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COVID-19 InfectionPhase 1DISCONNECT-1NCT04409925

DISmantling COvid iNduced Neutrophil ExtraCellular Traps (DISCONNECT-1)

A Phase 1 study testing rhDNase I in people with COVID-19 Infection, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 2 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
COVID-19 Infection
What is being tested?
rhDNase I
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
2 sitesCanada
Study dates
25 Dec 2020to 1 Aug 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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):
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  • 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.

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

2 sites in 1 country.

Canada2 sites

  • Hamilton General Hospital, Hamilton Health Sciences

    Hamilton, Ontario, L8L 2X2

  • McGill University Health Centre

    Montreal, Quebec, H4A 3J1

Other trials in Canada

About this study

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

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.

Read the 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.
Being tested
rhDNase I
Keywords
Neutrophil Extracellular Traps, NETs, Neutrophils, rhDNase1
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rhDNase IDrug

    Also called Pulmozyme

    Inhaled nebulisations

Study groups in NCT04409925
Study groupRoleWhat they receive
rhDNase1 (Pulmozyme, Roche/Genentech)ExperimentalSingle Arm: rhDNase1 (Pulmozyme, Roche/Genentech) 2.5 mg inhaled nebulisations BID, for a maximum of 14 consecutive days.
Receives: Drug: rhDNase I

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 9 months

Secondary outcomes (16)

  1. Time to first study participant enrolment

    Time elapsed between the study opening date and the first patient enrolment date.

    Measured: Up to 2 weeks

  2. Enrolment rate

    Number of patients enrolled per week following the start of the study.

    Measured: Up to 9 months

  3. 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).

    Measured: Up to 9 months

  4. Completeness of drug delivery

    Percentage of doses missed compared to completed, including reasons for missed doses, per patient.

    Measured: Up to 9 months

  5. Completeness of study-specific tests or procedures

    Percentage of tests or procedures missed compared to completed, per patient.

    Measured: Up to 9 months

  6. Completeness of data collection

    Percentage of missed data compared to completed data, per patient.

    Measured: Up to 9 months

  7. Hypoxia rate

    Extent of hypoxia rate is defined as the number of patients requiring supplemental oxygen, categorized by type of oxygen requirement.

    Measured: Up to 9 months

  8. Supplemental oxygen requirement type

    Type of oxygen in FiO2 requirements needed by each patient in the study, if applicable.

    Measured: Up to 9 months

  9. Progression to mechanical ventilation rate

    Number of patients progressing to requiring intubation and mechanical ventilation.

    Measured: Up to 9 months

  10. Duration of mechanical ventilation

    Duration in days, for patients requiring intubation and mechanical ventilation, if applicable.

    Measured: Up to 9 months

  11. 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.

    Measured: Up to 9 months

  12. Renal dysfunction rate

    Number of patients with renal dysfunction, classified by stage (1, 2 or 3).

    Measured: Up to 9 months

  13. Renal dysfunction extent

    Extent of change in creatinine from baseline.

    Measured: Up to 9 months

  14. Secondary bacterial infections rate

    Number of patients contracting secondary bacterial infections (pneumonia, bacteremia and other).

    Measured: Up to 9 months

  15. Duration of ICU admission

    In days, length of stay in the ICU.

    Measured: Up to 9 months

  16. 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).

    Measured: Up to 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jun 2020
  2. Study start25 Dec 2020
  3. Primary completion1 Apr 2021
  4. Study completion1 Aug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04409925
Sponsor's protocol ID
DISCONNECT-1
Acronym
DISCONNECT-1
Status last verified
Mar 2023
First submitted
13 May 2020
Last updated
17 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing rhDNase I in people with COVID-19 Infection, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 2 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of inhaled rhDNase1 in non-ventilated COVID-19 patients by reporting of adverse events (time frame: 9 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04409925.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2023.

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