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Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial

2021; Elsevier BV; Volume: 10; Issue: 3 Linguagem: Inglês

10.1016/s2213-2600(21)00494-x

2213-2619

Zelalem Temesgen, Charles D. Burger, Jason Baker, Christopher Polk, Claudia R. Libertin, Colleen F. Kelley, Vincent C. Marconi, Robert Orenstein, Victoria M. Catterson, William S. Aronstein, Cameron Durrant, Dale Chappell, Omar Ahmed, Gabrielle Chappell, Andrew D. Badley, Meghan Lewis, Linda Sher, Michael E. Bowdish, Noah Wald‐Dickler, Subarna Biswas, L.C.W. Lam, Khang Chung Ngoc Vo, R Poblete, May M. Lee, Douglass Hutcheon, Roberto L. Patron, John Gharbin, Caitlin A. Moran, Sheetal Kandiah, Valeria D. Cantos, Paulina A. Rebolledo, Carlos del Río, Jeffrey L. Lennox, Carmen Polito, Anandi N. Sheth, Anup Patel, Homero Paniagua, Seife Yohannes, Alpesh Amin, Richard Lee, Miki Watanabe, Lanny Hsieh, Martin Cearras, Amay Parikh, Jason Sniffen, Wilfred Onyia, Michael S Boger, Lisa Davidson, Kiran Gajurel, Michael Leonard, Lewis McCurdy, Nestor Quezada, Mindy Sampson, Zainab Shahid, Stephanie Strollo, David Weinrib, Sara Zulfigar, Cheryl McDonald, John Hollingsworth, John R. Burk, Joshua Berg, D Barbaro, Andrew C. Miller, Lakshmi Sambathkumar, Stuart McDonald, Obinna Okoye, Juan D Pulido, Jennifer C. Fulton, William B. Gill, Richard A. Zuckerman, Lionel D. Lewis, Chaitanya Mandapakala, Matthew K. Robinson, Brian S Metzger, Maqsood Alam, Chrisoula Politis, Anne Frosch, Linh Ngo, Fernando Carvalho Neuenschwander, Estêvão Lanna Figueiredo, Gualter CanÇado, Gustavo Gomes de Araújo, Lucas Melo Guimarães, Ricardo Sobhie Diaz, Natalia Bacellar, Celso H. L. Silva, Paulo Roberto Abrão Ferreira, Marina Andrade Lima, Caroline Uber Ghisi, Camila Anton, Ricardo Albaneze, Daniel Wagner de Castro Lima Santos, Ana Caroline Coutinho Iglessias, Marianna M. Lago, Paula Pietrobom, Maysa B. Alves, Juvencio Furtado, Leopoldo Tosi Trevelin, Valéria Telles, Francini Guerra Correa, Fabiano Ramos, Marina de A. R. Da Silva, Rebeca C. Lacerda Garcia, Ana Elizabeth G. Maldonado, Ana Carolina M. Beheregaray, Ana Maria T. Ortiz, Kléber Giovanni Luz, Eveline Pı́polo Milan, Janine Soares de Castro, Matheus José Barbosa Moreira, Renata Bezerra Onofre, TÁcito do Nascimento JÁcome, Victor Barreto Garcia, Victor Matheus Rolim de Souzafrom, Felipe Dal‐Pizzol, Cristiane Ritter, Marcelo B. Vinhas, Adilson Joaquim Westheimer Cavalcante, Julia Lutgens Minghini, Loni Dorigo, Marina Salgado Miranda, Martti Antila, Rebeca Mussi Brugnolli, Henrikki Antila,

Long-Term Effects of COVID-19

The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments.In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04351152, and is completed.Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41-137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79-89) participants in the lenzilumab group and in 190 (78%; 72-83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02-2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death.Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19, with a safety profile similar to that of placebo. The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown.Humanigen.