ImmunoSep (Personalised Immunotherapy in Sepsis) international double-blind, double-dummy, placebo-controlled randomised clinical trial: study protocol
Introduction Sepsis is a major cause of death among hospitalised patients. Accumulating evidence suggests that immune response during sepsis cascade lies within a spectrum of dysregulated host responses. On the one side of the spectrum there are patients whose response is characterised by fulminant...
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BMJ Publishing Group
2022-12-01
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| Online Access: | https://bmjopen.bmj.com/content/12/12/e067251.full |
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| author | Peter Pickkers Evangelos J Giamarellos-Bourboulis Mihai G Netea Michael Bauer Mihaela Lupse Frank Bloos Tom van der Poll W Joost Wiersinga Thierry Calandra Sylvain Meylan Alexander P J Vlaar Sebastian Weis Marleen A Slim Niels van Mourik Marcella C A Müller Antigone Kotsaki Lonneke van Vught Aline de Nooijer Lieke Bakkerus Nikolaos Antonakos |
| author_facet | Peter Pickkers Evangelos J Giamarellos-Bourboulis Mihai G Netea Michael Bauer Mihaela Lupse Frank Bloos Tom van der Poll W Joost Wiersinga Thierry Calandra Sylvain Meylan Alexander P J Vlaar Sebastian Weis Marleen A Slim Niels van Mourik Marcella C A Müller Antigone Kotsaki Lonneke van Vught Aline de Nooijer Lieke Bakkerus Nikolaos Antonakos |
| author_sort | Peter Pickkers |
| collection | DOAJ |
| description | Introduction Sepsis is a major cause of death among hospitalised patients. Accumulating evidence suggests that immune response during sepsis cascade lies within a spectrum of dysregulated host responses. On the one side of the spectrum there are patients whose response is characterised by fulminant hyperinflammation or macrophage activation-like syndrome (MALS), and on the other side patients whose immune response is characterised by immunoparalysis. A sizeable group of patients are situated between the two extremes. Recognising immune endotype is very important in order to choose the appropriate immunotherapeutic approach for each patient resulting in the best chance to improve the outcome.Methods and analysis ImmunoSep is a randomised placebo-controlled phase 2 clinical trial with a double-dummy design in which the effect of precision immunotherapy on sepsis phenotypes with MALS and immunoparalysis is studied. Patients are stratified using biomarkers. Specifically, 280 patients will be 1:1 randomly assigned to placebo or active immunotherapy as adjunct to standard-of-care treatment. In the active immunotherapy arm, patients with MALS will receive anakinra (recombinant interleukin-1 receptor antagonist) intravenously, and patients with immunoparalysis will receive subcutaneous recombinant human interferon-gamma. Τhe primary endpoint is the comparative decrease of the mean total Sequential Organ Failure Assessment score by at least 1.4 points by day 9 from randomisation.Ethics and dissemination The protocol is approved by the German Federal Institute for Drugs and Medical Devices; the National Ethics Committee of Greece and by the National Organization for Medicines of Greece; the Central Committee on Research Involving Human Subjects and METC Oost Netherland for the Netherlands; the National Agency for Medicine and Medical Products of Romania; and the Commission Cantonale d’éthique de la recherche sur l’être human of Switzerland. The results will be submitted for publication in peer-reviewed journals.Trial registration number NCT04990232. |
| format | Article |
| id | doaj-art-dd79ea861b0c44379d15aaec6632016d |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | BMJ Publishing Group |
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| spelling | doaj-art-dd79ea861b0c44379d15aaec6632016d2025-08-20T02:14:34ZengBMJ Publishing GroupBMJ Open2044-60552022-12-01121210.1136/bmjopen-2022-067251ImmunoSep (Personalised Immunotherapy in Sepsis) international double-blind, double-dummy, placebo-controlled randomised clinical trial: study protocolPeter Pickkers0Evangelos J Giamarellos-Bourboulis1Mihai G Netea2Michael Bauer3Mihaela Lupse4Frank Bloos5Tom van der Poll6W Joost Wiersinga7Thierry Calandra8Sylvain Meylan9Alexander P J Vlaar10Sebastian Weis11Marleen A Slim12Niels van Mourik13Marcella C A Müller14Antigone Kotsaki15Lonneke van Vught16Aline de Nooijer17Lieke Bakkerus18Nikolaos Antonakos19Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, GreeceInternal Medicine, Radboud University Medical Center, Nijmegen, The NetherlandsDepartment of Anaesthesiology and Critical Care Medicine, Jena University Hospital – Friedrich Schiller University of Jena, Jena, Thuringia, GermanyDepartment of Internal Medicine, University of Cluj-Napoca, Cluj, RomaniaSMITH consortium of the German Medical Informatics Initiative, Leipzig, Germany2 Center for Experimental and Molecular Medicine, Amsterdam UMC Location AMC, Amsterdam, The NetherlandsDepartment of Internal Medicine, Amsterdam University Medical Centres, Duivendrecht, The NetherlandsInfectious Diseases Service, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandInfectious Diseases Service, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandDepartment of Intensive Care, Amsterdam UMC Locatie AMC, Amsterdam, NetherlandsCenter for Infectious Disease and Infection Control, Jena University Hospital, Jena, Germany1 Intensive Care, Amsterdam UMC Location AMC, Amsterdam, The Netherlands2 Center for Experimental and Molecular Medicine, Amsterdam UMC Location AMC, Amsterdam, The Netherlands1 Intensive Care, Amsterdam UMC Location AMC, Amsterdam, The Netherlands4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Infectious Diseases, Amsterdam University Medical Center, Amsterdam, The NetherlandsDepartment of Internal Medicine and Infectious Diseases, Radboud University Medical Center, Nijmegen, The NetherlandsDepartment of Internal Medicine and Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, GreeceIntroduction Sepsis is a major cause of death among hospitalised patients. Accumulating evidence suggests that immune response during sepsis cascade lies within a spectrum of dysregulated host responses. On the one side of the spectrum there are patients whose response is characterised by fulminant hyperinflammation or macrophage activation-like syndrome (MALS), and on the other side patients whose immune response is characterised by immunoparalysis. A sizeable group of patients are situated between the two extremes. Recognising immune endotype is very important in order to choose the appropriate immunotherapeutic approach for each patient resulting in the best chance to improve the outcome.Methods and analysis ImmunoSep is a randomised placebo-controlled phase 2 clinical trial with a double-dummy design in which the effect of precision immunotherapy on sepsis phenotypes with MALS and immunoparalysis is studied. Patients are stratified using biomarkers. Specifically, 280 patients will be 1:1 randomly assigned to placebo or active immunotherapy as adjunct to standard-of-care treatment. In the active immunotherapy arm, patients with MALS will receive anakinra (recombinant interleukin-1 receptor antagonist) intravenously, and patients with immunoparalysis will receive subcutaneous recombinant human interferon-gamma. Τhe primary endpoint is the comparative decrease of the mean total Sequential Organ Failure Assessment score by at least 1.4 points by day 9 from randomisation.Ethics and dissemination The protocol is approved by the German Federal Institute for Drugs and Medical Devices; the National Ethics Committee of Greece and by the National Organization for Medicines of Greece; the Central Committee on Research Involving Human Subjects and METC Oost Netherland for the Netherlands; the National Agency for Medicine and Medical Products of Romania; and the Commission Cantonale d’éthique de la recherche sur l’être human of Switzerland. The results will be submitted for publication in peer-reviewed journals.Trial registration number NCT04990232.https://bmjopen.bmj.com/content/12/12/e067251.full |
| spellingShingle | Peter Pickkers Evangelos J Giamarellos-Bourboulis Mihai G Netea Michael Bauer Mihaela Lupse Frank Bloos Tom van der Poll W Joost Wiersinga Thierry Calandra Sylvain Meylan Alexander P J Vlaar Sebastian Weis Marleen A Slim Niels van Mourik Marcella C A Müller Antigone Kotsaki Lonneke van Vught Aline de Nooijer Lieke Bakkerus Nikolaos Antonakos ImmunoSep (Personalised Immunotherapy in Sepsis) international double-blind, double-dummy, placebo-controlled randomised clinical trial: study protocol BMJ Open |
| title | ImmunoSep (Personalised Immunotherapy in Sepsis) international double-blind, double-dummy, placebo-controlled randomised clinical trial: study protocol |
| title_full | ImmunoSep (Personalised Immunotherapy in Sepsis) international double-blind, double-dummy, placebo-controlled randomised clinical trial: study protocol |
| title_fullStr | ImmunoSep (Personalised Immunotherapy in Sepsis) international double-blind, double-dummy, placebo-controlled randomised clinical trial: study protocol |
| title_full_unstemmed | ImmunoSep (Personalised Immunotherapy in Sepsis) international double-blind, double-dummy, placebo-controlled randomised clinical trial: study protocol |
| title_short | ImmunoSep (Personalised Immunotherapy in Sepsis) international double-blind, double-dummy, placebo-controlled randomised clinical trial: study protocol |
| title_sort | immunosep personalised immunotherapy in sepsis international double blind double dummy placebo controlled randomised clinical trial study protocol |
| url | https://bmjopen.bmj.com/content/12/12/e067251.full |
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