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/Fio2ratio <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.

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 / Menichetti F.; Popoli P.; Puopolo M.; Spila Alegiani S.; Tiseo G.; Bartoloni A.; De Socio G.V.; Luchi S.; Blanc P.; Puoti M.; Toschi E.; Massari M.; Palmisano L.; Marano G.; Chiamenti M.; Martinelli L.; Franchi S.; Pallotto C.; Suardi L.R.; Luciani Pasqua B.; Merli M.; Fabiani P.; Bertolucci L.; Borchi B.; Modica S.; Moneta S.; Marchetti G.; D'Arminio Monforte A.; Stoppini L.; Ferracchiato N.; Piconi S.; Fabbri C.; Beccastrini E.; Saccardi R.; Giacometti A.; Esperti S.; Pierotti P.; Bernini L.; Bianco C.; Benedetti S.; Lanzi A.; Bonfanti P.; Massari M.; Sani S.; Saracino A.; Castagna A.; Trabace L.; Lanza M.; Focosi D.; Mazzoni A.; Pistello M.; Falcone M.. - In: JAMA NETWORK OPEN. - ISSN 2574-3805. - ELETTRONICO. - 4:(2021), pp. e2136246-e2136246. [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

Bartoloni A.;Modica S.;Falcone M.
2021

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/Fio2ratio <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.
2021
4
e2136246
e2136246
Menichetti F.; Popoli P.; Puopolo M.; Spila Alegiani S.; Tiseo G.; Bartoloni A.; De Socio G.V.; Luchi S.; Blanc P.; Puoti M.; Toschi E.; Massari M.; Palmisano L.; Marano G.; Chiamenti M.; Martinelli L.; Franchi S.; Pallotto C.; Suardi L.R.; Luciani Pasqua B.; Merli M.; Fabiani P.; Bertolucci L.; Borchi B.; Modica S.; Moneta S.; Marchetti G.; D'Arminio Monforte A.; Stoppini L.; Ferracchiato N.; Piconi S.; Fabbri C.; Beccastrini E.; Saccardi R.; Giacometti A.; Esperti S.; Pierotti P.; Bernini L.; Bianco C.; Benedetti S.; Lanzi A.; Bonfanti P.; Massari M.; Sani S.; Saracino A.; Castagna A.; Trabace L.; Lanza M.; Focosi D.; Mazzoni A.; Pistello M.; Falcone M.
File in questo prodotto:
File Dimensione Formato  
menichetti_2021_oi_211022_1642100496.70738.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 1.02 MB
Formato Adobe PDF
1.02 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1258317
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 43
  • ???jsp.display-item.citation.isi??? 45
social impact