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Trial record 1 of 1 for:    COVsurf
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A Clinical Trial of Nebulized Surfactant for the Treatment of Moderate to Severe COVID-19 (COVSurf)

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ClinicalTrials.gov Identifier: NCT04362059
Recruitment Status : Completed
First Posted : April 24, 2020
Last Update Posted : September 29, 2023
Sponsor:
Collaborators:
Bill and Melinda Gates Foundation
University College, London
Information provided by (Responsible Party):
University Hospital Southampton NHS Foundation Trust

Brief Summary:
Lung surfactant is present in the lungs. It covers the alveolar surface where it reduces the work of breathing and prevents the lungs from collapsing. In some respiratory diseases and in patients that require ventilation this substance does not function normally. This study will introduce surfactant to the patients lungs via the COVSurf Drug Delivery System

Condition or disease Intervention/treatment Phase
Respiratory Infections Device: COVSurf Drug Delivery System Other: Standard of Care Not Applicable

Detailed Description:

The hypothesis behind the proposed trial of surfactant therapy for COVID-19 infected patients requiring ventilator support is that endogenous surfactant is dysfunctional. This could be due to decreased concentration of surfactant phospholipid and protein, altered surfactant phospholipid composition, surfactant protein proteolysis and/or oedema protein inhibition of surfactant surface tension function and/or oxidative inactivation of surfactant proteins. Variations of these dysfunctional mechanisms have been reported in a range of lung diseases, including cystic fibrosis and severe asthma, and in child and adult patients with ARDS. Our studies of surfactant metabolism in adult ARDS patients showed altered percentage composition of surfactant PC, with decreased DPPC and increased surface tension-inactive unsaturated species, and decreased concentrations of both total PC and phosphatidylglycerol (PG)

The SARS-CoV-2 virus binds to the angiotensin converting enzyme-2 (ACE2) receptor, which is preferentially expressed in the peripheral lung ATII cells. Consequent viral infection of ATII cells could reduce cell number and impair the capacity of the lungs to synthesise and secrete surfactant. This, however, has not yet been demonstrated empirically in COVID-19 patients. If this is the case, then exogenous surfactant administration to the lungs is potential one treatment option to mitigate disease severity in these patients.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Clinical Trial of Nebulized Surfactant for the Treatment of Moderate to Severe COVID-19
Actual Study Start Date : June 18, 2020
Actual Primary Completion Date : November 30, 2022
Actual Study Completion Date : January 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment Arm
Patients will be administered surfactant via COVSurf Drug Delivery System
Device: COVSurf Drug Delivery System
Device introduces surfactant to the patients lungs

Active Comparator: Control Arm
Patients shall receive regular Standard of Care treatment
Other: Standard of Care
Standard of care treatment for respiratory illness




Primary Outcome Measures :
  1. Oxygenation Improvement [ Time Frame: 3 months ]
    To assess the improvement in oxygenation as determined by the PaO2/FiO2 ratio after treatment with study treatment

  2. Pulmonary ventilation Improvement [ Time Frame: 3 months ]
    To assess the improvement in pulmonary ventilation as determined by the Ventilation Index (VI), where VI = (Respiratory rate X PIP X PaCo2 (mmHg)/ 1000 after study treatment.

  3. IMV Need [ Time Frame: 3 months ]
    Need for invasive mechanical ventilation (IMV) (CPAP/NIV arm only)


Secondary Outcome Measures :
  1. Safety Assessment of Frequency and Severity of Adverse Events [ Time Frame: 3 months ]
    To assess safety as judged by the frequency and severity of adverse events and severe adverse events (SAEs).

  2. Change in PaO2/FiO2 ratio [ Time Frame: 3 months ]
    Mean change in PaO2/FiO2 ratio at 24 and 48 hours after study initiation.

  3. Mean Change in ventilatory index [ Time Frame: 48 hours ]
    Mean change in ventilatory index (VI) at 24 and 48 hours after study initiation

  4. Mean Change in pulmonary compliance [ Time Frame: 48 hours ]
    Mean change in pulmonary compliance (L/cmH2O) at 24 and 48 hours after study initiation in the IMV arm

  5. Mean Change in PEEP requirement [ Time Frame: 48 Hours ]
    Mean change in PEEP (Positive End-Expiratory Pressure) requirement at 24 and 48 hours after study initiation

  6. Clinical Improvement [ Time Frame: 28 days ]
    To evaluate clinical improvement defined by time to one improvement point on an ordinal scale, as described in the WHO master protocol (2020) daily while hospitalised and on days 15 and 28

  7. Mechanical ventilation duration [ Time Frame: 3 months ]
    Duration of mechanical ventilation

  8. Duration of days [ Time Frame: 3 months ]
    Duration of days of IMV or NIV or CPAP

  9. IMV free days [ Time Frame: 21 days ]
    Invasive Mechanical Ventilator (IMV) free days at day 21

  10. Ventilator support free days [ Time Frame: 21 days ]
    Ventilator support (IMV or NIV or CPAP) free days (VSFD) at day 21

  11. Length of ICU stay [ Time Frame: 3 months ]
    Length of intensive care unit stay

  12. Number of days hospitalised [ Time Frame: 3 months ]
    Number of days hospitalised

  13. Mortality [ Time Frame: 28 days ]
    Mortality at day 28



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years old
  • Confirmed COVID-19 positive by PCR
  • Within 24 hours of mechanical ventilation (ETI arm) or within 24 hours of needing either CPAP or NIV (CPAP/NIV arm)
  • Assent or professional assent obtained

Exclusion Criteria:

  • Imminent expected death within 24 hours
  • Specific contraindications to surfactant administration (e.g. known allergy, pneumothorax, pulmonary haemorrhage)
  • Known or suspected pregnancy
  • Stage 4 severe chronic kidney disease or requiring dialysis (i.e., eGFR < 30)
  • Liver failure
  • Anticipated transfer to another hospital, which is not a study site within 72 hours.
  • Current participation or participation in another study within the last month that in the opinion of the investigator would prevent enrollment for safety purposes.
  • Consent Declined

Information from the National Library of Medicine

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): NCT04362059


Locations
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United Kingdom
University Hospital Southampton NHS Foundation Trust
Southampton, Hampshire, United Kingdom, SO16 6YD
University College London Hospitals NHS Foundation Trust
London, United Kingdom, NW1 2BU
Sponsors and Collaborators
University Hospital Southampton NHS Foundation Trust
Bill and Melinda Gates Foundation
University College, London
Investigators
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Principal Investigator: Michael P Grocott, MD University Hospital Southampton NHS Foundation Trust
Additional Information:
Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Hospital Southampton NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT04362059    
Other Study ID Numbers: RHM CRI0399
First Posted: April 24, 2020    Key Record Dates
Last Update Posted: September 29, 2023
Last Verified: September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Respiratory Tract Infections
Infections
Respiratory Tract Diseases