A multicenter randomized trial to assess the efficacy of CONvalescent plasma therapy in patients with Invasive COVID-19 and acute respiratory failure treated with mechanical ventilation: the CONFIDENT trial protocol

BMC Pulmonary Medicine

Anne-Françoise Donneau¹  Tome Najdovski²  Veerle Compernolle³  Mutien Garigliany⁴  Daniel Desmecht⁴  André Gothot⁵  Michel Moutschen⁶  David Grimaldi⁷  Eric Hoste⁸  Benoît Misset⁹  Pierre-François Laterre^1,10  Geert Meyfroidt^1,11 

[1] Biostatistic Unit, Public Health Department, Liège University, Liège, Belgium;Blood Services From the Red Cross, Suarlée, Belgium;Blood Services from the Red Cross, Mechelen, Belgium;Department of Animal Pathology, Liège University, Liège, Belgium;Department of Immunohematology, Liege University Hospital, Liège, Belgium;Department of Infectious Diseases, Liege University Hospital, Liège, Belgium;Department of Intensive Care Medicine, Cliniques Universitaires de Bruxelles - Erasme, Université Libre de Bruxelles, Brussels, Belgium;Department of Intensive Care Medicine, Gent University Hospital, Gent, Belgium;Department of Intensive Care Medicine, Liege University Hospital, Domaine Universitaire du Sart Tilman, 4020, Liège, Belgium;Department of Intensive Care Medicine, Saint-Luc University Hospital, Brussels, Belgium;Department of Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium;

关键词: COVID-19;    Convalescent plasma;    Randomized;    Respiratory failure;    Mechanical ventilation;   

DOI  :  10.1186/s12890-020-01361-x

来源: Springer

【 摘 要 】

BackgroundThe COVID-19 pandemic reached Europe in early 2020. Convalescent plasma is used without a consistent evidence of efficacy. Our hypothesis is that passive immunization with plasma collected from patients having contracted COVID-19 and developed specific neutralizing antibodies may alleviate symptoms and reduce mortality in patients treated with mechanical ventilation for severe respiratory failure during the evolution of SARS-CoV-2 pneumonia.MethodsWe plan to include 500 adult patients, hospitalized in 16 Belgian intensive care units between September 2020 and 2022, diagnosed with SARS-CoV-2 pneumonia, under mechanical ventilation for less than 5 days and a clinical frailty scale less than 6. The study treatment will be compared to standard of care and allocated by randomization in a 1 to 1 ratio without blinding. The main endpoint will be mortality at day 28. We will perform an intention to treat analysis. The number of patients to include is based on an expected mortality rate at day 28 of 40 percent and an expected relative reduction with study intervention of 30 percent with α risk of 5 percent and β risk of 20 percent.DiscussionThis study will assess the efficacy of plasma in the population of mechanically ventilated patients. A stratification on the delay from mechanical ventilation and inclusion will allow to approach the optimal time use. Selecting convalescent plasmas with a high titer of neutralizing antibodies against SARS-CoV-2 will allow a homogeneous study treatment. The inclusion in the study is based on the consent of the patient or his/her legal representative, and the approval of the Investigational Review Board of the University hospital of Liège, Belgium. A data safety monitoring board (DSMB) has been implemented. Interim analyses have been planned at 100, 2002, 300 and 400 inclusions in order to decide whether the trail should be discontinued prematurely for ethical issues. We plan to publish our results in a peer-reviewed journal and to present them at national and international conferences.Funding and registrationThe trial is funded by the Belgian Health Care Knowledge Center KCE # COV201004Trial registrationClinicaltrials.gov registration number NCT04558476. Registered 14 September 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04558476

【 授权许可】

CC BY