Elena Diago-Sempere1, José Luis Bueno2, Aránzazu Sancho-López3, Elena Múñez Rubio4, Ferrán Torres5, Rosa Malo de Molina6, Ana Fernández-Cruz4, Isabel Salcedo de Diego1, Ana Velasco-Iglesias7, Concepción Payares-Herrera1, Inmaculada Casas Flecha8, Cristina Avendaño-Solà1, Rafael Duarte Palomino9, Antonio Ramos-Martínez4, Belén Ruiz-Antorán1. 1. Clinical Pharmacology Department, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro - Segovia de Arana, c/ Manuel de Falla 1, 28222, Madrid, Spain. 2. Hemotherapy & Apheresis Units, Hematology and Hemotherapy Department, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. 3. Clinical Pharmacology Department, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro - Segovia de Arana, c/ Manuel de Falla 1, 28222, Madrid, Spain. Aranzazu.sancho@salud.madrid.org. 4. Internal Medicine Department, Infectious diseases unit, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. 5. Clinical Pharmacology Department, Hospital Clínic Barcelona, Medical Statistics core facility - IDIBAPS, Barcelona, Spain. 6. Pneumology Department, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. 7. IIS Puerta de Hierro - Segovia de Arana, Madrid, Spain. 8. Flu and Respiratory Virus Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain. 9. Hematology and Hemotherapy Department, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
Abstract
BACKGROUND: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. At the time this clinical trial was planned, there were no available vaccine or therapeutic agents with proven efficacy, but the severity of the condition prompted the use of several pharmacological and non-pharmacological interventions. It has long been hypothesized that the use of convalescent plasma (CP) from infected patients who have developed an effective immune response is likely to be an option for the treatment of patients with a variety of severe acute respiratory infections (SARI) of viral etiology. The aim of this study is to assess the efficacy and safety of convalescent plasma in adult patients with severe COVID-19 pneumonia. METHODS/ DESIGN: The ConPlas-19 study is a multicenter, randomized, open-label controlled trial. The study has been planned to include 278 adult patients hospitalized with severe COVID-19 infection not requiring mechanical ventilation (invasive or non-invasive). Subjects are randomly assigned in a 1:1 ratio (139 per treatment arm), stratified by center, to receive intravenously administered CP (single infusion) plus SOC or SOC alone, and are to be followed for 30 days. The primary endpoint of the study is the proportion of patients that progress to category 5, 6, or 7 (on the 7-point ordinal scale proposed by the WHO) at day 15. Interim analyses for efficacy and/or futility will be conducted once 20%, 40%, and 60% of the planned sample size are enrolled and complete D15 assessment. DISCUSSION: This clinical trial is designed to evaluate the efficacy and safety of passive immunotherapy with convalescent plasma for the treatment of adult patients hospitalized with COVID-19. The results of this study are expected to contribute to establishing the potential place of CP in the therapeutics for a new viral disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT04345523 . Registered on 30 March, 2020. First posted date: April 14, 2020.
BACKGROUND: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. At the time this clinical trial was planned, there were no available vaccine or therapeutic agents with proven efficacy, but the severity of the condition prompted the use of several pharmacological and non-pharmacological interventions. It has long been hypothesized that the use of convalescent plasma (CP) from infected patients who have developed an effective immune response is likely to be an option for the treatment of patients with a variety of severe acute respiratory infections (SARI) of viral etiology. The aim of this study is to assess the efficacy and safety of convalescent plasma in adult patients with severe COVID-19 pneumonia. METHODS/ DESIGN: The ConPlas-19 study is a multicenter, randomized, open-label controlled trial. The study has been planned to include 278 adult patients hospitalized with severe COVID-19 infection not requiring mechanical ventilation (invasive or non-invasive). Subjects are randomly assigned in a 1:1 ratio (139 per treatment arm), stratified by center, to receive intravenously administered CP (single infusion) plus SOC or SOC alone, and are to be followed for 30 days. The primary endpoint of the study is the proportion of patients that progress to category 5, 6, or 7 (on the 7-point ordinal scale proposed by the WHO) at day 15. Interim analyses for efficacy and/or futility will be conducted once 20%, 40%, and 60% of the planned sample size are enrolled and complete D15 assessment. DISCUSSION: This clinical trial is designed to evaluate the efficacy and safety of passive immunotherapy with convalescent plasma for the treatment of adult patients hospitalized with COVID-19. The results of this study are expected to contribute to establishing the potential place of CP in the therapeutics for a new viral disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT04345523 . Registered on 30 March, 2020. First posted date: April 14, 2020.
Authors: 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 Journal: J Clin Invest Date: 2021-10-15 Impact factor: 14.808