Convalescent Plasma for COVID-19: A multicenter, randomized clinical trial

Avendaño-Solà et al., medRxiv, doi:10.1101/2020.08.26.20182444, ConPlas-19, NCT04345523

Sep 2020

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Early terminated RCT with 81 hospitalized patients, 38 treated with convalescent plasma, showing lower progression with treatment.

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risk of death, 88.3% lower, RR 0.12, p = 0.12, treatment 0 of 38 (0.0%), control 4 of 43 (9.3%), NNT 11, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 29.

risk of progression, 93.0% lower, RR 0.07, p = 0.01, treatment 0 of 38 (0.0%), control 7 of 43 (16.3%), NNT 6.1, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 29, progression to categories 5-7.

risk of progression, 91.9% lower, RR 0.08, p = 0.03, treatment 0 of 38 (0.0%), control 6 of 43 (14.0%), NNT 7.2, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 15, progression to categories 5-7, primary outcome.

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Avendaño-Solà et al., 29 Sep 2020, Randomized Controlled Trial, Spain, peer-reviewed, 38 authors, study period 4 April, 2020 - 10 July, 2020, average treatment delay 8.0 days, trial NCT04345523 (history) (ConPlas-19).

This Paper Conv. Plasma All

Convalescent Plasma for COVID-19: A multicenter, randomized clinical trial

C Avendaño-Solà, A Ramos-Martínez, E Muñez-Rubio, B Ruiz-Antorán, R Malo De Molina, F Torres, A Fernández-Cruz, A Callejas-Díaz, J Calderón, C Payares-Herrera, I Salcedo, I Romera, J Lora-Tamayo, M Mancheño-Losa, M L Paciello, C Villegas, V Estrada, I Saez-Serrano, M L Porras-Leal, M C Jarilla-Fernández, J R Paño-Pardo JR, J A Moreno-Chulilla, I Arrieta-Aldea, A Bosch, M Belhassen-Garcia, O López-Villar, A Ramos-Garrido, L Blanco, M E Madrigal-Sánchez, E Contreras, E Muñiz-Díaz, J M Domingo-Morera, I Casas-Flecha, M Pérez-Olmeda, Javier Garcia-Pérez, J Alcamí, J L Bueno, R F Duarte

doi:10.1101/2020.08.26.20182444

Background: Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. Methods: We conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. Results: The trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. Conclusions : Convalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523). .

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DOI record: { "DOI": "10.1101/2020.08.26.20182444", "URL": "http://dx.doi.org/10.1101/2020.08.26.20182444", "abstract": "ABSTRACTBackgroundPassive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking.MethodsWe conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15.ResultsThe trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies.ConclusionsConvalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. 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Late treatment
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