A multicenter randomized open-label clinical trial for convalescent plasma in patients hospitalized with COVID-19 pneumonia
Cristina Avendaño-Solá, Antonio Ramos-Martínez, Elena Muñez-Rubio, Belen Ruiz-Antorán, Rosa Malo de Molina, Ferran Torres, Ana Fernández-Cruz, Jorge Calderón-Parra, Concepcion Payares-Herrera, Alberto Díaz de Santiago, Irene Romera-Martínez, Ilduara Pintos, Jaime Lora-Tamayo, Mikel Mancheño-Losa, Maria L Paciello, A L Martínez-González, Julia Vidán-Estévez, Maria J Nuñez-Orantos, Maria Isabel Saez-Serrano, Maria L Porras-Leal, Maria C Jarilla-Fernández, Paula Villares, Jaime Pérez de Oteyza, Ascension Ramos-Garrido, Lydia Blanco, Maria E Madrigal-Sánchez, Martin Rubio-Batllés, Ana Velasco-Iglesias, José R Paño-Pardo, J A Moreno-Chulilla, Eduardo Muñiz-Díaz, Inmaculada Casas-Flecha, Mayte Pérez-Olmeda, Javier García-Pérez, Jose Alcamí, Jose L Bueno, Rafael F Duarte, ConPlas-19 Study Group, Maria Abando, Jorge Alba Fernandez, Ines Almagro-Treviño, Albert Altes-Hernández, Laura Analia-Maglio, Borja Andrades, Giselle Victoria Andujar-Troncoso, Javier Anguita Velasco, Alicia Aranguren Azparren, Cristina Arbona-Castaño, Francisco Arnaiz, Itziar Arrieta, Jose Luis Arroyo Rodríguez, Ana M. Arruga-Manzano, Cristina Avendaño-Solá, Monica Baldrich, Carmen Ballester, Moncef Belhassen García, Margarita Berberana Fernández de Murias, José Javier Blanch Sancho, Lydia Blanco, Virginia Blasco, Alba Bosch, José Luis Bueno Cabrera, Ruth Caballero-Asensio, Antonio Caballero-Bermejo, Jorge Calderon Parra, Juan M. Calvo Mayo, Lourdes Carmona, Antoni Castro, Gustavo Adolfo Centeno Soto, Damián Cubillas, Cristina Daroca-Ponce de Leon, Ignacio de la Fuente Graciani, Marisa de la Rica, Ignacio de los Santos Gil, Dolores del Puerto García, Elena Diago-Sempere, Alberto Diaz de Santiago, José M Domingo-Morera, Oscar Sanz Pelaez, Rafael J Duarte Palomino, Carlos Jesús Dueñas Gutierrez, Pedro Durán del Campo, Gabriela Ene, Brigida Esteban, Vicente Estrada Perez, María del Carmen Fariñas, Ana Fernández-Cruz, Elena Flores Ballester, Antonia Flor-Pérez, Ainhoa Garaialde, Beatriz Garcia, Concepción Garcia García, José Antonio Garcia-Erce, Lucio Jesús García-Fraile, Marta Garcia-Martinez-Avial, Ana Maria Garcia-Pérez, Santiago Garcia-Ruiz, Luz M. Gonzalez del Castillo, Alicia Gonzalez Mena, M. Isabel Gonzalez-Fraile, Francisco Javier Gonzalez-Gasca, Claudia Gonzalez-Rico, Victoria Paz González-Rodríguez, María Gracia Ruiz de Alda, Luisa Guerra-Domínguez, Elena Gutierrez Gamarra, Natalia C. Hernandez-de-León-de-Castro, Jose Antonio Iribarren, Anny Jaramillo-Rodríguez, Estibaliz Jarauta-Simón, María del C. Jarilla-Fernández, Teresa Jimenez-Marco, Jesús Jimenez-Megias, Alfredo Jover-Saenz, Hernando Knobel, Rocio Layunta, Olga López Villar, Juan C. Lopez-Aguilar, Jaime Lora Tamayo, Pilar Lozano, Carlos Lumbreras-Bermejo, Marina Machado, María Elena Madrigal-Sánchez, Rosa Malo de Molina, Mikel Mancheño-Losa, Raquel Marti, M Carmen Martin-Alonso, Javier Martinez Sanz, Ángel L. Martinez-González, Joaquín Martinez-López, Amador Martín-Recio, Fernando Mateos Rodriguez, Armando V. Mena-Duran, Anna Millán, Itxaso Mora, José Antonio Moreno Chulilla, Gemma Moreno, José Luis Mostaza Fernández, Elena Muñez Rubio, Eduardo Muñiz-Diaz, María Pilar Muñoz Valbuena, Javier Murillas, Ana M Ojea Perez, Irati Ormazábal Vélez, José Antonio Oteo Revuelta, María Liz Paciello, Angel Luis Pajares Herraiz, Jose Ramón Paño-Pardo, Concepcion Payares-Herrera, Esther Pena Carbo, Jaime Perez de Oteyza, Sonia Pérez Gonzalez, Ilduara Pintos Pascual, Ana B. Polo-Escriche, María Lourdes Porras-Leal, Francisco Puchades-Gimeno, José Ramón Yuste Ara, Ascensión Ramos-Garrido, Antonio Ramos-Martinez, Sara Rodriguez, Andrea Rodriguez, Irene Romera, Iñigo Romon Alonso, Martín Rubio-Batlles, Belen Ruiz-Antoran, Maria L. Ruiz-Ayala, Belen Sabada-Diaz de Rada, María Isabel Sáez Serrano, Isabel Salcedo, Monica Sánchez, Angel Sanchez Castaño, Juan Manuel Sanchez Villegas, Santiago Sánchez, Raquel Sandoval, Paula Santibañez Saez, Carlos Sola Lapeña, Ferran Torres, Andrea Torres López, Sabin Urcelay-Uranga, Juan Carlos Vallejo, Alvaro Veiga-Alvarez, Ana Velasco-Iglesias, Isabel Vicuña Andrés, Julia Vidan Estévez, Paula Villares, Carolina Villegas Da Ros, Cristina Avendaño-Solá, Antonio Ramos-Martínez, Elena Muñez-Rubio, Belen Ruiz-Antorán, Rosa Malo de Molina, Ferran Torres, Ana Fernández-Cruz, Jorge Calderón-Parra, Concepcion Payares-Herrera, Alberto Díaz de Santiago, Irene Romera-Martínez, Ilduara Pintos, Jaime Lora-Tamayo, Mikel Mancheño-Losa, Maria L Paciello, A L Martínez-González, Julia Vidán-Estévez, Maria J Nuñez-Orantos, Maria Isabel Saez-Serrano, Maria L Porras-Leal, Maria C Jarilla-Fernández, Paula Villares, Jaime Pérez de Oteyza, Ascension Ramos-Garrido, Lydia Blanco, Maria E Madrigal-Sánchez, Martin Rubio-Batllés, Ana Velasco-Iglesias, José R Paño-Pardo, J A Moreno-Chulilla, Eduardo Muñiz-Díaz, Inmaculada Casas-Flecha, Mayte Pérez-Olmeda, Javier García-Pérez, Jose Alcamí, Jose L Bueno, Rafael F Duarte, ConPlas-19 Study Group, Maria Abando, Jorge Alba Fernandez, Ines Almagro-Treviño, Albert Altes-Hernández, Laura Analia-Maglio, Borja Andrades, Giselle Victoria Andujar-Troncoso, Javier Anguita Velasco, Alicia Aranguren Azparren, Cristina Arbona-Castaño, Francisco Arnaiz, Itziar Arrieta, Jose Luis Arroyo Rodríguez, Ana M. Arruga-Manzano, Cristina Avendaño-Solá, Monica Baldrich, Carmen Ballester, Moncef Belhassen García, Margarita Berberana Fernández de Murias, José Javier Blanch Sancho, Lydia Blanco, Virginia Blasco, Alba Bosch, José Luis Bueno Cabrera, Ruth Caballero-Asensio, Antonio Caballero-Bermejo, Jorge Calderon Parra, Juan M. Calvo Mayo, Lourdes Carmona, Antoni Castro, Gustavo Adolfo Centeno Soto, Damián Cubillas, Cristina Daroca-Ponce de Leon, Ignacio de la Fuente Graciani, Marisa de la Rica, Ignacio de los Santos Gil, Dolores del Puerto García, Elena Diago-Sempere, Alberto Diaz de Santiago, José M Domingo-Morera, Oscar Sanz Pelaez, Rafael J Duarte Palomino, Carlos Jesús Dueñas Gutierrez, Pedro Durán del Campo, Gabriela Ene, Brigida Esteban, Vicente Estrada Perez, María del Carmen Fariñas, Ana Fernández-Cruz, Elena Flores Ballester, Antonia Flor-Pérez, Ainhoa Garaialde, Beatriz Garcia, Concepción Garcia García, José Antonio Garcia-Erce, Lucio Jesús García-Fraile, Marta Garcia-Martinez-Avial, Ana Maria Garcia-Pérez, Santiago Garcia-Ruiz, Luz M. Gonzalez del Castillo, Alicia Gonzalez Mena, M. Isabel Gonzalez-Fraile, Francisco Javier Gonzalez-Gasca, Claudia Gonzalez-Rico, Victoria Paz González-Rodríguez, María Gracia Ruiz de Alda, Luisa Guerra-Domínguez, Elena Gutierrez Gamarra, Natalia C. Hernandez-de-León-de-Castro, Jose Antonio Iribarren, Anny Jaramillo-Rodríguez, Estibaliz Jarauta-Simón, María del C. Jarilla-Fernández, Teresa Jimenez-Marco, Jesús Jimenez-Megias, Alfredo Jover-Saenz, Hernando Knobel, Rocio Layunta, Olga López Villar, Juan C. Lopez-Aguilar, Jaime Lora Tamayo, Pilar Lozano, Carlos Lumbreras-Bermejo, Marina Machado, María Elena Madrigal-Sánchez, Rosa Malo de Molina, Mikel Mancheño-Losa, Raquel Marti, M Carmen Martin-Alonso, Javier Martinez Sanz, Ángel L. Martinez-González, Joaquín Martinez-López, Amador Martín-Recio, Fernando Mateos Rodriguez, Armando V. Mena-Duran, Anna Millán, Itxaso Mora, José Antonio Moreno Chulilla, Gemma Moreno, José Luis Mostaza Fernández, Elena Muñez Rubio, Eduardo Muñiz-Diaz, María Pilar Muñoz Valbuena, Javier Murillas, Ana M Ojea Perez, Irati Ormazábal Vélez, José Antonio Oteo Revuelta, María Liz Paciello, Angel Luis Pajares Herraiz, Jose Ramón Paño-Pardo, Concepcion Payares-Herrera, Esther Pena Carbo, Jaime Perez de Oteyza, Sonia Pérez Gonzalez, Ilduara Pintos Pascual, Ana B. Polo-Escriche, María Lourdes Porras-Leal, Francisco Puchades-Gimeno, José Ramón Yuste Ara, Ascensión Ramos-Garrido, Antonio Ramos-Martinez, Sara Rodriguez, Andrea Rodriguez, Irene Romera, Iñigo Romon Alonso, Martín Rubio-Batlles, Belen Ruiz-Antoran, Maria L. Ruiz-Ayala, Belen Sabada-Diaz de Rada, María Isabel Sáez Serrano, Isabel Salcedo, Monica Sánchez, Angel Sanchez Castaño, Juan Manuel Sanchez Villegas, Santiago Sánchez, Raquel Sandoval, Paula Santibañez Saez, Carlos Sola Lapeña, Ferran Torres, Andrea Torres López, Sabin Urcelay-Uranga, Juan Carlos Vallejo, Alvaro Veiga-Alvarez, Ana Velasco-Iglesias, Isabel Vicuña Andrés, Julia Vidan Estévez, Paula Villares, Carolina Villegas Da Ros
Abstract
BACKGROUNDPassive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19. Evidence from controlled clinical trials is inconclusive.METHODSWe conducted a randomized, open-label, controlled clinical trial at 27 hospitals in Spain. Patients had to be admitted for COVID-19 pneumonia within 7 days from symptom onset and not on mechanical ventilation or high-flow oxygen devices. Patients were randomized 1:1 to treatment with CP in addition to standard of care (SOC) or to the control arm receiving only SOC. The primary endpoint was the proportion of patients in categories 5 (noninvasive ventilation or high-flow oxygen), 6 (invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), or 7 (death) at 14 days. Primary analysis was performed in the intention-to-treat population.RESULTSBetween April 4, 2020, and February 5, 2021, 350 patients were randomly assigned to either CP (n = 179) or SOC (n = 171). At 14 days, proportion of patients in categories 5, 6, or 7 was 11.7% in the CP group versus 16.4% in the control group (P = 0.205). The difference was greater at 28 days, with 8.4% of patients in categories 5-7 in the CP group versus 17.0% in the control group (P = 0.021). The difference in overall survival did not reach statistical significance (HR 0.46, 95% CI 0.19-1.14, log-rank P = 0.087).CONCLUSIONCP showed a significant benefit in preventing progression to noninvasive ventilation or high-flow oxygen, invasive mechanical ventilation or ECMO, or death at 28 days. The effect on the predefined primary endpoint at 14 days and the effect on overall survival were not statistically significant.TRIAL REGISTRATIONClinicaltrials.gov, NCT04345523.FUNDINGGovernment of Spain, Instituto de Salud Carlos III.
Keywords: COVID-19; Immunotherapy.
Conflict of interest statement
Conflict of interest: The authors have declared that no conflict of interest exists.
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Source: PubMed