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Randomized Controlled Trial
. 2021 Nov 1;4(11):e2136246.
doi: 10.1001/jamanetworkopen.2021.36246.

Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients With COVID-19 Pneumonia: A Randomized Clinical Trial

Francesco Menichetti  1 , Patrizia Popoli  2 , Maria Puopolo  3 , Stefania Spila Alegiani  2 , Giusy Tiseo  1 , Alessandro Bartoloni  4 , Giuseppe Vittorio De Socio  5 , Sauro Luchi  6 , Pierluigi Blanc  7 , Massimo Puoti  8   9 , Elena Toschi  10 , Marco Massari  2 , Lucia Palmisano  2 , Giuseppe Marano  11 , Margherita Chiamenti  12 , Laura Martinelli  13 , Silvia Franchi  13 , Carlo Pallotto  14 , Lorenzo Roberto Suardi  1   14 , Barbara Luciani Pasqua  15 , Marco Merli  9 , Plinio Fabiani  16 , Luca Bertolucci  16 , Beatrice Borchi  4 , Sara Modica  4 , Sara Moneta  6 , Giulia Marchetti  17 , Antonella d'Arminio Monforte  17 , Laura Stoppini  18 , Nadia Ferracchiato  18 , Stefania Piconi  19 , Claudio Fabbri  20 , Enrico Beccastrini  21 , Riccardo Saccardi  21 , Andrea Giacometti  22 , Sara Esperti  7 , Piera Pierotti  7 , Laura Bernini  23 , Claudia Bianco  23 , Sara Benedetti  5 , Alessandra Lanzi  5 , Paolo Bonfanti  24 , Marco Massari  25 , Spartaco Sani  26 , Annalisa Saracino  27 , Antonella Castagna  28 , Luigia Trabace  29 , Maria Lanza  30 , Daniele Focosi  30 , Alessandro Mazzoni  31 , Mauro Pistello  32 , Marco Falcone  1 ; TSUNAMI Study group
Collaborators, Affiliations
Randomized Controlled Trial

Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients With COVID-19 Pneumonia: A Randomized Clinical Trial

Francesco Menichetti et al. JAMA Netw Open. .

Erratum in

  • Errors in Results, Figure 1, Table 1, and Article Information.
    [No authors listed] [No authors listed] JAMA Netw Open. 2021 Dec 1;4(12):e2144236. doi: 10.1001/jamanetworkopen.2021.44236. JAMA Netw Open. 2021. PMID: 34932111 Free PMC article. No abstract available.
  • Error in Article Information.
    [No authors listed] [No authors listed] JAMA Netw Open. 2022 Jan 4;5(1):e2146944. doi: 10.1001/jamanetworkopen.2021.46944. JAMA Netw Open. 2022. PMID: 35040974 Free PMC article. No abstract available.

Abstract

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia.

Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia.

Design, setting, and participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible.

Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations.

Main outcomes and measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization.

Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04).

Conclusions and relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days.

Trial registration: ClinicalTrials.gov Identifier: NCT04716556.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Puoti reported receiving personal fees and nonfinancial support from Abbvie, grants and nonfinancial support from Gilead Science, and personal fees from Merck and Theratechnologies outside the submitted work. Dr Bonfanti reported receiving personal fees from Viiv, Gilead, Jannsen Pharmaceuticals, Merck, and Pfizer outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flowchart
Abbreviations: ITT, intention to treat population; mITT, modified intention to treat population; PP, per protocol population. aData not available for 3 patients (1 in convalescent plasma plus standard therapy group; 2 in standard therapy group).
Figure 2.
Figure 2.. Primary End Point in the Modified Intention-to-Treat Population, Subgroup Analysis
The primary end point was worsening respiratory failure or death within 30 days from randomization. Only 1 patient in the convalescent plasma (CP) plus standard therapy (ST) group and 7 in the ST group did not receive corticosteroids. LMWH indicates low–molecular weight heparin; NAb, neutralizing antibody.
Figure 3.
Figure 3.. Primary End Point Distribution According to the Study Groups and Baseline Partial Pressure Of Oxygen–to–Fraction of Inspired Oxygen (Pao2/Fio2) Ratio Categories in the Modified Intention to Treat Population
The primary end point was worsening respiratory failure or death within 30 days from randomization. Test for interaction: Pao2/Fio2 250 to 299 mm Hg vs 200 to 249 mm Hg, P > .99; Pao2/Fio2 300 mm Hg or greater vs 200 to 249 mm Hg, P = .06.
See this image and copyright information in PMC

References

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