Can nebulised heparin reduce acute lung injury in patients with SARS‑CoV‑2 requiring advanced respiratory support in Ireland: the CHARTER‑Ireland phase Ib/IIa, randomised, parallel-group, open-label study
Abstract Background Nebulised unfractionated heparin may attenuate COVID-19 ARDS by reducing pulmonary microvascular thrombosis, blocking SARS-CoV-2 entry into cells, and decreasing lung inflammation. COVID-19 patients with a raised d-dimer have areas of pulmonary hypoperfusion on CT perfusion scans...
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SpringerOpen
2025-02-01
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| Series: | Intensive Care Medicine Experimental |
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| Online Access: | https://doi.org/10.1186/s40635-025-00727-x |
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| author | David Cosgrave Bairbre McNicholas Ciara Hanley John Robert Sheehan Padraig Calpin Maeve Kernan Darragh Murphy Alberto Alvarez‑Iglesias John Ferguson Camilla Giacomini Christine Greene Catriona Cody Shane McGeary Marion Murphy Marianne Fitzgerald Gerard Curley Barry Dixon Roger J. Smith Claire Masterson Daniel O’Toole Frank van Haren John G. Laffey |
| author_facet | David Cosgrave Bairbre McNicholas Ciara Hanley John Robert Sheehan Padraig Calpin Maeve Kernan Darragh Murphy Alberto Alvarez‑Iglesias John Ferguson Camilla Giacomini Christine Greene Catriona Cody Shane McGeary Marion Murphy Marianne Fitzgerald Gerard Curley Barry Dixon Roger J. Smith Claire Masterson Daniel O’Toole Frank van Haren John G. Laffey |
| author_sort | David Cosgrave |
| collection | DOAJ |
| description | Abstract Background Nebulised unfractionated heparin may attenuate COVID-19 ARDS by reducing pulmonary microvascular thrombosis, blocking SARS-CoV-2 entry into cells, and decreasing lung inflammation. COVID-19 patients with a raised d-dimer have areas of pulmonary hypoperfusion on CT perfusion scans of the lung and have increased mortality risk. Methods This was a phase Ib/IIa open-label multi-centre, randomised controlled trial. The study was designed to evaluate whether nebulised unfractionated heparin decreased d-dimer concentrations, with safety as a co-primary outcome. Results Forty patients were recruited, with 20 patients into each group. Mean age was 56.6 (SD 11.5) in the heparin group and 51.3 (SD 14.7) in the standard care group, while 60% of participants were male. There was no change in d-dimers from baseline to day 10 (heparin group mean change − 316.5, [SD 1840.3] and control group mean change − 321.7 [SD 3589.4]; p = 0.996). Fourteen patients suffered at least one serious adverse event, 9 patients the Heparin group and 5 in the control group. Eight patients had one or more bleeding events, 5 in the heparin group and 3 in the control group, but were no cases of pulmonary bleeding, of severe haemorrhage or of heparin-induced thrombocytopenia. Patients receiving heparin therapy had lower PaO2/FiO2 ratios, increased oxygenation indices, and decreased ROX index profiles, up to day 10. The time to separation from respiratory support, and the time to ICU or hospital discharge was similar in both groups. There were 3 deaths in the Heparin group and 2 in the control group. Conclusions Nebulised unfractionated heparin was safe and well tolerated, but did not reduce d-dimer concentrations, and worsened oxygenation indices in patients with COVID-19 ARDS. |
| format | Article |
| id | doaj-art-16b7b3ae9deb453eaddfc7a230180363 |
| institution | Kabale University |
| issn | 2197-425X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Intensive Care Medicine Experimental |
| spelling | doaj-art-16b7b3ae9deb453eaddfc7a2301803632025-02-09T12:04:35ZengSpringerOpenIntensive Care Medicine Experimental2197-425X2025-02-0113111110.1186/s40635-025-00727-xCan nebulised heparin reduce acute lung injury in patients with SARS‑CoV‑2 requiring advanced respiratory support in Ireland: the CHARTER‑Ireland phase Ib/IIa, randomised, parallel-group, open-label studyDavid Cosgrave0Bairbre McNicholas1Ciara Hanley2John Robert Sheehan3Padraig Calpin4Maeve Kernan5Darragh Murphy6Alberto Alvarez‑Iglesias7John Ferguson8Camilla Giacomini9Christine Greene10Catriona Cody11Shane McGeary12Marion Murphy13Marianne Fitzgerald14Gerard Curley15Barry Dixon16Roger J. Smith17Claire Masterson18Daniel O’Toole19Frank van Haren20John G. Laffey21Department of Anaesthesia and Intensive Care Medicine, University Hospital GalwayDepartment of Anaesthesia and Intensive Care Medicine, University Hospital GalwayDepartment of Anaesthesia and Intensive Care Medicine, University Hospital GalwayDepartment of Anaesthesia and Intensive Care Medicine, University Hospital GalwayDepartment of Anaesthesia and Intensive Care Medicine, University Hospital GalwayAnaesthesia and Intensive Care Medicine, School of Medicine, University of GalwayAnaesthesia and Intensive Care Medicine, School of Medicine, University of GalwayHRB Clinical Research Facility, School of Medicine, University of GalwayHRB Clinical Research Facility, School of Medicine, University of GalwayDepartment of Anaesthesia and Intensive Care Medicine, University Hospital GalwayDepartment of Anaesthesia and Intensive Care Medicine, Connolly Memorial Hospital BlanchardstownDepartment of Anaesthesia and Intensive Care Medicine, Connolly Memorial Hospital BlanchardstownDepartment of Anaesthesia and Intensive Care Medicine, Connolly Memorial Hospital BlanchardstownDepartment of Anaesthesia and Intensive Care Medicine, University Hospital GalwayDepartment of Anaesthesia and Intensive Care Medicine, Limerick University HospitalDepartment of Anaesthesia and Intensive Care Medicine, Royal College of Surgeons in Ireland, Beaumont HospitalDepartment of Critical Care Medicine, St Vincent’s Hospital MelbourneDepartment of Critical Care Medicine, St Vincent’s Hospital MelbourneAnaesthesia and Intensive Care Medicine, School of Medicine, University of GalwayAnaesthesia and Intensive Care Medicine, School of Medicine, University of GalwayIntensive Care Unit, St George HospitalDepartment of Anaesthesia and Intensive Care Medicine, University Hospital GalwayAbstract Background Nebulised unfractionated heparin may attenuate COVID-19 ARDS by reducing pulmonary microvascular thrombosis, blocking SARS-CoV-2 entry into cells, and decreasing lung inflammation. COVID-19 patients with a raised d-dimer have areas of pulmonary hypoperfusion on CT perfusion scans of the lung and have increased mortality risk. Methods This was a phase Ib/IIa open-label multi-centre, randomised controlled trial. The study was designed to evaluate whether nebulised unfractionated heparin decreased d-dimer concentrations, with safety as a co-primary outcome. Results Forty patients were recruited, with 20 patients into each group. Mean age was 56.6 (SD 11.5) in the heparin group and 51.3 (SD 14.7) in the standard care group, while 60% of participants were male. There was no change in d-dimers from baseline to day 10 (heparin group mean change − 316.5, [SD 1840.3] and control group mean change − 321.7 [SD 3589.4]; p = 0.996). Fourteen patients suffered at least one serious adverse event, 9 patients the Heparin group and 5 in the control group. Eight patients had one or more bleeding events, 5 in the heparin group and 3 in the control group, but were no cases of pulmonary bleeding, of severe haemorrhage or of heparin-induced thrombocytopenia. Patients receiving heparin therapy had lower PaO2/FiO2 ratios, increased oxygenation indices, and decreased ROX index profiles, up to day 10. The time to separation from respiratory support, and the time to ICU or hospital discharge was similar in both groups. There were 3 deaths in the Heparin group and 2 in the control group. Conclusions Nebulised unfractionated heparin was safe and well tolerated, but did not reduce d-dimer concentrations, and worsened oxygenation indices in patients with COVID-19 ARDS.https://doi.org/10.1186/s40635-025-00727-xHeparinNebulisedAerosol deliveryCOVID-19Acute respiratory distress syndromeSafety study |
| spellingShingle | David Cosgrave Bairbre McNicholas Ciara Hanley John Robert Sheehan Padraig Calpin Maeve Kernan Darragh Murphy Alberto Alvarez‑Iglesias John Ferguson Camilla Giacomini Christine Greene Catriona Cody Shane McGeary Marion Murphy Marianne Fitzgerald Gerard Curley Barry Dixon Roger J. Smith Claire Masterson Daniel O’Toole Frank van Haren John G. Laffey Can nebulised heparin reduce acute lung injury in patients with SARS‑CoV‑2 requiring advanced respiratory support in Ireland: the CHARTER‑Ireland phase Ib/IIa, randomised, parallel-group, open-label study Intensive Care Medicine Experimental Heparin Nebulised Aerosol delivery COVID-19 Acute respiratory distress syndrome Safety study |
| title | Can nebulised heparin reduce acute lung injury in patients with SARS‑CoV‑2 requiring advanced respiratory support in Ireland: the CHARTER‑Ireland phase Ib/IIa, randomised, parallel-group, open-label study |
| title_full | Can nebulised heparin reduce acute lung injury in patients with SARS‑CoV‑2 requiring advanced respiratory support in Ireland: the CHARTER‑Ireland phase Ib/IIa, randomised, parallel-group, open-label study |
| title_fullStr | Can nebulised heparin reduce acute lung injury in patients with SARS‑CoV‑2 requiring advanced respiratory support in Ireland: the CHARTER‑Ireland phase Ib/IIa, randomised, parallel-group, open-label study |
| title_full_unstemmed | Can nebulised heparin reduce acute lung injury in patients with SARS‑CoV‑2 requiring advanced respiratory support in Ireland: the CHARTER‑Ireland phase Ib/IIa, randomised, parallel-group, open-label study |
| title_short | Can nebulised heparin reduce acute lung injury in patients with SARS‑CoV‑2 requiring advanced respiratory support in Ireland: the CHARTER‑Ireland phase Ib/IIa, randomised, parallel-group, open-label study |
| title_sort | can nebulised heparin reduce acute lung injury in patients with sars cov 2 requiring advanced respiratory support in ireland the charter ireland phase ib iia randomised parallel group open label study |
| topic | Heparin Nebulised Aerosol delivery COVID-19 Acute respiratory distress syndrome Safety study |
| url | https://doi.org/10.1186/s40635-025-00727-x |
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