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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 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), 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 (NCT05271929), EudraCT (2021-006621-22)

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1136/bmjopen-2022-071277

Authors

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Role:
Author
ORCID:
0000-0002-3801-5297
More by this author
Role:
Author
ORCID:
0000-0003-3690-2498


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Funder identifier:
https://ror.org/04pz7b180
Grant:
16LW0108
Programme:
Projektträger VDE/VDI
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Funder identifier:
https://ror.org/00k4n6c32
Grant:
101015756
More from this funder
Funder identifier:
https://ror.org/01yaj9a77
Grant:
10430062010001


Publisher:
BMJ Publishing
Journal:
BMJ Open More from this journal
Volume:
13
Issue:
4
Article number:
e071277
Publication date:
2023-04-27
Acceptance date:
2023-02-24
DOI:
EISSN:
2044-6055
ISSN:
2044-6055
Pmid:
37105693

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