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 (PaO2/FiO2 below 350 mmHg) were randomized (2:1 ratio)...
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Autor*in:	Elisabeth De Leeuw [verfasserIn] Karel F. A. Van Damme [verfasserIn] Jozefien Declercq [verfasserIn] Cedric Bosteels [verfasserIn] Bastiaan Maes [verfasserIn] Simon J. Tavernier [verfasserIn] Laurent Detalle [verfasserIn] Trevor Smart [verfasserIn] Sophie Glatt [verfasserIn] Nincy Debeuf [verfasserIn] Julie Deckers [verfasserIn] Sahine Lameire [verfasserIn] Stefaan J. Vandecasteele [verfasserIn] Nikolaas De Neve [verfasserIn] Ingel K. Demedts [verfasserIn] Elke Govaerts [verfasserIn] Christiane Knoop [verfasserIn] Karolien Vanhove [verfasserIn] Michel Moutschen [verfasserIn] Wim Terryn [verfasserIn] Pieter Depuydt [verfasserIn] Eva Van Braeckel [verfasserIn] Filomeen Haerynck [verfasserIn] Tine C. J. Hendrickx [verfasserIn] Vanessa Parrein [verfasserIn] Marianna Lalla [verfasserIn] Claire Brittain [verfasserIn] Bart N. Lambrecht [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	COVID-19 Complement system Complement 5 Systemic inflammation

Übergeordnetes Werk:	In: Respiratory Research - BMC, 2003, 23(2022), 1, Seite 11
Übergeordnetes Werk:	volume:23 ; year:2022 ; number:1 ; pages:11

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12931-022-02126-2

Katalog-ID:	DOAJ026806207

Internformat


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245	1	0	\|a Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial
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520			\|a 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 < 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 (PaO2/FiO2) 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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700	0		\|a Karel F. A. Van Damme \|e verfasserin \|4 aut
700	0		\|a Jozefien Declercq \|e verfasserin \|4 aut
700	0		\|a Cedric Bosteels \|e verfasserin \|4 aut
700	0		\|a Bastiaan Maes \|e verfasserin \|4 aut
700	0		\|a Simon J. Tavernier \|e verfasserin \|4 aut
700	0		\|a Laurent Detalle \|e verfasserin \|4 aut
700	0		\|a Trevor Smart \|e verfasserin \|4 aut
700	0		\|a Sophie Glatt \|e verfasserin \|4 aut
700	0		\|a Nincy Debeuf \|e verfasserin \|4 aut
700	0		\|a Julie Deckers \|e verfasserin \|4 aut
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700	0		\|a Stefaan J. Vandecasteele \|e verfasserin \|4 aut
700	0		\|a Nikolaas De Neve \|e verfasserin \|4 aut
700	0		\|a Ingel K. Demedts \|e verfasserin \|4 aut
700	0		\|a Elke Govaerts \|e verfasserin \|4 aut
700	0		\|a Christiane Knoop \|e verfasserin \|4 aut
700	0		\|a Karolien Vanhove \|e verfasserin \|4 aut
700	0		\|a Michel Moutschen \|e verfasserin \|4 aut
700	0		\|a Wim Terryn \|e verfasserin \|4 aut
700	0		\|a Pieter Depuydt \|e verfasserin \|4 aut
700	0		\|a Eva Van Braeckel \|e verfasserin \|4 aut
700	0		\|a Filomeen Haerynck \|e verfasserin \|4 aut
700	0		\|a Tine C. J. Hendrickx \|e verfasserin \|4 aut
700	0		\|a Vanessa Parrein \|e verfasserin \|4 aut
700	0		\|a Marianna Lalla \|e verfasserin \|4 aut
700	0		\|a Claire Brittain \|e verfasserin \|4 aut
700	0		\|a Bart N. Lambrecht \|e verfasserin \|4 aut
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author_variant	e d l edl k f a v d kfavd j d jd c b cb b m bm s j t sjt l d ld t s ts s g sg n d nd j d jd s l sl s j v sjv n d n ndn i k d ikd e g eg c k ck k v kv m m mm w t wt p d pd e v b evb f h fh t c j h tcjh v p vp m l ml c b cb b n l bnl
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allfields	10.1186/s12931-022-02126-2 doi (DE-627)DOAJ026806207 (DE-599)DOAJd9849f76afef44ef98c3e2da010f83fc DE-627 ger DE-627 rakwb eng RC705-779 Elisabeth De Leeuw verfasserin aut Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 < 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 (PaO2/FiO2) 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. COVID-19 Complement system Complement 5 Systemic inflammation Diseases of the respiratory system Karel F. A. Van Damme verfasserin aut Jozefien Declercq verfasserin aut Cedric Bosteels verfasserin aut Bastiaan Maes verfasserin aut Simon J. Tavernier verfasserin aut Laurent Detalle verfasserin aut Trevor Smart verfasserin aut Sophie Glatt verfasserin aut Nincy Debeuf verfasserin aut Julie Deckers verfasserin aut Sahine Lameire verfasserin aut Stefaan J. Vandecasteele verfasserin aut Nikolaas De Neve verfasserin aut Ingel K. Demedts verfasserin aut Elke Govaerts verfasserin aut Christiane Knoop verfasserin aut Karolien Vanhove verfasserin aut Michel Moutschen verfasserin aut Wim Terryn verfasserin aut Pieter Depuydt verfasserin aut Eva Van Braeckel verfasserin aut Filomeen Haerynck verfasserin aut Tine C. J. Hendrickx verfasserin aut Vanessa Parrein verfasserin aut Marianna Lalla verfasserin aut Claire Brittain verfasserin aut Bart N. Lambrecht verfasserin aut In Respiratory Research BMC, 2003 23(2022), 1, Seite 11 (DE-627)326646485 (DE-600)2041675-1 1465993X nnns volume:23 year:2022 number:1 pages:11 https://doi.org/10.1186/s12931-022-02126-2 kostenfrei https://doaj.org/article/d9849f76afef44ef98c3e2da010f83fc kostenfrei https://doi.org/10.1186/s12931-022-02126-2 kostenfrei https://doaj.org/toc/1465-993X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 11
spelling	10.1186/s12931-022-02126-2 doi (DE-627)DOAJ026806207 (DE-599)DOAJd9849f76afef44ef98c3e2da010f83fc DE-627 ger DE-627 rakwb eng RC705-779 Elisabeth De Leeuw verfasserin aut Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 < 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 (PaO2/FiO2) 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. COVID-19 Complement system Complement 5 Systemic inflammation Diseases of the respiratory system Karel F. A. Van Damme verfasserin aut Jozefien Declercq verfasserin aut Cedric Bosteels verfasserin aut Bastiaan Maes verfasserin aut Simon J. Tavernier verfasserin aut Laurent Detalle verfasserin aut Trevor Smart verfasserin aut Sophie Glatt verfasserin aut Nincy Debeuf verfasserin aut Julie Deckers verfasserin aut Sahine Lameire verfasserin aut Stefaan J. Vandecasteele verfasserin aut Nikolaas De Neve verfasserin aut Ingel K. Demedts verfasserin aut Elke Govaerts verfasserin aut Christiane Knoop verfasserin aut Karolien Vanhove verfasserin aut Michel Moutschen verfasserin aut Wim Terryn verfasserin aut Pieter Depuydt verfasserin aut Eva Van Braeckel verfasserin aut Filomeen Haerynck verfasserin aut Tine C. J. Hendrickx verfasserin aut Vanessa Parrein verfasserin aut Marianna Lalla verfasserin aut Claire Brittain verfasserin aut Bart N. Lambrecht verfasserin aut In Respiratory Research BMC, 2003 23(2022), 1, Seite 11 (DE-627)326646485 (DE-600)2041675-1 1465993X nnns volume:23 year:2022 number:1 pages:11 https://doi.org/10.1186/s12931-022-02126-2 kostenfrei https://doaj.org/article/d9849f76afef44ef98c3e2da010f83fc kostenfrei https://doi.org/10.1186/s12931-022-02126-2 kostenfrei https://doaj.org/toc/1465-993X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 11
allfields_unstemmed	10.1186/s12931-022-02126-2 doi (DE-627)DOAJ026806207 (DE-599)DOAJd9849f76afef44ef98c3e2da010f83fc DE-627 ger DE-627 rakwb eng RC705-779 Elisabeth De Leeuw verfasserin aut Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 < 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 (PaO2/FiO2) 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. COVID-19 Complement system Complement 5 Systemic inflammation Diseases of the respiratory system Karel F. A. Van Damme verfasserin aut Jozefien Declercq verfasserin aut Cedric Bosteels verfasserin aut Bastiaan Maes verfasserin aut Simon J. Tavernier verfasserin aut Laurent Detalle verfasserin aut Trevor Smart verfasserin aut Sophie Glatt verfasserin aut Nincy Debeuf verfasserin aut Julie Deckers verfasserin aut Sahine Lameire verfasserin aut Stefaan J. Vandecasteele verfasserin aut Nikolaas De Neve verfasserin aut Ingel K. Demedts verfasserin aut Elke Govaerts verfasserin aut Christiane Knoop verfasserin aut Karolien Vanhove verfasserin aut Michel Moutschen verfasserin aut Wim Terryn verfasserin aut Pieter Depuydt verfasserin aut Eva Van Braeckel verfasserin aut Filomeen Haerynck verfasserin aut Tine C. J. Hendrickx verfasserin aut Vanessa Parrein verfasserin aut Marianna Lalla verfasserin aut Claire Brittain verfasserin aut Bart N. Lambrecht verfasserin aut In Respiratory Research BMC, 2003 23(2022), 1, Seite 11 (DE-627)326646485 (DE-600)2041675-1 1465993X nnns volume:23 year:2022 number:1 pages:11 https://doi.org/10.1186/s12931-022-02126-2 kostenfrei https://doaj.org/article/d9849f76afef44ef98c3e2da010f83fc kostenfrei https://doi.org/10.1186/s12931-022-02126-2 kostenfrei https://doaj.org/toc/1465-993X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 11
allfieldsGer	10.1186/s12931-022-02126-2 doi (DE-627)DOAJ026806207 (DE-599)DOAJd9849f76afef44ef98c3e2da010f83fc DE-627 ger DE-627 rakwb eng RC705-779 Elisabeth De Leeuw verfasserin aut Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 < 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 (PaO2/FiO2) 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. COVID-19 Complement system Complement 5 Systemic inflammation Diseases of the respiratory system Karel F. A. Van Damme verfasserin aut Jozefien Declercq verfasserin aut Cedric Bosteels verfasserin aut Bastiaan Maes verfasserin aut Simon J. Tavernier verfasserin aut Laurent Detalle verfasserin aut Trevor Smart verfasserin aut Sophie Glatt verfasserin aut Nincy Debeuf verfasserin aut Julie Deckers verfasserin aut Sahine Lameire verfasserin aut Stefaan J. Vandecasteele verfasserin aut Nikolaas De Neve verfasserin aut Ingel K. Demedts verfasserin aut Elke Govaerts verfasserin aut Christiane Knoop verfasserin aut Karolien Vanhove verfasserin aut Michel Moutschen verfasserin aut Wim Terryn verfasserin aut Pieter Depuydt verfasserin aut Eva Van Braeckel verfasserin aut Filomeen Haerynck verfasserin aut Tine C. J. Hendrickx verfasserin aut Vanessa Parrein verfasserin aut Marianna Lalla verfasserin aut Claire Brittain verfasserin aut Bart N. Lambrecht verfasserin aut In Respiratory Research BMC, 2003 23(2022), 1, Seite 11 (DE-627)326646485 (DE-600)2041675-1 1465993X nnns volume:23 year:2022 number:1 pages:11 https://doi.org/10.1186/s12931-022-02126-2 kostenfrei https://doaj.org/article/d9849f76afef44ef98c3e2da010f83fc kostenfrei https://doi.org/10.1186/s12931-022-02126-2 kostenfrei https://doaj.org/toc/1465-993X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 11
allfieldsSound	10.1186/s12931-022-02126-2 doi (DE-627)DOAJ026806207 (DE-599)DOAJd9849f76afef44ef98c3e2da010f83fc DE-627 ger DE-627 rakwb eng RC705-779 Elisabeth De Leeuw verfasserin aut Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 < 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 (PaO2/FiO2) 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. COVID-19 Complement system Complement 5 Systemic inflammation Diseases of the respiratory system Karel F. A. Van Damme verfasserin aut Jozefien Declercq verfasserin aut Cedric Bosteels verfasserin aut Bastiaan Maes verfasserin aut Simon J. Tavernier verfasserin aut Laurent Detalle verfasserin aut Trevor Smart verfasserin aut Sophie Glatt verfasserin aut Nincy Debeuf verfasserin aut Julie Deckers verfasserin aut Sahine Lameire verfasserin aut Stefaan J. Vandecasteele verfasserin aut Nikolaas De Neve verfasserin aut Ingel K. Demedts verfasserin aut Elke Govaerts verfasserin aut Christiane Knoop verfasserin aut Karolien Vanhove verfasserin aut Michel Moutschen verfasserin aut Wim Terryn verfasserin aut Pieter Depuydt verfasserin aut Eva Van Braeckel verfasserin aut Filomeen Haerynck verfasserin aut Tine C. J. Hendrickx verfasserin aut Vanessa Parrein verfasserin aut Marianna Lalla verfasserin aut Claire Brittain verfasserin aut Bart N. Lambrecht verfasserin aut In Respiratory Research BMC, 2003 23(2022), 1, Seite 11 (DE-627)326646485 (DE-600)2041675-1 1465993X nnns volume:23 year:2022 number:1 pages:11 https://doi.org/10.1186/s12931-022-02126-2 kostenfrei https://doaj.org/article/d9849f76afef44ef98c3e2da010f83fc kostenfrei https://doi.org/10.1186/s12931-022-02126-2 kostenfrei https://doaj.org/toc/1465-993X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 11
language	English
source	In Respiratory Research 23(2022), 1, Seite 11 volume:23 year:2022 number:1 pages:11
sourceStr	In Respiratory Research 23(2022), 1, Seite 11 volume:23 year:2022 number:1 pages:11
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	COVID-19 Complement system Complement 5 Systemic inflammation Diseases of the respiratory system
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container_title	Respiratory Research
authorswithroles_txt_mv	Elisabeth De Leeuw @@aut@@ Karel F. A. Van Damme @@aut@@ Jozefien Declercq @@aut@@ Cedric Bosteels @@aut@@ Bastiaan Maes @@aut@@ Simon J. Tavernier @@aut@@ Laurent Detalle @@aut@@ Trevor Smart @@aut@@ Sophie Glatt @@aut@@ Nincy Debeuf @@aut@@ Julie Deckers @@aut@@ Sahine Lameire @@aut@@ Stefaan J. Vandecasteele @@aut@@ Nikolaas De Neve @@aut@@ Ingel K. Demedts @@aut@@ Elke Govaerts @@aut@@ Christiane Knoop @@aut@@ Karolien Vanhove @@aut@@ Michel Moutschen @@aut@@ Wim Terryn @@aut@@ Pieter Depuydt @@aut@@ Eva Van Braeckel @@aut@@ Filomeen Haerynck @@aut@@ Tine C. J. Hendrickx @@aut@@ Vanessa Parrein @@aut@@ Marianna Lalla @@aut@@ Claire Brittain @@aut@@ Bart N. Lambrecht @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
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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 < 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. 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callnumber-first	R - Medicine
author	Elisabeth De Leeuw
spellingShingle	Elisabeth De Leeuw misc RC705-779 misc COVID-19 misc Complement system misc Complement 5 misc Systemic inflammation misc Diseases of the respiratory system Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial
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topic_title	RC705-779 Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial COVID-19 Complement system Complement 5 Systemic inflammation
topic	misc RC705-779 misc COVID-19 misc Complement system misc Complement 5 misc Systemic inflammation misc Diseases of the respiratory system
topic_unstemmed	misc RC705-779 misc COVID-19 misc Complement system misc Complement 5 misc Systemic inflammation misc Diseases of the respiratory system
topic_browse	misc RC705-779 misc COVID-19 misc Complement system misc Complement 5 misc Systemic inflammation misc Diseases of the respiratory system
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title	Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial
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title_full	Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial
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author_browse	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
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title_sort	efficacy and safety of the investigational complement c5 inhibitor zilucoplan in patients hospitalized with covid-19: an open-label randomized controlled trial
callnumber	RC705-779
title_auth	Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial
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 < 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 (PaO2/FiO2) 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.
abstractGer	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 < 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 (PaO2/FiO2) 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.
abstract_unstemmed	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 < 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 (PaO2/FiO2) 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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title_short	Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial
url	https://doi.org/10.1186/s12931-022-02126-2 https://doaj.org/article/d9849f76afef44ef98c3e2da010f83fc https://doaj.org/toc/1465-993X
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author2	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
author2Str	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
ppnlink	326646485
callnumber-subject	RC - Internal Medicine
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hochschulschrift_bool	false
doi_str	10.1186/s12931-022-02126-2
callnumber-a	RC705-779
up_date	2024-07-03T23:02:33.859Z
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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 < 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. 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Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial

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