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
Mortality 88% improvement lower risk ← → higher risk Progression 93% Progression b 92% primary Conv. Plasma  ConPlas-19  LATE TREATMENT RCT Is late treatment with convalescent plasma beneficial? RCT 81 patients in Spain (April - July 2020) Lower progression with convalescent plasma (p=0.013) c19early.org Avendaño-Solà et al., medRxiv, September 2020 0 0.5 1 1.5 2+ RR
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.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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).
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2025 Spain United Kingdom Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Georgia Switzerland Bosnia-Herzegovina Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR Spain favored high-profit treatments.The average efficacy of treatments was very low.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2025 Spain United Kingdom Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Georgia Switzerland Bosnia-Herzegovina Ukraine Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore New Zealand Malawi Czechia Mongolia Israel Trinidad and Tobago North Macedonia Belarus Qatar Panama Serbia Syria Spain favored high-profit treatments.The average efficacy was very low.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
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). .
References
Beigel, Tomashek, Dodd, Remdesivir for the treatment of Covid-19 -preliminary report, N Engl J Med, doi:10.1056/NEJMoa2007764
Califf, Hernandez, Landray, Weighing the Benefits and Risks of Proliferating Observational Treatment Assessments.Observational Cacophony, Randomized Harmony, JAMA, doi:10.1001/jama.2020.13319
Cao, Wang, Wen, A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19, New England Journal of Medicine
Cavalcanti, Zampieri, Rosa, Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19, New England Journal of Medicine
Chen, Xiong, Bao, Shi, Convalescent plasma as a potential therapy for COVID-19, Lancet Infect Dis
Gharbharan, Jordans, Geurtsvankessel, Convalescent Plasma for COVID-19. A randomized clinical trial, Medrxiv
Joyner, Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience, doi:10.1101/2020.08.12.20169359v1
Li, Zhang, Hu, Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial, JAMA. Published, doi:10.1001/jama.2020.10044
Mair-Jenkins, Saavedra-Campos, Baillie, The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis, J Infect Dis
Petkova, Antman, Troxel, Pooling Data From Individual Clinical Trials in the COVID-19 Era, JAMA Published Online, doi:10.1001/jama.2020.13042
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The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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 <jats:italic>Instituto de Salud Carlos III;</jats:italic><jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04345523\">NCT04345523</jats:ext-link>).</jats:p></jats:sec>", "accepted": { "date-parts": [ [ 2020, 9, 29 ] ] }, "author": [ { "affiliation": [], "family": "Avendaño-Solà", "given": "C", "sequence": "first" }, { "affiliation": [], "family": "Ramos-Martínez", "given": "A", "sequence": "additional" }, { "affiliation": [], "family": "Muñez-Rubio", "given": "E", "sequence": "additional" }, { "affiliation": [], "family": "Ruiz-Antorán", "given": "B", "sequence": "additional" }, { "affiliation": [], "family": "de Molina", "given": "R Malo", "sequence": "additional" }, { "affiliation": [], "family": "Torres", "given": "F", "sequence": "additional" }, { "affiliation": [], "family": "Fernández-Cruz", "given": "A", "sequence": "additional" }, { "affiliation": [], "family": "Callejas-Díaz", "given": "A", "sequence": 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Late treatment
is less effective
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