학술논문
Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial
Document Type
article
Author
Elisabeth De Leeuw; Karel F. A. Van Damme; Jozefien Declercq; Cedric Bosteels; Bastiaan Maes; Simon J. Tavernier; Laurent Detalle; Trevor Smart; Sophie Glatt; Nincy Debeuf; Julie Deckers; Sahine Lameire; Stefaan J. Vandecasteele; Nikolaas De Neve; Ingel K. Demedts; Elke Govaerts; Christiane Knoop; Karolien Vanhove; Michel Moutschen; Wim Terryn; Pieter Depuydt; Eva Van Braeckel; Filomeen Haerynck; Tine C. J. Hendrickx; Vanessa Parrein; Marianna Lalla; Claire Brittain; Bart N. Lambrecht
Source
Respiratory Research, Vol 23, Iss 1, Pp 1-11 (2022)
Subject
Language
English
ISSN
1465-993X
Abstract
Abstract Background The efficacy and safety of complement inhibition in COVID-19 patients is unclear. Methods A multicenter randomized controlled, open-label trial. Hospitalized COVID-19 patients with signs of systemic inflammation and hypoxemia (PaO2/FiO2 below 350 mmHg) were randomized (2:1 ratio) to receive standard of care with or without the C5 inhibitor zilucoplan daily for 14 days, under antibiotic prophylaxis. The primary outcome was improvement in oxygenation at day 6 and 15. Results 81 patients were randomly assigned to zilucoplan (n = 55) or the control group (n = 26). 78 patients were included in the safety and primary analysis. Most were men (87%) and the median age was 63 years. The mean improvement in PaO2/FiO2 from baseline to day 6 was 56.4 mmHg in the zilucoplan group and 20.6 mmHg in the control group (mean difference + 35.8; 95% confidence interval (CI) − 9.4 to 80.9; p = 0.12), an effect also observed at day 15. Day 28 mortality was 9% in the zilucoplan and 21% in the control group (odds ratio 0.4; 95% CI 0.1 to 1.5). At long-term follow up, the distance walked in a 6-min test was 539.7 m in zilucoplan and 490.6 m in the control group (p = 0.18). Zilucoplan lowered serum C5b-9 (p