Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients : A Randomized Clinical Trial
Importance: There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19.
Objective: To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen.
Design, Setting, and Participants: CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation.
Interventions: A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline).
Main Outcomes and Measures: The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8.
Results: Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1] = 72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1] = 76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1] = 93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1] = 97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (P = .57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (P = .06).
Conclusions and Relevance: In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use.
Trial Registration: ClinicalTrials.gov Identifier: NCT04364737.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:182 |
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| Enthalten in: |
JAMA internal medicine - 182(2022), 2 vom: 01. Feb., Seite 115-126 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ortigoza, Mila B [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Completed 17.02.2022 Date Revised 07.03.2023 published: Print ClinicalTrials.gov: NCT04364737 Citation Status MEDLINE |
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| doi: |
10.1001/jamainternmed.2021.6850 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM33438477X |
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| 245 | 1 | 0 | |a Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients |b A Randomized Clinical Trial |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 17.02.2022 | ||
| 500 | |a Date Revised 07.03.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT04364737 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Importance: There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19 | ||
| 520 | |a Objective: To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen | ||
| 520 | |a Design, Setting, and Participants: CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation | ||
| 520 | |a Interventions: A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline) | ||
| 520 | |a Main Outcomes and Measures: The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8 | ||
| 520 | |a Results: Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1] = 72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1] = 76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1] = 93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1] = 97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (P = .57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (P = .06) | ||
| 520 | |a Conclusions and Relevance: In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use | ||
| 520 | |a Trial Registration: ClinicalTrials.gov Identifier: NCT04364737 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
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| 700 | 1 | |a Moldolsky, Lee C |e investigator |4 oth | |
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| 700 | 1 | |a Mendez, Sarah |e investigator |4 oth | |
| 700 | 1 | |a Hughes, Patricia |e investigator |4 oth | |
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| 700 | 1 | |a Lord, Aaron S |e investigator |4 oth | |
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| 700 | 1 | |a Sheikh, Masooma |e investigator |4 oth | |
| 700 | 1 | |a Visconti-Ferrara, Erica |e investigator |4 oth | |
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| 700 | 1 | |a Youn, Heekoung |e investigator |4 oth | |
| 700 | 1 | |a Jane Fran, Baby |e investigator |4 oth | |
| 700 | 1 | |a Medina, Rosario |e investigator |4 oth | |
| 700 | 1 | |a McKell, Renee |e investigator |4 oth | |
| 700 | 1 | |a Khan, Saila |e investigator |4 oth | |
| 700 | 1 | |a Hamilton, Tanya |e investigator |4 oth | |
| 700 | 1 | |a Sanchez, Carlos J |e investigator |4 oth | |
| 700 | 1 | |a Patel, Nandini H |e investigator |4 oth | |
| 700 | 1 | |a Cleare, Levi |e investigator |4 oth | |
| 700 | 1 | |a Vergnolle, Olivia |e investigator |4 oth | |
| 700 | 1 | |a Nakouzi, Antonio |e investigator |4 oth | |
| 700 | 1 | |a Quevedo, Gregory |e investigator |4 oth | |
| 700 | 1 | |a Bortz, Robert H |c 3rd |e investigator |4 oth | |
| 700 | 1 | |a Wirchnianski, Ariel S |e investigator |4 oth | |
| 700 | 1 | |a Florez, Catalina |e investigator |4 oth | |
| 700 | 1 | |a Babb, Rachelle |e investigator |4 oth | |
| 700 | 1 | |a Ayala, Jennifer |e investigator |4 oth | |
| 700 | 1 | |a Tsagaris, K Zoe |e investigator |4 oth | |
| 700 | 1 | |a James, Andria |e investigator |4 oth | |
| 700 | 1 | |a Eke, Isaiah |e investigator |4 oth | |
| 700 | 1 | |a Obeidallah, Aisha |e investigator |4 oth | |
| 700 | 1 | |a Sandu, Oana A |e investigator |4 oth | |
| 700 | 1 | |a Sohval, Sophie |e investigator |4 oth | |
| 700 | 1 | |a Serrano-Rahman, Leana |e investigator |4 oth | |
| 700 | 1 | |a Uehlinger, Joan |e investigator |4 oth | |
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| 700 | 1 | |a Al-Abduladheem, Aya |e investigator |4 oth | |
| 700 | 1 | |a Gendlina, Inessa |e investigator |4 oth | |
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| 700 | 1 | |a Bortnick, Anna |e investigator |4 oth | |
| 700 | 1 | |a Eichler, Jeremy |e investigator |4 oth | |
| 700 | 1 | |a Kaufman, Rachel |e investigator |4 oth | |
| 700 | 1 | |a Yukelis, Sarah |e investigator |4 oth | |
| 700 | 1 | |a Pennock, Michael |e investigator |4 oth | |
| 700 | 1 | |a Goggin, Michelle |e investigator |4 oth | |
| 700 | 1 | |a Shen, Christine |e investigator |4 oth | |
| 700 | 1 | |a Annam, Jayabhargav |e investigator |4 oth | |
| 700 | 1 | |a Khokhar, Ahmed |e investigator |4 oth | |
| 700 | 1 | |a Barboto, Daniel |e investigator |4 oth | |
| 700 | 1 | |a Lally, Brianna J |e investigator |4 oth | |
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| 700 | 1 | |a Lee, Max |e investigator |4 oth | |
| 700 | 1 | |a Yang, Xiuyi A |e investigator |4 oth | |
| 700 | 1 | |a Allen, Stephanie |e investigator |4 oth | |
| 700 | 1 | |a Malaviya, Avinash |e investigator |4 oth | |
| 700 | 1 | |a Moussa, Omar |e investigator |4 oth | |
| 700 | 1 | |a Park, Rosa |e investigator |4 oth | |
| 700 | 1 | |a Sample, Reise |e investigator |4 oth | |
| 700 | 1 | |a Bae, Andrea |e investigator |4 oth | |
| 700 | 1 | |a Benoni, Galit |e investigator |4 oth | |
| 700 | 1 | |a Boerger, Lindsie L |e investigator |4 oth | |
| 700 | 1 | |a Baker, Lisa D |e investigator |4 oth | |
| 700 | 1 | |a Luther, Martha A |e investigator |4 oth | |
| 700 | 1 | |a Ameti, Lirim S |e investigator |4 oth | |
| 700 | 1 | |a Briggs, Neima |e investigator |4 oth | |
| 700 | 1 | |a Golden, Marjorie R |e investigator |4 oth | |
| 700 | 1 | |a Gormally, Michael |e investigator |4 oth | |
| 700 | 1 | |a Huang, Gloria S |e investigator |4 oth | |
| 700 | 1 | |a Johnson, Raymond M |e investigator |4 oth | |
| 700 | 1 | |a Morrison, Alyssa R |e investigator |4 oth | |
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| 700 | 1 | |a Cortezzo, Grace M |e investigator |4 oth | |
| 700 | 1 | |a Debski, Kay B |e investigator |4 oth | |
| 700 | 1 | |a Nicoletti |e investigator |4 oth | |
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| 700 | 1 | |a Bertran-Lopez, Jovanna |e investigator |4 oth | |
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