed doses, per patient.
Completeness of study-specific tests or procedures
Percentage of tests or procedures missed compared to completed, per patient.
Completeness of data collection
Percentage of missed data compared to completed data, per patient.
Hypoxia rate
Extent of hypoxia rate is defined as the number of patients requiring supplemental oxygen, categorized by type of oxygen requirement.
Supplemental oxygen requirement type
Type of oxygen in FiO2 requirements needed by each patient in the study, if applicable.
Progression to mechanical ventilation rate
Number of patients progressing to requiring intubation and mechanical ventilation.
Duration of mechanical ventilation
Duration in days, for patients requiring intubation and mechanical ventilation, if applicable.
Radiological progression
Number of patients who show progression on imaging suggestive of ARDS such as bilateral lung involvement, as reviewed by study's thoracic radiologist.
Renal dysfunction rate
Number of patients with renal dysfunction, classified by stage (1, 2 or 3).
Renal dysfunction extent
Extent of change in creatinine from baseline.
Secondary bacterial infections rate
Number of patients contracting secondary bacterial infections (pneumonia, bacteremia and other).
Duration of ICU admission
In days, length of stay in the ICU.
Time to hospital discharge or in-hospital mortality
Time elapsed between enrolment into the study (at admission), and endpoint (discharge from ICU or in-hospital mortality).
Full Information
NCT ID
NCT04409925
First Posted
May 13, 2020
Last Updated
March 16, 2023
Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
Collaborators
Hamilton Health Sciences Corporation, Hoffmann-La Roche, Exactis Innovation
1. Study Identification
Unique Protocol Identification Number
NCT04409925
Brief Title
DISmantling COvid iNduced Neutrophil ExtraCellular Traps (DISCONNECT-1)
Acronym
DISCONNECT-1
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
December 25, 2020 (Actual)
Primary Completion Date
April 1, 2021 (Actual)
Study Completion Date
August 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
Collaborators
Hamilton Health Sciences Corporation, Hoffmann-La Roche, Exactis Innovation
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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:
to evaluate the safety and feasibility of inhaled rhDNase1 in severely ill COVID-19 patients requiring admission;
to evaluate the impact of rhDNase1 in limiting progression of disease and COVID-19 related complications in these patients;
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 Infection
Keywords
Neutrophil Extracellular Traps, NETs, Neutrophils, rhDNase1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
rhDNase1 (Pulmozyme, Roche/Genentech)
Arm Type
Experimental
Arm Description
Single Arm: rhDNase1 (Pulmozyme, Roche/Genentech) 2.5 mg inhaled nebulisations BID, for a maximum of 14 consecutive days.
Intervention Type
Drug
Intervention Name(s)
rhDNase I
Other Intervention Name(s)
Pulmozyme
Intervention Description
Inhaled nebulisations
Primary Outcome Measure Information:
Title
Safety of inhaled rhDNase1 in non-ventilated COVID-19 patients by reporting of adverse events
Description
Rate of all adverse events, rate of serious adverse events, rate of grade 3/4/5 adverse events, rate of drug-related adverse events.
Time Frame
9 months
Secondary Outcome Measure Information:
Title
Time to first study participant enrolment
Description
Time elapsed between the study opening date and the first patient enrolment date.
Time Frame
Up to 2 weeks
Title
Enrolment rate
Description
Number of patients enrolled per week following the start of the study.
Time Frame
Up to 9 months
Title
Eligible patient consent rate
Description
Number of patients meeting eligibility through inclusion and exclusion criteria that are consented and enrolled into the study, as compared to the total number of patients meeting criteria (enrolled and non-enrolled).
Time Frame
Up to 9 months
Title
Completeness of drug delivery
Description
Percentage of doses missed compared to completed, including reasons for missed doses, per patient.
Time Frame
Up to 9 months
Title
Completeness of study-specific tests or procedures
Description
Percentage of tests or procedures missed compared to completed, per patient.
Time Frame
Up to 9 months
Title
Completeness of data collection
Description
Percentage of missed data compared to completed data, per patient.
Time Frame
Up to 9 months
Title
Hypoxia rate
Description
Extent of hypoxia rate is defined as the number of patients requiring supplemental oxygen, categorized by type of oxygen requirement.
Time Frame
Up to 9 months
Title
Supplemental oxygen requirement type
Description
Type of oxygen in FiO2 requirements needed by each patient in the study, if applicable.
Time Frame
Up to 9 months
Title
Progression to mechanical ventilation rate
Description
Number of patients progressing to requiring intubation and mechanical ventilation.
Time Frame
Up to 9 months
Title
Duration of mechanical ventilation
Description
Duration in days, for patients requiring intubation and mechanical ventilation, if applicable.
Time Frame
Up to 9 months
Title
Radiological progression
Description
Number of patients who show progression on imaging suggestive of ARDS such as bilateral lung involvement, as reviewed by study's thoracic radiologist.
Time Frame
Up to 9 months
Title
Renal dysfunction rate
Description
Number of patients with renal dysfunction, classified by stage (1, 2 or 3).
Time Frame
Up to 9 months
Title
Renal dysfunction extent
Description
Extent of change in creatinine from baseline.
Time Frame
Up to 9 months
Title
Secondary bacterial infections rate
Description
Number of patients contracting secondary bacterial infections (pneumonia, bacteremia and other).
Time Frame
Up to 9 months
Title
Duration of ICU admission
Description
In days, length of stay in the ICU.
Time Frame
Up to 9 months
Title
Time to hospital discharge or in-hospital mortality
Description
Time elapsed between enrolment into the study (at admission), and endpoint (discharge from ICU or in-hospital mortality).
Time Frame
Up to 9 months
Other Pre-specified Outcome Measures:
Title
Exploratory: NET quantification in blood, correlated to COVID-19 disease severity and complications.
Time Frame
Up to 9 months
Title
Exploratory: Blood clotting and fibrinolysis assays, correlated to COVID-19 disease severity and complications.
Time Frame
Up to 9 months
Title
Exploratory: Cytokine profile alterations in blood, correlated to COVID-19 disease severity and complications
Time Frame
Up to 9 months
Title
Exploratory: Neutrophil RNA sequencing in blood, correlated to COVID-19 disease severity and complications
Time Frame
Up to 9 months
Title
Length of PCR positivity
Description
Defined as number of days between first positive PCR test and last positive PCR test, usually done by nasopharyngeal swabs. Tests will be performed as mandated by standard of care only.
Time Frame
Up to 9 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria
Verbal informed consent by patient (or legal representative), done in the presence of an impartial witness. The consent is signed by the Principal Investigator (or Co-Investigator) and the impartial witness.
Participants who are at least 18 years of age on the day of consenting to the informed consent
COVID-19 (SARS-CoV2) positive test by nasopharyngeal swab
Admitted to the ICU in negative pressure rooms
Mild to severe respiratory illness (defined as requiring admission* and/or supplemental oxygen), not intubated or on mechanical ventilation at screening and enrolment.
Admission respiratory criteria (1 of the following):
Dyspnea at rest or during minimal activity (sitting, talking, coughing, swallowing);
Respiratory rate > 22/minute;
PaO2 < 65mmHg or oxygen saturation < 90% or PaO2/FiO2 ratio of less than 300
Infiltrate on CXR (or worsening CXR, if baseline CXR at admission was already abnormal)
Mild disease with hospitalization:
No oxygen therapy;
Oxygen by mask or nasal prongs.
Severe disease with hospitalization (requiring greater than 40% oxygen):
Oxygen by non-invasive ventilation or high flow oxygen/Optiflow.
Exclusion criteria:
Patients requiring mechanical ventilation at screening
Previous or current treatment with rhDNase1
Ongoing experimental treatment with other inhaled therapies through COVID-19-related clinical trials
Known hypersensitivity to NET inhibitor or recombinant protein products
Known hypersensitivity to Chinese Hamster Ovary cell products or any component of the product
Known history of immunodeficiency, HBV, HCV, HIV (Note: No HBV, HCV or HIV testing is required unless mandated by local health authority)
Known history of immunosuppressive disorders, such as primary/secondary immunodeficiencies, lymphoproliferative diseases
Active pregnancy at any stage or lactation
Patients deemed incapable and/or incompetent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan Spicer, MD, PhD
Organizational Affiliation
McGill University Health Centre/Research Institute of the McGill University Health Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hamilton General Hospital, Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L 2X2
Country
Canada
Facility Name
McGill University Health Centre
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
DISmantling COvid iNduced Neutrophil ExtraCellular Traps (DISCONNECT-1)
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