Abstract: Research JAMA Internal Medicine | Original Investigation Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients A Randomized Clinical Trial Mila B. Ortigoza, MD, PhD; Hyunah Yoon, MD; Keith S. Goldfeld, DrPH; Andrea B. Troxel, ScD; Johanna P. Daily, MD, MS; Yinxiang Wu, MA; Yi Li, MS; Danni Wu, MS; Gia F. Cobb, MA; Gillian Baptiste, MD; Mary O’Keeffe, MD; Marilou O. Corpuz, MD; Luis Ostrosky-Zeichner, MD; Amee Amin, MD; Ioannis M. Zacharioudakis, MD; Dushyantha T. Jayaweera, MD; Yanyun Wu, MD; Julie V. Philley, MD; Megan S. Devine, MD; Mahalia S. Desruisseaux, MD; Alessandro D. Santin, MD; Shweta Anjan, MD, MBBS; Reeba Mathew, MD; Bela Patel, MD; Masayuki Nigo, MD; Rabi Upadhyay, MD; Tania Kupferman, MD; Andrew N. Dentino, MD; Rahul Nanchal, MD, MS; Christian A. Merlo, MD, MPH; David N. Hager, MD, PhD; Kartik Chandran, PhD; Jonathan R. Lai, PhD; Johanna Rivera, PhD; Chowdhury R. Bikash, PhD; Gorka Lasso, PhD; Timothy P. Hilbert, MD; Monika Paroder, MD, PhD; Andrea A. Asencio, BA; Mengling Liu, PhD; Eva Petkova, PhD; Alexander Bragat, MBA; Reza Shaker, MD; David D. McPherson, MD; Ralph L. Sacco, MD, MS; Marla J. Keller, MD; Corita R. Grudzen, MD; Judith S. Hochman, MD; Liise-anne Pirofski, MD; and the CONTAIN COVID-19 Consortium for the CONTAIN COVID-19 Study Group Visual Abstract IMPORTANCE There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in Supplemental content 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%)..