A randomized controlled trial of nebulized surfactant for the treatment of severe COVID-19 in adults (COVSurf trial)
Abstract SARS-CoV-2 directly targets alveolar epithelial cells and can lead to surfactant deficiency. Early reports suggested surfactant replacement may be effective in improving outcomes. The aim of the study to assess the feasibility and efficacy of nebulized surfactant in mechanically ventilated...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-47672-x |
| _version_ | 1827603773904650240 |
|---|---|
| author | Ahilanandan Dushianthan Howard W. Clark David Brealey Danny Pratt James B. Fink Jens Madsen Helen Moyses Lewis Matthews Tracy Hussell Ratko Djukanovic Martin Feelisch Anthony D. Postle Michael P. W. Grocott |
| author_facet | Ahilanandan Dushianthan Howard W. Clark David Brealey Danny Pratt James B. Fink Jens Madsen Helen Moyses Lewis Matthews Tracy Hussell Ratko Djukanovic Martin Feelisch Anthony D. Postle Michael P. W. Grocott |
| author_sort | Ahilanandan Dushianthan |
| collection | DOAJ |
| description | Abstract SARS-CoV-2 directly targets alveolar epithelial cells and can lead to surfactant deficiency. Early reports suggested surfactant replacement may be effective in improving outcomes. The aim of the study to assess the feasibility and efficacy of nebulized surfactant in mechanically ventilated COVID-19 patients. Patients were randomly assigned to receive open-labelled bovine nebulized surfactant or control (ratio 3-surfactant: 2-control). This was an exploratory dose–response study starting with 1080 mg of surfactant delivered at 3 time points (0, 8 and 24 h). After completion of 10 patients, the dose was reduced to 540 mg, and the frequency of nebulization was increased to 5/6 time points (0, 12, 24, 36, 48, and an optional 72 h) on the advice of the Trial Steering Committee. The co-primary outcomes were improvement in oxygenation (change in PaO2/FiO2 ratio) and ventilation index at 48 h. 20 patients were recruited (12 surfactant and 8 controls). Demographic and clinical characteristics were similar between groups at presentation. Nebulized surfactant administration was feasible. There was no significant improvement in oxygenation at 48 h overall. There were also no differences in secondary outcomes or adverse events. Nebulized surfactant administration is feasible in mechanically ventilated patients with COVID-19 but did not improve measures of oxygenation or ventilation. |
| first_indexed | 2024-03-09T05:45:18Z |
| format | Article |
| id | doaj.art-a77d36c23f7d4e1287d0bc5878c169f2 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T05:45:18Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a77d36c23f7d4e1287d0bc5878c169f22023-12-03T12:21:32ZengNature PortfolioScientific Reports2045-23222023-11-0113111210.1038/s41598-023-47672-xA randomized controlled trial of nebulized surfactant for the treatment of severe COVID-19 in adults (COVSurf trial)Ahilanandan Dushianthan0Howard W. Clark1David Brealey2Danny Pratt3James B. Fink4Jens Madsen5Helen Moyses6Lewis Matthews7Tracy Hussell8Ratko Djukanovic9Martin Feelisch10Anthony D. Postle11Michael P. W. Grocott12Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of SouthamptonUniversity College London HospitalUniversity College London HospitalSouthampton NIHR Clinical Research Facility, University Hospital SouthamptonAerogen Pharma CorporationUniversity College London HospitalPerioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of SouthamptonPerioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of SouthamptonLydia Becker Institute of Immunology and Inflammation, University of ManchesterPerioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of SouthamptonPerioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of SouthamptonPerioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of SouthamptonPerioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of SouthamptonAbstract SARS-CoV-2 directly targets alveolar epithelial cells and can lead to surfactant deficiency. Early reports suggested surfactant replacement may be effective in improving outcomes. The aim of the study to assess the feasibility and efficacy of nebulized surfactant in mechanically ventilated COVID-19 patients. Patients were randomly assigned to receive open-labelled bovine nebulized surfactant or control (ratio 3-surfactant: 2-control). This was an exploratory dose–response study starting with 1080 mg of surfactant delivered at 3 time points (0, 8 and 24 h). After completion of 10 patients, the dose was reduced to 540 mg, and the frequency of nebulization was increased to 5/6 time points (0, 12, 24, 36, 48, and an optional 72 h) on the advice of the Trial Steering Committee. The co-primary outcomes were improvement in oxygenation (change in PaO2/FiO2 ratio) and ventilation index at 48 h. 20 patients were recruited (12 surfactant and 8 controls). Demographic and clinical characteristics were similar between groups at presentation. Nebulized surfactant administration was feasible. There was no significant improvement in oxygenation at 48 h overall. There were also no differences in secondary outcomes or adverse events. Nebulized surfactant administration is feasible in mechanically ventilated patients with COVID-19 but did not improve measures of oxygenation or ventilation.https://doi.org/10.1038/s41598-023-47672-x |
| spellingShingle | Ahilanandan Dushianthan Howard W. Clark David Brealey Danny Pratt James B. Fink Jens Madsen Helen Moyses Lewis Matthews Tracy Hussell Ratko Djukanovic Martin Feelisch Anthony D. Postle Michael P. W. Grocott A randomized controlled trial of nebulized surfactant for the treatment of severe COVID-19 in adults (COVSurf trial) Scientific Reports |
| title | A randomized controlled trial of nebulized surfactant for the treatment of severe COVID-19 in adults (COVSurf trial) |
| title_full | A randomized controlled trial of nebulized surfactant for the treatment of severe COVID-19 in adults (COVSurf trial) |
| title_fullStr | A randomized controlled trial of nebulized surfactant for the treatment of severe COVID-19 in adults (COVSurf trial) |
| title_full_unstemmed | A randomized controlled trial of nebulized surfactant for the treatment of severe COVID-19 in adults (COVSurf trial) |
| title_short | A randomized controlled trial of nebulized surfactant for the treatment of severe COVID-19 in adults (COVSurf trial) |
| title_sort | randomized controlled trial of nebulized surfactant for the treatment of severe covid 19 in adults covsurf trial |
| url | https://doi.org/10.1038/s41598-023-47672-x |
| work_keys_str_mv | AT ahilanandandushianthan arandomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT howardwclark arandomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT davidbrealey arandomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT dannypratt arandomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT jamesbfink arandomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT jensmadsen arandomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT helenmoyses arandomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT lewismatthews arandomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT tracyhussell arandomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT ratkodjukanovic arandomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT martinfeelisch arandomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT anthonydpostle arandomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT michaelpwgrocott arandomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT ahilanandandushianthan randomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT howardwclark randomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT davidbrealey randomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT dannypratt randomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT jamesbfink randomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT jensmadsen randomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT helenmoyses randomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT lewismatthews randomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT tracyhussell randomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT ratkodjukanovic randomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT martinfeelisch randomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT anthonydpostle randomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial AT michaelpwgrocott randomizedcontrolledtrialofnebulizedsurfactantforthetreatmentofseverecovid19inadultscovsurftrial |