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Background: Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection.
Methods: CONCOR-1 is an open-label, multicenter, randomized trial. Inclusion criteria include: patients >16 years; admitted to hospital with COVID-19 infection; receiving supplemental oxygen for respiratory complications of COVID-19; and, availability of blood group compatible CCP. Exclusion criteria are: onset of respiratory symptoms more than 12 days prior to randomization; intubated or planned for intubation; and previous severe reactions to plasma. Consenting patients will be randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP will be collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at Day 30. Secondary outcomes include ventilator free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α =0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n= 600).
Discussion: This trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titers and neutralization assays for donor qualification.
Trial registration: Clinicaltrials.gov NCT04348656; registered 16 April 2020; https://clinicaltrials.gov/ct2/show/NCT04348656?term=NCT04348656&draw=2&rank=1
Keywords
convalescent plasma, SARS-CoV-2, coronavirus, COVID-19
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This is a list of supplementary files associated with this preprint. Click to download.
- AddlFile1CONCOR1CRF01Oct2020v4.0English.pdf
Paper CRF package Version 4.0, 01 Oct 2020
- AddlFile2CONCOR1SAP25November2020v1.0English.pdf
Statistical Analysis Plan Version 1.0, 25 Nov 2020
- AddlFile3CONCOR1IDSMCCharter.pdf
IDSMC Charter version 2.0, 03 Nov 2020
- AddlFile4CONCOR1ICFs.pdf
Clinical Trials Ontario Consent Form Template (English) Version 1.2, 13 Apr 2020 & Consent Form Template (French- for Quebec sites) Version 1.1, 12 Apr 2020
- AddlFile7SPIRITchecklistcomplete06Nov2020.pdf
completed SPIRIT checklist
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CURRENT STATUS: Under Review
Version 1
Posted 04 Mar, 2021
No community comments so far
Review #1 received
Received 01 Mar, 2021
Editorial decision: Minor revision
On 01 Mar, 2021
Reviewer #1 agreed
On 25 Feb, 2021
Reviewers invited
Invitations sent on 25 Feb, 2021
Reviews received
Received 25 Feb, 2021
Editor assigned
On 21 Feb, 2021
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On 21 Feb, 2021
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On 12 Jan, 2021
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This preprint is under consideration at Trials. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 04 Mar, 2021
No community comments so far
Review #1 received
Received 01 Mar, 2021
Editorial decision: Minor revision
On 01 Mar, 2021
Reviewer #1 agreed
On 25 Feb, 2021
Reviewers invited
Invitations sent on 25 Feb, 2021
Reviews received
Received 25 Feb, 2021
Editor assigned
On 21 Feb, 2021
Submission checks complete
On 21 Feb, 2021
First submitted
On 12 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection.
Methods: CONCOR-1 is an open-label, multicenter, randomized trial. Inclusion criteria include: patients >16 years; admitted to hospital with COVID-19 infection; receiving supplemental oxygen for respiratory complications of COVID-19; and, availability of blood group compatible CCP. Exclusion criteria are: onset of respiratory symptoms more than 12 days prior to randomization; intubated or planned for intubation; and previous severe reactions to plasma. Consenting patients will be randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP will be collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at Day 30. Secondary outcomes include ventilator free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α =0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n= 600).
Discussion: This trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titers and neutralization assays for donor qualification.
Trial registration: Clinicaltrials.gov NCT04348656; registered 16 April 2020; https://clinicaltrials.gov/ct2/show/NCT04348656?term=NCT04348656&draw=2&rank=1
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
- AddlFile1CONCOR1CRF01Oct2020v4.0English.pdf
Paper CRF package Version 4.0, 01 Oct 2020
- AddlFile2CONCOR1SAP25November2020v1.0English.pdf
Statistical Analysis Plan Version 1.0, 25 Nov 2020
- AddlFile3CONCOR1IDSMCCharter.pdf
IDSMC Charter version 2.0, 03 Nov 2020
- AddlFile4CONCOR1ICFs.pdf
Clinical Trials Ontario Consent Form Template (English) Version 1.2, 13 Apr 2020 & Consent Form Template (French- for Quebec sites) Version 1.1, 12 Apr 2020
- AddlFile7SPIRITchecklistcomplete06Nov2020.pdf
completed SPIRIT checklist
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