Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial)
Introduction In patients with septic shock, low levels of circulating immunoglobulins are common and their kinetics appear to be related to clinical outcome. The pivotal role of immunoglobulins in the host immune response to infection suggests that additional therapy with polyclonal intravenous immu...
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BMJ Publishing Group
2021-02-01
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| author | Giacomo Grasselli Patrizia Murino Emanuela Biagioni Martina Tosi Giorgio Berlot Giacomo Castiglione Alberto Corona Maria Giovanna De Cristofaro Abele Donati Paolo Feltracco Francesco Forfori Fiorentino Fragranza Ornella Piazza Livio Tullo |
| author_facet | Giacomo Grasselli Patrizia Murino Emanuela Biagioni Martina Tosi Giorgio Berlot Giacomo Castiglione Alberto Corona Maria Giovanna De Cristofaro Abele Donati Paolo Feltracco Francesco Forfori Fiorentino Fragranza Ornella Piazza Livio Tullo |
| author_sort | Giacomo Grasselli |
| collection | DOAJ |
| description | Introduction In patients with septic shock, low levels of circulating immunoglobulins are common and their kinetics appear to be related to clinical outcome. The pivotal role of immunoglobulins in the host immune response to infection suggests that additional therapy with polyclonal intravenous immunoglobulins may be a promising option in patients with septic shock. Immunoglobulin preparations enriched with the IgM component have largely been used in sepsis, mostly at standard dosages (250 mg/kg per day), regardless of clinical severity and without any dose adjustment based on immunoglobulin serum titres or other biomarkers. We hypothesised that a personalised dose of IgM enriched preparation based on patient IgM titres and aimed to achieve a specific threshold of IgM titre is more effective in decreasing mortality than a standard dose.Methods and analysis The study is designed as a multicentre, interventional, randomised, single-blinded, prospective, investigator sponsored, two-armed study. Patients with septic shock and IgM titres <60 mg/dL will be randomly assigned to an IgM titre-based treatment or a standard treatment group in a ratio of 1:1. The study will involve 12 Italian intensive care units and 356 patients will be enrolled. Patients assigned to the IgM titre-based treatment will receive a personalised daily dose based on an IgM serum titre aimed at achieving serum titres above 100 mg/dL up to discontinuation of vasoactive drugs or day 7 after enrolment. Patients assigned to the IgM standard treatment group will receive IgM enriched preparation daily for three consecutive days at the standard dose of 250 mg/kg. The primary endpoint will be all-cause mortality at 28 days.Ethics and dissemination The study protocol was approved by the ethics committees of the coordinating centre (Comitato Etico dell’Area Vasta Emilia Nord) and collaborating centres. The results of the trial will be published within 12 months from the end of the study and the steering committee has the right to present them at public symposia and conferences.Trial registration details The trial protocol and information documents have received a favourable opinion from the Area Vasta Emilia Nord Ethical Committee on 12 September 2019. The trial protocol has been registered on EudraCT (2018-001613-33) on 18 April 2018 and on ClinicalTrials.gov (NCT04182737) on 2 December 2019. |
| format | Article |
| id | doaj-art-7267ce17c61b4464a004623cee2f962e |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2021-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-7267ce17c61b4464a004623cee2f962e2024-11-17T07:35:12ZengBMJ Publishing GroupBMJ Open2044-60552021-02-0111210.1136/bmjopen-2019-036616Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial)Giacomo Grasselli0Patrizia Murino1Emanuela Biagioni2Martina Tosi3Giorgio Berlot4Giacomo Castiglione5Alberto Corona6Maria Giovanna De Cristofaro7Abele Donati8Paolo Feltracco9Francesco Forfori10Fiorentino Fragranza11Ornella Piazza12Livio Tullo13Anesthesia and Intensive Care Unit, La Fondazione IRCCS Ca Granda Ospedale Maggiore di Milano Policlinico, Milano, Lombardia, Italy3 Critical Area Department, Azienda Ospedaliera dei Colli-Cotugno and Monaldi Hospital, Napoli, ItalyAnesthesia and Intensive Care Unit, Azienda Ospedaliera-Universitaria Policlinico di Modena, Modena, ItalyAnesthesia and Intensive Care, University Hospital Modena, Modena, Emilia-Romagna, ItalyAnesthesia and Intensive Care Unit, Major Hospital of Trieste, Trieste, Friuli-Venezia Giulia, ItalyAnesthesia and Intensive Care Unit, University Hospital Vittorio Emanuele Catania Polyclinic, Catania, Sicilia, ItalyAnesthesia and Intensive Care Unit, Luigi Sacco University Hospital, Milano, Lombardia, ItalyAnesthesia and Intensive Care Unit, Antonio Cardarelli Hospital, Napoli, Campania, ItalyAnesthesia and Intensive Care Unit, Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona Umberto I G M Lancisi G Salesi, Ancona, Marche, ItalyAnesthesia and Intensive Care Unit, Azienda Ospedaliera di Padova, Padova, Veneto, ItalyAnesthesia and Intensive Care Unit, Pisa University Hospital, Pisa, Toscana, ItalyAnesthesia and Intensive Care Unit, Cotugno Hospital, Napoli, Campania, ItalyUniversità degli Studi di Salerno, Dipartimento di Medicina, Chirurgia, Odontoiatria Scuola Medica Salernitana, Baronissi, Baronissi (SA), ItalyAnesthesia and Intensive Care Unit, Foggia University Hospital, Foggia, Puglia, ItalyIntroduction In patients with septic shock, low levels of circulating immunoglobulins are common and their kinetics appear to be related to clinical outcome. The pivotal role of immunoglobulins in the host immune response to infection suggests that additional therapy with polyclonal intravenous immunoglobulins may be a promising option in patients with septic shock. Immunoglobulin preparations enriched with the IgM component have largely been used in sepsis, mostly at standard dosages (250 mg/kg per day), regardless of clinical severity and without any dose adjustment based on immunoglobulin serum titres or other biomarkers. We hypothesised that a personalised dose of IgM enriched preparation based on patient IgM titres and aimed to achieve a specific threshold of IgM titre is more effective in decreasing mortality than a standard dose.Methods and analysis The study is designed as a multicentre, interventional, randomised, single-blinded, prospective, investigator sponsored, two-armed study. Patients with septic shock and IgM titres <60 mg/dL will be randomly assigned to an IgM titre-based treatment or a standard treatment group in a ratio of 1:1. The study will involve 12 Italian intensive care units and 356 patients will be enrolled. Patients assigned to the IgM titre-based treatment will receive a personalised daily dose based on an IgM serum titre aimed at achieving serum titres above 100 mg/dL up to discontinuation of vasoactive drugs or day 7 after enrolment. Patients assigned to the IgM standard treatment group will receive IgM enriched preparation daily for three consecutive days at the standard dose of 250 mg/kg. The primary endpoint will be all-cause mortality at 28 days.Ethics and dissemination The study protocol was approved by the ethics committees of the coordinating centre (Comitato Etico dell’Area Vasta Emilia Nord) and collaborating centres. The results of the trial will be published within 12 months from the end of the study and the steering committee has the right to present them at public symposia and conferences.Trial registration details The trial protocol and information documents have received a favourable opinion from the Area Vasta Emilia Nord Ethical Committee on 12 September 2019. The trial protocol has been registered on EudraCT (2018-001613-33) on 18 April 2018 and on ClinicalTrials.gov (NCT04182737) on 2 December 2019.https://bmjopen.bmj.com/content/11/2/e036616.full |
| spellingShingle | Giacomo Grasselli Patrizia Murino Emanuela Biagioni Martina Tosi Giorgio Berlot Giacomo Castiglione Alberto Corona Maria Giovanna De Cristofaro Abele Donati Paolo Feltracco Francesco Forfori Fiorentino Fragranza Ornella Piazza Livio Tullo Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial) BMJ Open |
| title | Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial) |
| title_full | Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial) |
| title_fullStr | Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial) |
| title_full_unstemmed | Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial) |
| title_short | Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial) |
| title_sort | adjunctive igm enriched immunoglobulin therapy with a personalised dose based on serum igm titres versus standard dose in the treatment of septic shock a randomised controlled trial igm fat trial |
| url | https://bmjopen.bmj.com/content/11/2/e036616.full |
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