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)
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doi:10.1007/s00330-020-06879-6{ 'indexed': {'date-parts': [[2024, 3, 29]], 'date-time': '2024-03-29T06:35:53Z', 'timestamp': 1711694153702},
'reference-count': 41,
'publisher': 'Public Library of Science (PLoS)',
'issue': '3',
'license': [ { 'start': { 'date-parts': [[2021, 3, 3]],
'date-time': '2021-03-03T00:00:00Z',
'timestamp': 1614729600000},
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'abstract': '<jats:sec id="sec001">\n'
'<jats:title>Background</jats:title>\n'
'<jats:p>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.</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec002">\n'
'<jats:title>Methods and findings</jats:title>\n'
'<jats:p>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) '
'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, <jats:italic>p</jats:italic> > 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 <jats:italic>p =</jats:italic> 0.246), mechanical ventilation 17.9% versus 6.7% '
'(OR 3.04, 95% CI 0.54–17.17, <jats:italic>p =</jats:italic> 0.246), and prolonged '
'hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19–2.10, <jats:italic>p '
'=</jats:italic> 0.554) in the early versus deferred CP group, respectively. The viral '
'clearance rate on day 3 (26% versus 8%, <jats:italic>p =</jats:italic> 0.204) and day 7 (38% '
'versus 19%, <jats:italic>p =</jats:italic> 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.</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec003">\n'
'<jats:title>Conclusions</jats:title>\n'
'<jats:p>In 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.</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec004">\n'
'<jats:title>Trial registration</jats:title>\n'
'<jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" '
'xlink:href="https://clinicaltrials.gov/ct2/show/NCT04375098" '
'xlink:type="simple">NCT04375098</jats:ext-link>.</jats:p>\n'
'</jats:sec>',
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