Clinical trial NCT04362059: A Clinical Trial of Nebulized Surfactant for the Treatment of Moderate to Severe COVID-19
Official title: A Clinical Trial of Nebulized Surfactant for the Treatment of Moderate to Severe COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Respiratory Infections
Lead sponsor: University Hospital Southampton NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
name: University College, London
First posted: 2020-04-24
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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

Primary outcomes:
measure: Oxygenation Improvement
timeFrame: 3 months
measure: Pulmonary ventilation Improvement
timeFrame: 3 months
measure: IMV Need
timeFrame: 3 months
Secondary outcomes:
measure: Safety Assessment of Frequency and Severity of Adverse Events
timeFrame: 3 months
measure: Change in PaO2/FiO2 ratio
timeFrame: 3 months
measure: Mean Change in ventilatory index
timeFrame: 48 hours
measure: Mean Change in pulmonary compliance
timeFrame: 48 hours
measure: Mean Change in PEEP requirement
timeFrame: 48 Hours
measure: Clinical Improvement
timeFrame: 28 days
measure: Mechanical ventilation duration
timeFrame: 3 months
measure: Duration of days
timeFrame: 3 months
measure: IMV free days
timeFrame: 21 days
measure: Ventilator support free days
timeFrame: 21 days
measure: Length of ICU stay
timeFrame: 3 months
measure: Number of days hospitalised
timeFrame: 3 months
measure: Mortality
timeFrame: 28 days
Other outcomes:
Locations:
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
Study officials:
affiliation: University Hospital Southampton NHS Foundation Trust
name: Michael P Grocott, MD
role: PRINCIPAL_INVESTIGATOR
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