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

被引：52

作者：

Menichetti, Francesco ^{[1
]}

Popoli, Patrizia ^{[2
]}

Puopolo, Maria ^{[3
]}

Spila Alegiani, Stefania ^{[2
]}

Tiseo, Giusy ^{[1
]}

Bartoloni, Alessandro ^{[4
]}

De Socio, Giuseppe Vittorio ^{[5
]}

Luchi, Sauro ^{[6
]}

Blanc, Pierluigi ^{[7
]}

Puoti, Massimo ^{[8
,9
]}

Toschi, Elena ^{[10
]}

Massari, Marco ^{[2
,25
]}

Palmisano, Lucia ^{[2
]}

Marano, Giuseppe ^{[11
]}

Chiamenti, Margherita ^{[12
]}

Martinelli, Laura ^{[13
]}

Franchi, Silvia ^{[13
]}

Pallotto, Carlo ^{[14
]}

Suardi, Lorenzo Roberto ^{[1
,14
]}

Luciani Pasqua, Barbara ^{[15
]}

Merli, Marco ^{[9
]}

Fabiani, Plinio ^{[16
]}

Bertolucci, Luca ^{[16
]}

Borchi, Beatrice ^{[4
]}

Modica, Sara ^{[4
]}

Moneta, Sara ^{[6
]}

Marchetti, Giulia ^{[17
]}

d'Arminio Monforte, Antonella ^{[17
]}

Stoppini, Laura ^{[18
]}

Ferracchiato, Nadia ^{[18
]}

Piconi, Stefania ^{[19
]}

Fabbri, Claudio ^{[20
]}

Beccastrini, Enrico ^{[21
]}

Saccardi, Riccardo ^{[21
]}

Giacometti, Andrea ^{[22
]}

Esperti, Sara ^{[7
]}

Pierotti, Piera ^{[7
]}

Bernini, Laura ^{[23
]}

Bianco, Claudia ^{[23
]}

Benedetti, Sara ^{[5
]}

Lanzi, Alessandra ^{[5
]}

Bonfanti, Paolo ^{[24
]}

Sani, Spartaco ^{[26
]}

Saracino, Annalisa ^{[27
]}

Castagna, Antonella ^{[28
]}

Trabace, Luigia ^{[29
]}

Lanza, Maria ^{[30
]}

Focosi, Daniele ^{[30
]}

Mazzoni, Alessandro ^{[31
]}

Pistello, Mauro ^{[32
]}

机构：

[1] Univ Pisa, Azienda Osped Univ Pisana, Dept Clin & Expt Med, Infect Dis Unit, Pisa, Italy

[2] Natl Ctr Drug Res & Evaluat, Ist Super Sanita, Rome, Italy

[3] Ist Super Sanita, Dept Neurosci, Rome, Italy

[4] Careggi Univ Hosp, Florence Dept Med, Infect & Trop Dis Unit, Florence, Italy

[5] Univ Perugia, Santa Maria Misericordia Hosp, Clin Infect Dis, Perugia, Italy

[6] Hosp Lucca, Infect Dis Unit, Lucca, Italy

[7] Osped S Maria Annunziata, Infect Dis, Florence, Italy

[8] Univ Milano Bicocca, Sch Med, Milan, Italy

[9] Grande Osped Metropolitano Niguarda, Azienda Socio Sanitaria Terr ASST, Milan, Italy

[10] Ist Super Sanita, Res Coordinat & Support Serv CoRi, Rome, Italy

[11] Italian Natl Blood Ctr, Rome, Italy

[12] Carlo Poma Hosp, Unit Infect Dis, Mantua, Italy

[13] Osped Citta Castello, Internal Med, Unita Sanitaria Locale USL Umbria 1, Citta Castello, Italy

[14] San Giuseppe Hosp, Infect Dis Unit, Azienda USL Toscana Ctr, Empoli, Italy

[15] Azienda Osped Perugia, Ctr Reg Sangue, Serv Immunotrasfus, Perugia, Italy

[16] Osped Unico Versilia, Internal Med, Lido Di Camaiore, Italy

[17] ASST Santi Paolo & Carlo Univ Hosp, Dept Hlth Sci, Infect Dis Unit, Milan, Italy

[18] Osped Foligno, Internal Med, Foligno, Italy

[19] Azienda Osped Lecco, Infect Dis, Lecce, Italy

[20] Osped San Jacopo, Infect Dis, Pistoia, Italy

[21] Careggi Univ Hosp, Cell Therapy & Transfus Med, Florence, Italy

[22] Azienda Osped Univ, Osped Riuniti Ancona, Ancona, Italy

[23] Arezzo Hosp, Div Infect Dis, Arezzo, Italy

[24] Univ Milano Bicocca, Dept Infect Dis, ASST Monza, Milan, Italy

[25] Ist Ricovero & Cura Carattere Sci IRCCS Reggio Em, Infect Dis Unit, Azienda USL, Reggio Emilia, Italy

[26] Livorno Hosp, Infect Dis, Livorno, Italy

[27] Bari Univ Hosp, Div Infect Dis, Bari, Italy

[28] Univ Vita Salute San Raffaele, Infect Dis, IRCCS Osped San Raffaele, Milan, Italy

[29] Univ Foggia, Dept Expt & Clin Med, Foggia, Italy

[30] Pisa Univ Hosp, North Western Tuscany Blood Bank, Pisa, Italy

[31] Pisa Univ Hosp, Div Transfus Med & Transplant Biol, Pisa, Italy

[32] Univ Pisa, Univ Hosp Pisa, Div Virol, Dept Translat Res,Retrovirus Ctr, Pisa, Italy

来源：

JAMA NETWORK OPEN | 2021年 / 4卷 / 11期

关键词：

D O I：

10.1001/jamanetworkopen.2021.36246

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 (Pao(2)/Fio(2)) 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 (Pao(2)/Fio(2) 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.

引用

页数：12

共 27 条

[1] Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial) [J].

Agarwal, Anup ;

Mukherjee, Aparna ;

Kumar, Gunjan ;

Chatterjee, Pranab ;

Bhatnagar, Tarun ;

Malhotra, Pankaj .

BMJ-BRITISH MEDICAL JOURNAL, 2020, 371

[2]

Agenzia Italiana del Farmaco (AIFA), TRATT UT NEI PAZ CO

[3] Reporting of Participant Race, Sex, and Socioeconomic Status in Randomized Clinical Trials in General Medical Journals, 2015 vs 2019 [J].

Alegria, Mikhaila ;

Sud, Shawn ;

Steinberg, Benjamin E. ;

Gai, Nan ;

Siddiqui, Asad .

JAMA NETWORK OPEN, 2021, 4 (05)

[4] Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease [J].

AlQahtani, Manaf ;

Abdulrahman, Abdulkarim ;

Almadani, Abdulrahman ;

Alali, Salman Yousif ;

Al Zamrooni, Alaa Mahmood ;

Hejab, Amal Hamza ;

Conroy, Ronan M. ;

Wasif, Pearl ;

Otoom, Sameer ;

Atkin, Stephen L. ;

Abduljalil, Manal .

SCIENTIFIC REPORTS, 2021, 11 (01)

[5]

Amanat Fatima, 2020, Curr Protoc Microbiol, V58, pe108, DOI 10.1002/cpmc.108

[6] World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects [J].

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2013, 310 (20) :2191-2194

[7]

Avendano-Sola C, 2020, CONVALESCENT PLASMA, DOI 10.1101/2020.08.26.20182444

[8]

Bajpai M., 2020, EFFICACY CONVALESCEN

[9] Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: A randomized phase II clinical trial [J].

Balcells, Maria Elvira ;

Rojas, Luis ;

Le Corre, Nicole ;

Martinez-Valdebenito, Constanza ;

Ceballos, Maria Elena ;

Ferres, Marcela ;

Chang, Mayling ;

Vizcaya, Cecilia ;

Mondaca, Sebastian ;

Huete, Alvaro ;

Castro, Ricardo ;

Sarmiento, Mauricio ;

Villarroel, Luis ;

Pizarro, Alejandra ;

Ross, Patricio ;

Santander, Jaime ;

Lara, Barbara ;

Ferrada, Marcela ;

Vargas-Salas, Sergio ;

Beltran-Pavez, Carolina ;

Soto-Rifo, Ricardo ;

Valiente-Echeverria, Fernando ;

Caglevic, Christian ;

Mahave, Mauricio ;

Selman, Carolina ;

Gazitua, Raimundo ;

Briones, Jose Luis ;

Villarroel-Espindola, Franz ;

Balmaceda, Carlos ;

Espinoza, Manuel A. ;

Pereira, Jaime ;

Nervi, Bruno .

PLOS MEDICINE, 2021, 18 (03)

[10] Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients [J].

Bellan, Mattia ;

Patti, Giuseppe ;

Hayden, Eyal ;

Azzolina, Danila ;

Pirisi, Mario ;

Acquaviva, Antonio ;

Aimaretti, Gianluca ;

Aluffi Valletti, Paolo ;

Angilletta, Roberto ;

Arioli, Roberto ;

Avanzi, Gian Carlo ;

Avino, Gianluca ;

Balbo, Piero Emilio ;

Baldon, Giulia ;

Baorda, Francesca ;

Barbero, Emanuela ;

Baricich, Alessio ;

Barini, Michela ;

Barone-Adesi, Francesco ;

Battistini, Sofia ;

Beltrame, Michela ;

Bertoli, Matteo ;

Bertolin, Stephanie ;

Bertolotti, Marinella ;

Betti, Marta ;

Bobbio, Flavio ;

Boffano, Paolo ;

Boglione, Lucio ;

Borre, Silvio ;

Brucoli, Matteo ;

Calzaducca, Elisa ;

Cammarata, Edoardo ;

Cantaluppi, Vincenzo ;

Cantello, Roberto ;

Capponi, Andrea ;

Carriero, Alessandro ;

Casciaro, Francesco Giuseppe ;

Castello, Luigi Mario ;

Ceruti, Federico ;

Chichino, Guido ;

Chirico, Emilio ;

Cisari, Carlo ;

Cittone, Micol Giulia ;

Colombo, Crizia ;

Comi, Cristoforo ;

Croce, Eleonora ;

Daffara, Tommaso ;

Danna, Pietro ;

Della Corte, Francesco ;

De Vecchi, Simona .

SCIENTIFIC REPORTS, 2020, 10 (01)

← 1 2 3 →