Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial
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 (PaO 2 /FiO 2 below 350 mmHg) were randomized (2:1 ra...
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Published in | Respiratory research Vol. 23; no. 1; pp. 1 - 11 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article Web Resource |
Language | English |
Published |
London
BioMed Central Ltd
09.08.2022
BioMed Central BMC |
Subjects | |
Online Access | Get full text |
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Summary: | 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 (PaO
2
/FiO
2
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 PaO
2
/FiO
2
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 < 0.001) and interleukin-8 (p = 0.03) concentration compared with control. No relevant safety differences between the zilucoplan and control group were identified.
Conclusion
Administration of zilucoplan to COVID-19 patients in this proof-of-concept randomized trial was well tolerated under antibiotic prophylaxis. While not reaching statistical significance, indicators of respiratory function (PaO
2
/FiO
2
) and clinical outcome (mortality and 6-min walk test) suggest that C5 inhibition might be beneficial, although this requires further research in larger randomized studies
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 scopus-id:2-s2.0-85135701952 |
ISSN: | 1465-993X 1465-9921 1465-993X 1465-9921 |
DOI: | 10.1186/s12931-022-02126-2 |