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

Balcells et al., PLOS Medicine, doi:10.1371/journal.pmed.1003415, NCT04375098, Mar 2021

https://c19early.org/balcells.html

Small RCT with 28 early and 30 deferred (treated according to prespecified deterioration criteria) convalescent plasma patients, not showing significant differences. "Early" is relative, with a median of 5 days from symptom onset. 13 patients in the deferred group received plasma.

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risk of death, 247.4% higher, RR 3.47, p = 0.17, treatment 5 of 28 (17.9%), control 2 of 30 (6.7%), adjusted per study, odds ratio converted to relative risk, logistic regression, early vs. deferred.

risk of mechanical ventilation, 163.3% higher, RR 2.63, p = 0.22, treatment 5 of 28 (17.9%), control 2 of 30 (6.7%), adjusted per study, odds ratio converted to relative risk, logistic regression, early vs. deferred.

risk of progression, 23.3% higher, RR 1.23, p = 0.51, treatment 13 of 28 (46.4%), control 12 of 30 (40.0%), adjusted per study, odds ratio converted to relative risk, logistic regression, early vs. deferred.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Balcells et al., 3 Mar 2021, Randomized Controlled Trial, Chile, peer-reviewed, 32 authors, study period 10 May, 2020 - 18 July, 2020, average treatment delay 5.0 days, trial NCT04375098 (history).

This Paper Conv. Plasma All

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

María Elvira Balcells, Luis Rojas, Nicole Le Corre, Constanza Martínez-Valdebenito, María Elena Ceballos, Marcela Ferrés, Mayling Chang, Cecilia Vizcaya, Sebastián Mondaca, Álvaro Huete, Ricardo Castro, Mauricio Sarmiento, Luis Villarroel, Alejandra Pizarro, Patricio Ross, Jaime Santander, Bárbara Lara, Marcela Ferrada, Sergio Vargas-Salas, Carolina Beltrán-Pavez, Ricardo Soto-Rifo, Fernando Valiente-Echeverría, Christian Caglevic, Mauricio Mahave, Carolina Selman, Raimundo Gazitúa, José Luis Briones, Franz Villarroel-Espindola, Carlos Balmaceda, Manuel A Espinoza, Jaime Pereira, Bruno Nervi

PLOS Medicine, doi:10.1371/journal.pmed.1003415

Background Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. Methods and findings The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group)

Supporting information [22] ). (B) CT score 2 (Yang et al. [25] ). (C) CT score 3 (Pan et al. [23, 24] ). (TIF) S1

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DOI record: { "DOI": "10.1371/journal.pmed.1003415", "ISSN": [ "1549-1676" ], "URL": "http://dx.doi.org/10.1371/journal.pmed.1003415", "abstract": "\nBackground\nConvalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression.\n\n\nMethods and findings\nThe study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32–2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54–17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54–17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19–2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion.\n\n\nConclusions\nIn the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration.\n\n\nTrial registration\nNCT04375098.\n", "author": [ { "ORCID": "http://orcid.org/0000-0002-7223-9665", "affiliation": [], "authenticated-orcid": true, "family": "Balcells", "given": "María Elvira", "sequence": "first" }, { "ORCID": "http://orcid.org/0000-0002-0234-5876", "affiliation": [], "authenticated-orcid": true, "family": "Rojas", "given": "Luis", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-9361-4049", "affiliation": [], "authenticated-orcid": true, 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