Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial
Objective To evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial).Design Open label, randomised clinical trial.Setting CORIMUNO-19 cohort (publicly supported platform o...
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2023-10-01
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| author | Arsène Mekinian Xavier Mariette Florence Ader Raphaël Porcher Philippe Ravaud Lionel Piroth Gabriel Baron Jean-Marie Michot Karine Lacombe Tabassome Simon Sophie Georgin-Lavialle Charles Cazanave Marc Michel Olivier Hermine Guillaume Martin-Blondel Fabrice Bonnet Pierre Tiberghien Xavier Lescure Xavier de Lamballerie Valérie Pourcher Matthieu Resche-Rigon Thibault Chiarabini Stella Rousset Fanny Pommeret Thomas Hueso Julien Saison Nathalie De Castro Anne Francois Pascal Morel Nora Soussi Phillipe Brun Pierre Sellier Pierre-Louis Tharaux |
| author_facet | Arsène Mekinian Xavier Mariette Florence Ader Raphaël Porcher Philippe Ravaud Lionel Piroth Gabriel Baron Jean-Marie Michot Karine Lacombe Tabassome Simon Sophie Georgin-Lavialle Charles Cazanave Marc Michel Olivier Hermine Guillaume Martin-Blondel Fabrice Bonnet Pierre Tiberghien Xavier Lescure Xavier de Lamballerie Valérie Pourcher Matthieu Resche-Rigon Thibault Chiarabini Stella Rousset Fanny Pommeret Thomas Hueso Julien Saison Nathalie De Castro Anne Francois Pascal Morel Nora Soussi Phillipe Brun Pierre Sellier Pierre-Louis Tharaux |
| author_sort | Arsène Mekinian |
| collection | DOAJ |
| description | Objective To evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial).Design Open label, randomised clinical trial.Setting CORIMUNO-19 cohort (publicly supported platform of open label, randomised controlled trials of immune modulatory drugs in patients admitted to hospital with moderate or severe covid-19 disease) based on 19 university and general hospitals across France, from 16 April 2020 to 21 April 2021.Participants 120 adults (n=60 in the covid-19 convalescent plasma group, n=60 in the usual care group) admitted to hospital with a positive SARS-CoV2 test result, duration of symptoms <9 days, and World Health Organization score of 4 or 5. 49 patients (n=22, n=27) had underlying immunosuppression.Interventions Open label randomisation to usual care or four units (200-220 mL/unit, 2 units/day over two consecutive days) of covid-19 convalescent plasma with a seroneutralisation titre >40.Main outcome measures Primary outcomes were proportion of patients with a WHO Clinical Progression Scale score of ≥6 on the 10 point scale on day 4 (higher values indicate a worse outcome), and survival without assisted ventilation or additional immunomodulatory treatment by day 14. Secondary outcomes were changes in WHO Clinical Progression Scale scores, overall survival, time to discharge, and time to end of dependence on oxygen supply. Predefined subgroups analyses included immunosuppression status, duration of symptoms before randomisation, and use of steroids.Results 120 patients were recruited and assigned to covid-19 convalescent plasma (n=60) or usual care (n=60), including 22 (covid-19 convalescent plasma) and 27 (usual care) patients who were immunocompromised. 13 (22%) patients who received convalescent plasma had a WHO Clinical Progression Scale score of ≥6 at day 4 versus eight (13%) patients who received usual care (adjusted odds ratio 1.88, 95% credible interval 0.71 to 5.24). By day 14, 19 (31.6%) patients in the convalescent plasma group and 20 (33.3%) patients in the usual care group needed ventilation, additional immunomodulatory treatment, or had died. For cumulative incidence of death, three (5%) patients in the convalescent plasma group and eight (13%) in the usual care group died by day 14 (adjusted hazard ratio 0.40, 95% confidence interval 0.10 to 1.53), and seven (12%) patients in the convalescent plasma group and 12 (20%) in the usual care group by day 28 (adjusted hazard ratio 0.51, 0.20 to 1.32). In a subgroup analysis performed in patients who were immunocompromised, transfusion of covid-19 convalescent plasma was associated with mortality (hazard ratio 0.39, 95% confidence interval 0.14 to 1.10).Conclusions In this study, covid-19 convalescent plasma did not improve early outcomes in patients with moderate covid-19 disease. The efficacy of convalescent plasma in patients who are immunocompromised should be investigated further.Trial registration ClinicalTrials.gov NCT04345991. |
| format | Article |
| id | doaj-art-9b4f2b3859614bc9b04b49cd568d1cb6 |
| institution | DOAJ |
| issn | 2754-0413 |
| language | English |
| publishDate | 2023-10-01 |
| publisher | BMJ Publishing Group |
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| spelling | doaj-art-9b4f2b3859614bc9b04b49cd568d1cb62025-08-20T03:09:45ZengBMJ Publishing GroupBMJ Medicine2754-04132023-10-012110.1136/bmjmed-2022-000427Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trialArsène Mekinian0Xavier Mariette1Florence Ader2Raphaël Porcher3Philippe Ravaud4Lionel Piroth5Gabriel Baron6Jean-Marie Michot7Karine Lacombe8Tabassome Simon9Sophie Georgin-Lavialle10Charles Cazanave11Marc Michel12Olivier Hermine13Guillaume Martin-Blondel14Fabrice Bonnet15Pierre Tiberghien16Xavier Lescure17Xavier de Lamballerie18Valérie Pourcher19Matthieu Resche-Rigon20Thibault Chiarabini21Stella Rousset22Fanny Pommeret23Thomas Hueso24Julien Saison25Nathalie De Castro26Anne Francois27Pascal Morel28Nora Soussi29Phillipe Brun30Pierre Sellier31Pierre-Louis Tharaux32Department of Internal Medicine, Sorbonne University, DMU i3D, Saint-Antoine Hospital, Paris, FranceDepartment of Rheumatology, Université Paris-Saclay, AP-HP-Hôpital Bicêtre, Paris, FranceCIRI, INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Lyon, FranceUniversité Paris Cité and Université Sorbonne Paris Nord, Inserm, INRAe, Centre for Research in Epidemiology and Statistics (CRESS), Paris, FranceprofessorInfectious Diseases Department, University Hospital Centre Dijon Bourgogne, Dijon, FrancestatisticianPalliative Care Unit, Gustave Roussy Institute, Villejuif, France2 Sorbonne University, Paris, FranceSorbonne Université, Paris, FranceSorbonne Université, Paris, FranceInfectious Diseases Department, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, FranceUniversité de Paris Est Créteil, Créteil, FranceHematology, Hopital Necker-Enfants Malades, Paris, France3 Infectious and Tropical Diseases, Centre Hospitalier Universitaire de Toulouse, Toulouse, FranceDepartment of Diabetology, CHU de Rennes, Rennes, FranceEtablissement Francais du Sang, La Plaine Saint-Denis, FranceUniversité de Paris, Paris, FranceUnité des Virus Émergents, IRD 190-Inserm 1207, Aix-Marseille University, Marseille, FranceSorbonne Université, Paris, FranceCentre of Epidemiological Research and Statistics Paris Cité (CRESS - U1153), Paris, FranceInfectious Diseases Department, St Antoine Hospital, AP-HP, Paris, FranceInfectious Diseases department, Centre Hospitalier Universitaire de Toulouse, Toulouse, FranceOncology Department, Institut Gustave Roussy, Villejuif, FranceHematology department, Avicenne Hospital, AP-HP, Bobigny, FranceInfectious Diseases Department, Centre Hospitalier de Valence, Valence, FranceUniversité de Bordeaux, Bordeaux, FranceEtablissement Francais du Sang, La Plaine Saint-Denis, FranceEtablissement Francais du Sang, La Plaine Saint-Denis, FranceClinical Research Platform (URC-CRC-CRB), Saint-Antoine Hospital, AP-HP, Paris, FranceCentre Hospitalier de Valence, Valence, FranceInfectious Diseases Department, Lariboisière Hospital, AP-HP, Paris, FranceParis Cardiovascular Centre – PARCC, Inserm, Université Paris-Cité, Paris, FranceObjective To evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial).Design Open label, randomised clinical trial.Setting CORIMUNO-19 cohort (publicly supported platform of open label, randomised controlled trials of immune modulatory drugs in patients admitted to hospital with moderate or severe covid-19 disease) based on 19 university and general hospitals across France, from 16 April 2020 to 21 April 2021.Participants 120 adults (n=60 in the covid-19 convalescent plasma group, n=60 in the usual care group) admitted to hospital with a positive SARS-CoV2 test result, duration of symptoms <9 days, and World Health Organization score of 4 or 5. 49 patients (n=22, n=27) had underlying immunosuppression.Interventions Open label randomisation to usual care or four units (200-220 mL/unit, 2 units/day over two consecutive days) of covid-19 convalescent plasma with a seroneutralisation titre >40.Main outcome measures Primary outcomes were proportion of patients with a WHO Clinical Progression Scale score of ≥6 on the 10 point scale on day 4 (higher values indicate a worse outcome), and survival without assisted ventilation or additional immunomodulatory treatment by day 14. Secondary outcomes were changes in WHO Clinical Progression Scale scores, overall survival, time to discharge, and time to end of dependence on oxygen supply. Predefined subgroups analyses included immunosuppression status, duration of symptoms before randomisation, and use of steroids.Results 120 patients were recruited and assigned to covid-19 convalescent plasma (n=60) or usual care (n=60), including 22 (covid-19 convalescent plasma) and 27 (usual care) patients who were immunocompromised. 13 (22%) patients who received convalescent plasma had a WHO Clinical Progression Scale score of ≥6 at day 4 versus eight (13%) patients who received usual care (adjusted odds ratio 1.88, 95% credible interval 0.71 to 5.24). By day 14, 19 (31.6%) patients in the convalescent plasma group and 20 (33.3%) patients in the usual care group needed ventilation, additional immunomodulatory treatment, or had died. For cumulative incidence of death, three (5%) patients in the convalescent plasma group and eight (13%) in the usual care group died by day 14 (adjusted hazard ratio 0.40, 95% confidence interval 0.10 to 1.53), and seven (12%) patients in the convalescent plasma group and 12 (20%) in the usual care group by day 28 (adjusted hazard ratio 0.51, 0.20 to 1.32). In a subgroup analysis performed in patients who were immunocompromised, transfusion of covid-19 convalescent plasma was associated with mortality (hazard ratio 0.39, 95% confidence interval 0.14 to 1.10).Conclusions In this study, covid-19 convalescent plasma did not improve early outcomes in patients with moderate covid-19 disease. The efficacy of convalescent plasma in patients who are immunocompromised should be investigated further.Trial registration ClinicalTrials.gov NCT04345991.https://bmjmedicine.bmj.com/content/2/1/e000427.full |
| spellingShingle | Arsène Mekinian Xavier Mariette Florence Ader Raphaël Porcher Philippe Ravaud Lionel Piroth Gabriel Baron Jean-Marie Michot Karine Lacombe Tabassome Simon Sophie Georgin-Lavialle Charles Cazanave Marc Michel Olivier Hermine Guillaume Martin-Blondel Fabrice Bonnet Pierre Tiberghien Xavier Lescure Xavier de Lamballerie Valérie Pourcher Matthieu Resche-Rigon Thibault Chiarabini Stella Rousset Fanny Pommeret Thomas Hueso Julien Saison Nathalie De Castro Anne Francois Pascal Morel Nora Soussi Phillipe Brun Pierre Sellier Pierre-Louis Tharaux Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial BMJ Medicine |
| title | Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial |
| title_full | Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial |
| title_fullStr | Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial |
| title_full_unstemmed | Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial |
| title_short | Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial |
| title_sort | use of covid 19 convalescent plasma to treat patients admitted to hospital for covid 19 with or without underlying immunodeficiency open label randomised clinical trial |
| url | https://bmjmedicine.bmj.com/content/2/1/e000427.full |
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