DISmantling COvid iNduced Neutrophil ExtraCellular Traps (DISCONNECT-1)

Phase 1

Completed

• Conditions: COVID-19 Infection
• Interventions: Drug: rhDNase I

• Registration Number: NCT04409925
• Lead Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

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.

Study Timeline

• Study First Submitted: 2020-05-13
• Study First Submitted QC: 2020-05-28
• Study First Posted: 2020-06-01
• Study Start: 2020-12-25
• Primary Completion: 2021-04-01
• Study Completion: 2021-08-01
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-16
• Last Update Posted: 2023-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
rhDNase1 (Pulmozyme, Roche/Genentech)	rhDNase I	Single Arm: rhDNase1 (Pulmozyme, Roche/Genentech) 2.5 mg inhaled nebulisations BID, for a maximum of 14 consecutive days.

Primary Outcome Measures

Name	Time	Method
Safety of inhaled rhDNase1 in non-ventilated COVID-19 patients by reporting of adverse events	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 Outcome Measures

Name	Time	Method
Completeness of drug delivery	Up to 9 months	Percentage of doses missed compared to completed, including reasons for missed doses, per patient.
Secondary bacterial infections rate	Up to 9 months	Number of patients contracting secondary bacterial infections (pneumonia, bacteremia and other).
Eligible patient consent rate	Up to 9 months	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 study-specific tests or procedures	Up to 9 months	Percentage of tests or procedures missed compared to completed, per patient.
Hypoxia rate	Up to 9 months	Extent of hypoxia rate is defined as the number of patients requiring supplemental oxygen, categorized by type of oxygen requirement.
Radiological progression	Up to 9 months	Number of patients who show progression on imaging suggestive of ARDS such as bilateral lung involvement, as reviewed by study's thoracic radiologist.
Duration of ICU admission	Up to 9 months	In days, length of stay in the ICU.
Progression to mechanical ventilation rate	Up to 9 months	Number of patients progressing to requiring intubation and mechanical ventilation.
Time to hospital discharge or in-hospital mortality	Up to 9 months	Time elapsed between enrolment into the study (at admission), and endpoint (discharge from ICU or in-hospital mortality).
Enrolment rate	Up to 9 months	Number of patients enrolled per week following the start of the study.
Duration of mechanical ventilation	Up to 9 months	Duration in days, for patients requiring intubation and mechanical ventilation, if applicable.
Time to first study participant enrolment	Up to 2 weeks	Time elapsed between the study opening date and the first patient enrolment date.
Completeness of data collection	Up to 9 months	Percentage of missed data compared to completed data, per patient.
Supplemental oxygen requirement type	Up to 9 months	Type of oxygen in FiO2 requirements needed by each patient in the study, if applicable.
Renal dysfunction rate	Up to 9 months	Number of patients with renal dysfunction, classified by stage (1, 2 or 3).
Renal dysfunction extent	Up to 9 months	Extent of change in creatinine from baseline.

Trial Locations

Locations (2)

McGill University Health Centre; 🇨🇦 Montreal, Quebec, Canada

Hamilton General Hospital, Hamilton Health Sciences; 🇨🇦 Hamilton, Ontario, Canada