Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial.
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Ortigoza Mila B, Yoon Hyunah, Goldfeld Keith S, Troxel Andrea B, Daily Johanna P, Wu Yinxiang, Li Yi, Wu Danni, Cobb Gia F, Baptiste Gillian, O'Keeffe Mary, Corpuz Marilou O, Ostrosky-Zeichner Luis, Amin Amee, Zacharioudakis Ioannis M, Jayaweera Dushyantha T, Wu Yanyun, Philley Julie V, Devine Megan S, Desruisseaux Mahalia S, Santin Alessandro D, Anjan Shweta, Mathew Reeba, Patel Bela, Nigo Masayuki, Upadhyay Rabi, Kupferman Tania, Dentino Andrew N, Nanchal Rahul, Merlo Christian A, Hager David N, Chandran Kartik, Lai Jonathan R, Rivera Johanna, Bikash Chowdhury R, Lasso Gorka, Hilbert Timothy P, Paroder Monika, Asencio Andrea A, Liu Mengling, Petkova Eva, Bragat Alexander, Shaker Reza, McPherson David D, Sacco Ralph L, Keller Marla J, Grudzen Corita R, Hochman Judith S, Pirofski Liise-Anne, CONTAIN COVID-19 Consortium for the CONTAIN COVID-19 Study Group, Parameswaran Lalitha, Corcoran Anthony T, Rohatgi Abhinav, Wronska Marta W, Wu Xinyuan, Srinivasan Ranjini, Deng Fang-Ming, Filardo Thomas D, Pendse Jay, Blaser Simone B, Whyte Olga, Gallagher Jacqueline M, Thomas Ololade E, Ramos Danibel, Sturm-Reganato Caroline L, Fong Charlotte C, Daus Ivy M, Payoen Arianne Gisselle, Chiofolo Joseph T, Friedman Mark T, Wu Ding Wen, Jacobson Jessica L, Schneider Jeffrey G, Sarwar Uzma N, Wang Henry E, Huebinger Ryan M, Dronavalli Goutham, Bai Yu, Grimes Carolyn Z, Eldin Karen W, Umana Virginia E, Martin Jessica G, Heath Timothy R, Bello Fatimah O, Ransford Daru Lane, Laurent-Rolle Maudry, Shenoi Sheela V, Akide-Ndunge Oscar Bate, Thapa Bipin, Peterson Jennifer L, Knauf Kelly, Patel Shivani U, Cheney Laura L, Tormey Christopher A, Hendrickson Jeanne E
Аннотация
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.