DISmantling COvid iNduced Neutrophil ExtraCellular Traps (DISCONNECT-1) (DISCONNECT-1)
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|ClinicalTrials.gov Identifier: NCT04409925|
Recruitment Status : Recruiting
First Posted : June 1, 2020
Last Update Posted : January 22, 2021
|Condition or disease||Intervention/treatment||Phase|
|COVID-19 Infection||Drug: rhDNase I||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||December 25, 2020|
|Estimated Primary Completion Date :||April 2021|
|Estimated Study Completion Date :||August 2021|
Experimental: rhDNase1 (Pulmozyme, Roche/Genentech)
Single Arm: rhDNase1 (Pulmozyme, Roche/Genentech) 2.5 mg inhaled nebulisations BID, for a maximum of 14 consecutive days.
Drug: rhDNase I
Other Name: Pulmozyme
- 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.
- Time to first study participant enrolment [ Time Frame: Up to 2 weeks ]Time elapsed between the study opening date and the first patient enrolment date.
- Enrolment rate [ Time Frame: Up to 9 months ]Number of patients enrolled per week following the start of the study.
- Eligible patient consent rate [ Time Frame: 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 drug delivery [ Time Frame: Up to 9 months ]Percentage of doses missed compared to completed, including reasons for missed doses, per patient.
- Completeness of study-specific tests or procedures [ Time Frame: Up to 9 months ]Percentage of tests or procedures missed compared to completed, per patient.
- Completeness of data collection [ Time Frame: Up to 9 months ]Percentage of missed data compared to completed data, per patient.
- Hypoxia rate [ Time Frame: Up to 9 months ]Extent of hypoxia rate is defined as the number of patients requiring supplemental oxygen, categorized by type of oxygen requirement.
- Supplemental oxygen requirement type [ Time Frame: Up to 9 months ]Type of oxygen in FiO2 requirements needed by each patient in the study, if applicable.
- Progression to mechanical ventilation rate [ Time Frame: Up to 9 months ]Number of patients progressing to requiring intubation and mechanical ventilation.
- Duration of mechanical ventilation [ Time Frame: Up to 9 months ]Duration in days, for patients requiring intubation and mechanical ventilation, if applicable.
- Radiological progression [ Time Frame: 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.
- Renal dysfunction rate [ Time Frame: Up to 9 months ]Number of patients with renal dysfunction, classified by stage (1, 2 or 3).
- Renal dysfunction extent [ Time Frame: Up to 9 months ]Extent of change in creatinine from baseline.
- Secondary bacterial infections rate [ Time Frame: Up to 9 months ]Number of patients contracting secondary bacterial infections (pneumonia, bacteremia and other).
- Duration of ICU admission [ Time Frame: Up to 9 months ]In days, length of stay in the ICU.
- Time to hospital discharge or in-hospital mortality [ Time Frame: Up to 9 months ]Time elapsed between enrolment into the study (at admission), and endpoint (discharge from ICU or in-hospital mortality).
- Exploratory: NET quantification in blood, correlated to COVID-19 disease severity and complications. [ Time Frame: Up to 9 months ]
- Exploratory: Blood clotting and fibrinolysis assays, correlated to COVID-19 disease severity and complications. [ Time Frame: Up to 9 months ]
- Exploratory: Cytokine profile alterations in blood, correlated to COVID-19 disease severity and complications [ Time Frame: Up to 9 months ]
- Exploratory: Neutrophil RNA sequencing in blood, correlated to COVID-19 disease severity and complications [ Time Frame: Up to 9 months ]
- Length of PCR positivity [ Time Frame: Up to 9 months ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04409925
|Contact: Aya Siblini, MSc||514-934-1934 ext firstname.lastname@example.org|
|Contact: Caroline Huynh, MD||514-934-1934 ext email@example.com|
|Hamilton General Hospital, Hamilton Health Sciences||Recruiting|
|Hamilton, Ontario, Canada, L8L 2X2|
|Contact: Alison Fox-Robichaud, MD MSc|
|McGill University Health Centre||Recruiting|
|Montreal, Quebec, Canada, H4A 3J1|
|Contact: Jonathan Spicer, MD PhD|
|Principal Investigator:||Jonathan Spicer, MD, PhD||McGill University Health Centre/Research Institute of the McGill University Health Centre|