Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19 (COVIC-19): protocol for a randomised, open-label trial

Maxime Desmarets; Simone Hoffmann; Charline Vauchy; Bart J.A. Rijnders; Eric Toussirot; Antoine Durrbach; Sixten Körper; Eva Schrezenmeier; C. Ellen Van Der Schoot; Heli Harvala; Gaëlle Brunotte; Thomas Appl; Erhard Seifried; Pierre Tiberghien; Daniel Bradshaw; David J. Roberts; Lise J. Estcourt; Hubert Schrezenmeier

doi:10.1136/bmjopen-2022-071277

Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19 (COVIC-19): protocol for a randomised, open-label trial

Maxime Desmarets^*, Simone Hoffmann, Charline Vauchy, Bart J.A. Rijnders, Eric Toussirot, Antoine Durrbach, Sixten Körper, Eva Schrezenmeier, C. Ellen Van Der Schoot, Heli Harvala, Gaëlle Brunotte, Thomas Appl, Erhard Seifried, Pierre Tiberghien, Daniel Bradshaw, David J. Roberts, Lise J. Estcourt, Hubert Schrezenmeier

^*Corresponding author for this work

Internal Medicine

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Introduction COVID-19 convalescent plasma (CCP) is a possible treatment option for COVID-19. A comprehensive number of clinical trials on CCP efficacy have already been conducted. However, many aspects of CCP treatment still require investigations: in particular (1) Optimisation of the CCP product, (2) Identification of the patient population in need and most likely to benefit from this treatment approach, (3) Timing of administration and (4) CCP efficacy across viral variants in vivo. We aimed to test whether high-titre CCP, administered early, is efficacious in preventing hospitalisation or death in high-risk patients. Methods and analysis COVIC-19 is a multicentre, randomised, open-label, adaptive superiority phase III trial comparing CCP with very high neutralising antibody titre administered within 7 days of symptom onset plus standard of care versus standard of care alone. We will enrol patients in two cohorts of vulnerable patients [(1) elderly 70+ years, or younger with comorbidities; (2) immunocompromised patients]. Up to 1020 participants will be enrolled in each cohort (at least 340 with a sample size re-estimation after reaching 102 patients). The primary endpoint is the proportion of participants with (1) Hospitalisation due to progressive COVID-19, or (2) Who died by day 28 after randomisation. Principal analysis will follow the intention-to-treat principle. Ethics and dissemination Ethical approval has been granted by the University of Ulm ethics committee (#41/22) (lead ethics committee for Germany), Comité de protection des personnes Sud-Est I (CPP Sud-Est I) (#2022-A01307-36) (ethics committee for France), and ErasmusMC ethics committee (#MEC-2022-0365) (ethics committee for the Netherlands). Signed informed consent will be obtained from all included patients. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings. Trial registration Clinical Trials.gov

Original language	English
Article number	e071277
Journal	BMJ Open
Volume	13
Issue number	4
DOIs	https://doi.org/10.1136/bmjopen-2022-071277
Publication status	Published - 27 Apr 2023

Bibliographical note

Funding Information:
This work is supported by the Support-e project, a project funded by the European Union’s Horizon 2020 research and innovation programme (grant number 101015756, www.support-e.eu ), the German Bundesministerium für Bildung und Forschung (BMBF, Projektträger VDE/VDI grant number 16LW0108), and ZonMw, the Netherlands Organisation for Health Research and Development (grant number 10430062010001). The funding sources had no role in the design of the study and will not have any role during its conduct, analysis, interpretation of findings or decision to submit results.

Publisher Copyright:
© 2023 BMJ Publishing Group. All rights reserved.

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Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19 (COVIC-19) protocol for a randomised, open-label trialFinal published version, 8.08 MBLicence: CC BY-NC

Cite this

Desmarets, M., Hoffmann, S., Vauchy, C., Rijnders, B. J. A., Toussirot, E., Durrbach, A., Körper, S., Schrezenmeier, E., Van Der Schoot, C. E., Harvala, H., Brunotte, G., Appl, T., Seifried, E., Tiberghien, P., Bradshaw, D., Roberts, D. J., Estcourt, L. J., & Schrezenmeier, H. (2023). Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19 (COVIC-19): protocol for a randomised, open-label trial. BMJ Open, 13(4), Article e071277. https://doi.org/10.1136/bmjopen-2022-071277

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title = "Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19 (COVIC-19): protocol for a randomised, open-label trial",

abstract = "Introduction COVID-19 convalescent plasma (CCP) is a possible treatment option for COVID-19. A comprehensive number of clinical trials on CCP efficacy have already been conducted. However, many aspects of CCP treatment still require investigations: in particular (1) Optimisation of the CCP product, (2) Identification of the patient population in need and most likely to benefit from this treatment approach, (3) Timing of administration and (4) CCP efficacy across viral variants in vivo. We aimed to test whether high-titre CCP, administered early, is efficacious in preventing hospitalisation or death in high-risk patients. Methods and analysis COVIC-19 is a multicentre, randomised, open-label, adaptive superiority phase III trial comparing CCP with very high neutralising antibody titre administered within 7 days of symptom onset plus standard of care versus standard of care alone. We will enrol patients in two cohorts of vulnerable patients [(1) elderly 70+ years, or younger with comorbidities; (2) immunocompromised patients]. Up to 1020 participants will be enrolled in each cohort (at least 340 with a sample size re-estimation after reaching 102 patients). The primary endpoint is the proportion of participants with (1) Hospitalisation due to progressive COVID-19, or (2) Who died by day 28 after randomisation. Principal analysis will follow the intention-to-treat principle. Ethics and dissemination Ethical approval has been granted by the University of Ulm ethics committee (\#41/22) (lead ethics committee for Germany), Comit{\'e} de protection des personnes Sud-Est I (CPP Sud-Est I) (\#2022-A01307-36) (ethics committee for France), and ErasmusMC ethics committee (\#MEC-2022-0365) (ethics committee for the Netherlands). Signed informed consent will be obtained from all included patients. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings. Trial registration Clinical Trials.gov",

author = "Maxime Desmarets and Simone Hoffmann and Charline Vauchy and Rijnders, \{Bart J.A.\} and Eric Toussirot and Antoine Durrbach and Sixten K{\"o}rper and Eva Schrezenmeier and \{Van Der Schoot\}, \{C. Ellen\} and Heli Harvala and Ga{\"e}lle Brunotte and Thomas Appl and Erhard Seifried and Pierre Tiberghien and Daniel Bradshaw and Roberts, \{David J.\} and Estcourt, \{Lise J.\} and Hubert Schrezenmeier",

note = "Funding Information: This work is supported by the Support-e project, a project funded by the European Union{\textquoteright}s Horizon 2020 research and innovation programme (grant number 101015756, www.support-e.eu ), the German Bundesministerium f{\"u}r Bildung und Forschung (BMBF, Projekttr{\"a}ger VDE/VDI grant number 16LW0108), and ZonMw, the Netherlands Organisation for Health Research and Development (grant number 10430062010001). The funding sources had no role in the design of the study and will not have any role during its conduct, analysis, interpretation of findings or decision to submit results. Publisher Copyright: {\textcopyright} 2023 BMJ Publishing Group. All rights reserved.",

year = "2023",

month = apr,

day = "27",

doi = "10.1136/bmjopen-2022-071277",

language = "English",

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Desmarets, M, Hoffmann, S, Vauchy, C, Rijnders, BJA, Toussirot, E, Durrbach, A, Körper, S, Schrezenmeier, E, Van Der Schoot, CE, Harvala, H, Brunotte, G, Appl, T, Seifried, E, Tiberghien, P, Bradshaw, D, Roberts, DJ, Estcourt, LJ & Schrezenmeier, H 2023, 'Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19 (COVIC-19): protocol for a randomised, open-label trial', BMJ Open, vol. 13, no. 4, e071277. https://doi.org/10.1136/bmjopen-2022-071277

TY - JOUR

T1 - Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19 (COVIC-19)

T2 - protocol for a randomised, open-label trial

AU - Desmarets, Maxime

AU - Hoffmann, Simone

AU - Vauchy, Charline

AU - Rijnders, Bart J.A.

AU - Toussirot, Eric

AU - Durrbach, Antoine

AU - Körper, Sixten

AU - Schrezenmeier, Eva

AU - Van Der Schoot, C. Ellen

AU - Harvala, Heli

AU - Brunotte, Gaëlle

AU - Appl, Thomas

AU - Seifried, Erhard

AU - Tiberghien, Pierre

AU - Bradshaw, Daniel

AU - Roberts, David J.

AU - Estcourt, Lise J.

AU - Schrezenmeier, Hubert

N1 - Funding Information: This work is supported by the Support-e project, a project funded by the European Union’s Horizon 2020 research and innovation programme (grant number 101015756, www.support-e.eu ), the German Bundesministerium für Bildung und Forschung (BMBF, Projektträger VDE/VDI grant number 16LW0108), and ZonMw, the Netherlands Organisation for Health Research and Development (grant number 10430062010001). The funding sources had no role in the design of the study and will not have any role during its conduct, analysis, interpretation of findings or decision to submit results. Publisher Copyright: © 2023 BMJ Publishing Group. All rights reserved.

PY - 2023/4/27

Y1 - 2023/4/27

N2 - Introduction COVID-19 convalescent plasma (CCP) is a possible treatment option for COVID-19. A comprehensive number of clinical trials on CCP efficacy have already been conducted. However, many aspects of CCP treatment still require investigations: in particular (1) Optimisation of the CCP product, (2) Identification of the patient population in need and most likely to benefit from this treatment approach, (3) Timing of administration and (4) CCP efficacy across viral variants in vivo. We aimed to test whether high-titre CCP, administered early, is efficacious in preventing hospitalisation or death in high-risk patients. Methods and analysis COVIC-19 is a multicentre, randomised, open-label, adaptive superiority phase III trial comparing CCP with very high neutralising antibody titre administered within 7 days of symptom onset plus standard of care versus standard of care alone. We will enrol patients in two cohorts of vulnerable patients [(1) elderly 70+ years, or younger with comorbidities; (2) immunocompromised patients]. Up to 1020 participants will be enrolled in each cohort (at least 340 with a sample size re-estimation after reaching 102 patients). The primary endpoint is the proportion of participants with (1) Hospitalisation due to progressive COVID-19, or (2) Who died by day 28 after randomisation. Principal analysis will follow the intention-to-treat principle. Ethics and dissemination Ethical approval has been granted by the University of Ulm ethics committee (#41/22) (lead ethics committee for Germany), Comité de protection des personnes Sud-Est I (CPP Sud-Est I) (#2022-A01307-36) (ethics committee for France), and ErasmusMC ethics committee (#MEC-2022-0365) (ethics committee for the Netherlands). Signed informed consent will be obtained from all included patients. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings. Trial registration Clinical Trials.gov

AB - Introduction COVID-19 convalescent plasma (CCP) is a possible treatment option for COVID-19. A comprehensive number of clinical trials on CCP efficacy have already been conducted. However, many aspects of CCP treatment still require investigations: in particular (1) Optimisation of the CCP product, (2) Identification of the patient population in need and most likely to benefit from this treatment approach, (3) Timing of administration and (4) CCP efficacy across viral variants in vivo. We aimed to test whether high-titre CCP, administered early, is efficacious in preventing hospitalisation or death in high-risk patients. Methods and analysis COVIC-19 is a multicentre, randomised, open-label, adaptive superiority phase III trial comparing CCP with very high neutralising antibody titre administered within 7 days of symptom onset plus standard of care versus standard of care alone. We will enrol patients in two cohorts of vulnerable patients [(1) elderly 70+ years, or younger with comorbidities; (2) immunocompromised patients]. Up to 1020 participants will be enrolled in each cohort (at least 340 with a sample size re-estimation after reaching 102 patients). The primary endpoint is the proportion of participants with (1) Hospitalisation due to progressive COVID-19, or (2) Who died by day 28 after randomisation. Principal analysis will follow the intention-to-treat principle. Ethics and dissemination Ethical approval has been granted by the University of Ulm ethics committee (#41/22) (lead ethics committee for Germany), Comité de protection des personnes Sud-Est I (CPP Sud-Est I) (#2022-A01307-36) (ethics committee for France), and ErasmusMC ethics committee (#MEC-2022-0365) (ethics committee for the Netherlands). Signed informed consent will be obtained from all included patients. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings. Trial registration Clinical Trials.gov

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U2 - 10.1136/bmjopen-2022-071277

DO - 10.1136/bmjopen-2022-071277

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AN - SCOPUS:85158851358

SN - 2044-6055

VL - 13

JO - BMJ Open

JF - BMJ Open

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M1 - e071277

ER -

Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19 (COVIC-19): protocol for a randomised, open-label trial

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