Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial
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; 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
Importance/UNASSIGNED:There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04364737.
PMID: 34901997
ISSN: 2168-6114
CID: 5084962
Maintaining adequate donations and a sustainable blood supply: Lessons learned
Gammon, Richard R; Rosenbaum, Lizabeth; Cooke, Rhonda; Friedman, Mark; Rockwood, Linda; Nichols, Tracie; Vossoughi, Sarah
BACKGROUND:The availability of a safe blood supply is a key component of transfusion medicine. A decade of decreased blood use, decreased payment for products, and a dwindling donor base have placed the sustainability of the US blood supply at risk. STUDY DESIGN AND METHODS/METHODS:A literature review was performed for blood center (BC) and hospital disaster management, chronically transfusion-dependent diseases, and appropriate use of group O-negative red blood cells (RBCs), and the Choosing Wisely campaign. The aim was to identify current practice and to make recommendations for BC and hospital actions. RESULTS:While BCs are better prepared to handle disasters than after the 9/11 attacks, messaging to the public remains difficult, as donors often do not realize that blood transfused during a disaster was likely collected before the event. BCs and transfusion services should participate in drafting disaster response plans. Hospitals should maintain inventories adequate for patients in the event supply is disrupted. Providing specialty products for transfusion-dependent patients can strain collections, lead to increased use of group O RBCs, and create logistical inventory challenges for hospitals. The AABB Choosing Wisely initiative addresses overuse of blood components to optimally use this precious resource. Group O-negative RBCs should be transfused only to patients who truly need them. CONCLUSIONS:Collecting and maintaining a blood supply robust enough to handle disasters and transfusion-dependent patients in need of specialty products is challenging. Collaboration of all parties should help to optimize resources, ensure appropriate collections, improve patient care, and ultimately result in a robust, sustainable blood supply.
PMCID:7753343
PMID: 33206404
ISSN: 1537-2995
CID: 4734662