Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses

著者: Hongchao Pan, Richárd Pető, Ana María Henao-Restrepo, Marie‐Pierre Préziosi, Vasee Moorthy, Quarraisha Abdool Karim, Marissa Alejandria, César Hernàndez García, Marie-Paule Kiény, Reza Malekzadeh, Srinivas Murthy, K. Srinath Reddy, Mirta Roses Periago, Pierre Abi Hanna, Akaki Abutidze, Florence Ader, Abdullah Al-Bader, Almonther Alhasawi, Emma Allum, Adhra Al‐Mawali, Athari Alotaibi, Carlos Álvarez, Sheila Appadoo, Derk L. Arts, Abdullah M. Asiri, Pål Aukrust, Andreas Barratt‐Due, Abebe Genetu Bayih, H. Beaumont, Samir Bellani, Virginia Benassi, Balram Bhargava, Mattia Branca, Heike Cappel-Porter, Nery Cerrato, Fadima Cheick Haidara, Ting Soo Chow, Nadia Como, Joe Eustace, Tamar Gabunia, Patricia García, Sheela Godbole, Eduardo Gotuzzo, Laimonas Griškevičius, Rasha Hamra, Mariam Hassan, Mohamed Hassany, David W. Hutton, Irmansyah Irmansyah, Ligita Jančorienė, Faryal Khamis, Jana Kirwan, Suresh Kumar, Peter Lennon, Gustavo Lopardo, Patrick Lydon, Nicola Magrini, Suzana Manevska, Oriol Manuel, Sybil McGinty, Marco T. Medina, María Lucía Mesa Rubio, María Consuelo Miranda, Jeremy Nel, Estêvão Portela Nunes, Markus Perola, Antonio Portolés, Menaldi Rasmin, Aun Raza, Helen Rees, Paula Reges, Chris Rogers, Kolawole Salami, Marina I. Salvadori, Mamatha Sauermann, Narvina Sinani, Samba O. Sow, Jonathan A C Sterne, Milena Stevanoviкј, Evelina Tacconelli, Fernando Maltêz, Mekonnen Teferi, Kari A.O. Tikkinen, Sven Trelle, Tengiz Tsertsvadze, Hala Zaid, John-Arne Røttingen, Soumya Swaminathan, Michael P. Ryan, Nevila Gjermeni, Esmeralda Meta, Damián Águila, Ignacio Alonso, Marcos Altamirano, María López Álvarez, Rodrigo Alzola, Verónica Arce, Patricia Arribillaga, Rafael Ávila, Juan Pablo Balbuena, Laura Barcelona, José Barletta, María Benedetti, Verónica Berdiñas, Julieta Burgui, Sabrina Caimi, Juan Carrillo, Juan Carrizo, Juan Castelli, Alexis Cazaux, Flavia Cervellino, Angelo Chalco, Viviana Chediack, Eleonora Cunto, N. D'Amico, Lautaro De Vedia, Carolina Delgado, Debora Di Pilla, Miguel Ángel Díaz, Pablo Díaz Aguiar, Cecilia Domínguez, Leonor Ellero, Javier Farina, José Rodrigo Espinosa Fernández, Roxana Ferreyra, Maria Maddalena Filippi, Carolina Fogar, Pablo S. Frare, Celeste Giudiche, Mariana L. Golikow, María Georgina Gomez, Laura Hermida, Mariano Hurtado, Mariela Jacobo, Martin Jaume, Diego Laplume, María Lescano, Nicolás Lista, Flavia Loiacono, Ana Belen López, Marcelo Losso, Cecilia Luna, Sergio Lupo, Leonardo Marianelli, Anabella Martin, Florencia M. Masciottra, Analía Mykietiuk, L. Orellano, Valeria Pachioli, María José Padilla, Cecilia Pallavicini, Jazmin Patroso, Luz Perez Blanco, José Presas, Matias Provenzano, Lorena Lavera, Viviana Reichert, F José Luis Riveros, Alejandra Rodríguez, María José Rolón, Carolina Salvay, María Simonetta, Alicia Sisto, Sandra Themines, Fernando Tito, Javier Toibaro, Graciela Torales, Luciano Verón, Carla Vizzotti, Alexander Egle, Richard Greil, Michael Joannidis, Antoine Altdorfer, Leïla Belkhir, Vincent Fraipont, Maya Hites, Érico Arruda, Giovanni Luís Breda, Arthur Colussi, Miran Corradi, Júlio Croda, Helena Duani, Esaú João, Elizabeth S. Machado, Fernanda Carvalho de Queiroz Mello, Demócrito Miranda Filho, Poliana Monteiro, Ceuci Nunes, Luiz Carlos Pereira, Gustavo Pinto, Sônia Mara Raboni, M. Á. Barón Ramos, Leonardo Ruffing, Valdilea Santos, Tamara Souza, Melissa Soares Medeiros, Alexandre Vargas Schwarzbold, Karim Ali, Tanweer Azher, David Bellemare, Alexandra Binnie, Sergio Borgia, Yiorgos Alexandros Cavayas, Nicholas Chagnon, Matthew P. Cheng, Eve Cloutier, John Conly, Cecilia T. Costiniuk, Nick Daneman, James Douglas, Catarina Downey, Erick Duan, Medeline Durand, Shane English, George Farjou, Evadiki Fera, Patricia Fontela, Rob Fowler, Mike Fralick, David Gregory Gamble, Anna Geagea, Jennifer Grant, Luke B. Harrison, Thomas Havey, Holly Hoang, Lauren E. Kelly, Yoav Keynan, Kosar Khwaja, Marina B. Klein, Christophe Kolan, Nadine Kronfli, François Lamontagne, Nelson Lee, Todd A. Lee, Rachel Lim, Alexandra Lostun, Erika MacIntyre, Isabelle Malhamé, Francois Martin-Carrier, Marlee McGuinty, Matthew Munan, Conar O’Neil, Daniel Ovakim, Jesse Papenburg, Ken Kuljit S. Parhar, Seema Nair Parvathy, Santiago Pérez-Patrigeón, Asgar Rishu, Moira Rushton, Kim Scherr, Kevin L. Schwartz, Makeda Semret, M Silverman, Ameeta E. Singh, Wendy Sligl, Stephanie Smith, Ranjani Somayaji, Darrell H. S. Tan, Tuong-Vi Tran, Alain Tremblay, Jennifer Tsang, Alexis F. Turgeon, Erik Vakil, Jason Weatherald, Cédric P. Yansouni, Ryan Zarychanski, Claudia Aristizabal, Juan Carlos Bravo, Monica Caicedo‐Roa, J. Mateos Chacon, Diego Garzón, Freddy Guevara, Silvia Lozano-Gonzàlez, Hugo Macareno, Anita Montañez-Ayala, José Oñate, Jose Rojas-Gambasica, Fernando Rosso, Carlos Saavedra, Sandra Valderrama, Eliana Vàquiro-Herrera, Fabio Varón-Vega, I.C. Guzmán Zuluaga, Amin Abdel Baki, Akram Abdelbary, Wael Abdel‐Razek, Wagdi Amin, Noha Asem, Gehan Elassal, Marwa Elshesheny, Mohamed Fathy, Naglaa Fathy, Notaila Fayed, Ahmed Hammam, Sahar M. Hassany, Hamdy Ibrahim, Ehab Kamal, Hossam Masoud, Maryam Mohamed, Abdullah Gouda, Ehab Moustafa, Shaimaa Okasha, Ahmed Rafik, Ahmad Said, Asmaa Sedky, Mohamed Solyman Kabil, Sara Tarek, A. Tharwat, Samy Zaky, Emawayish Tesema Abegaz, Zelalem Mekonnen Bekele, Filmona Mekuria Asfaw, Netsanet Aragaw Tegegne, Miheret Fikre Teklemariam, Frehiwot Nigusse, Daniel Legesse Achalu, Shewit Tesfagabr Weldegergs, Dawit Kebede Huluka, Addisu Birhanu Tereda, Tero Ala‐Kokko, Jutta Delany, Heikki Ekroos, Riina Hankkio, Mia Haukipää, Iivo Hetemäki, Pia Holma, Ville Holmberg, Saana Horstia, Ville Jalkanen, Toni Jämsänen, Juuso Järventie, Petrus Järvinen, Ilkka Kalliala, Heikki Kauma, Tuomas P. Kilpeläinen, Hanna‐Riikka Kreivi, Ilari Kuitunen, Satu Lamminmäki, Laura K. Mäkinen, Jarkko Mäntylä, Tiina Mattila, Marjukka Myllärniemi, Joni Niskanen, Taina Nykänen, Miro Nyqvist, Juuso Paajanen, Terhi Partanen, Riitta-Liisa Patovirta, Erja‐Leena Paukkeri, Emmi Puusti, Andreas Renner, Emma Reponen, Sari Risku, Tuomas Rosberg, Jarno Rutanen, Petrus Säilä, Päivi Salonen, Marjatta Sinisalo, Katariina Sivenius, Susanna Tuominen, Jerone Aboab, Toni Alfaiate, Claire Andréjak, Pascal Andreu, Drifa Belhadi, François Bénézit, Élisabeth Botelho-Nevers, Lila Bouadma, David Bougon, Kévin Bouiller, Fanny Vardon‐Bounes, Alexandre Boyer, Cédric Bruel, Alexandre Buffet, Charles Burdet, Charles Cazanave, Cyrille Chabertier, Rapahel Clere-Jehl, Dominique Costagliola, Johan-Victor Courjon, Flora Crockett, François Danion, Aline Dechanet, Jean Dellamonica, Christelle Delmas, Alpha Diallo, Félix Djossou, Clément Dubost, Axelle Dupont, Olivier Épaulard, Emmmanuel Faure, Karine Faure, Antoine Fayol, Samy Figueiredo, Claire Fougerou, Benjamin Gaborit, Rostane Gaci, Amandine Gagneux‐Brunon, Sébastien Gallien, Denis Garot, François Goehringer, Didier Gruson, O. Hinschberger, Jean‐Sébastien Hulot, S. Jauréguiberry, Vanessa Jean-Michel, Solen Kernéis, Antoine Kimmoun, Kada Klouche, Marie Lachâtre, Karine Lacombe, Fabrice Laine, Jean Philippe Lanoix, Samira Laribi, Odile Launay, Bruno Laviolle, Vincent Le Moing, Jérôme Le Pavec, David Lebeaux, Sylvie Leroy, X. Lescure, Marine Livrozet, Alain Makinson, Denis Malvy, Charles‐Hugo Marquette, Guillaume Martin‐Blondel, Julien Mayaux, Armand Mekontso Dessap, France Mentré, Noémie Mercier, Ferhat Meziani, Jean‐Michel Molina, Y. Mootien, Bruno Mourvillier, J C Navellou, Marion Noret, Nathan Peiffer‐Smadja, Gilles Peytavin, Gilles Pialoux, B. Pilmis, Lionel Piroth, Vincent Poindron, Julien Poissy, Valérie Pourcher, Jean‐Pierre Quenot, François Raffi, Jean Reignier, Jean Christoph Richard, Céline Robert, Juliette Saillard, N. Sayre, É. Senneville, Francois Stefan, Marie Capucine Tellier, Nicolas Terzi, Julien Textoris, Guillame Thiery, Jean François Timsit, Violaine Tolsma, Sarah Tubiana, Florent Wallet, Yazdan Yazdanpanah, Yoann Zerbib, Carlos A. Aguilar, Laura Erazo, Angel Fiallos, R. Figueroa, Juan José Flores, Lesddyy Melendez, Wendy Moncada, Ooriapadickal Cherian Abraham, Chetankumar Acharya, Vinaya Sekhar Aedula, Richa Aggarwal, Nishant Agrawal, Umang Agrawal, Abhishekh Agrawal, Mohammad Ahmad, Shubham Atal, Avinash Babu, Dalim Kumar Baidya, Amith Balachandran, Rakhee Bangar, Rakesh Bhadade, Sudhir Bhandari, Meghavi S Bhapal, Pankaj Bhardwaj, Gaurav Bhati, Pradeep Bhatia, Krishnakant Bhatt, Thrilok Chander Bingi, Rohidas Borse, Vyom Buch, Dipti Chand, Ashish Chandwani, Jaykaran Charan, Mayur Chaudhari, Kirti Chaudhari, Vipul Chaudhary, Nishant Kumar Chauhan, Gaurav Chikara, Bharti Daswani, Rosemarie de Souza, Chetna Desai, Balusamy Divakar, Sujeet A. 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Sathish Mohan, Mohmmedirfan Momin, Vijaya Lakshmi Nag, Ramakrishnan Nagarajan, Kammili Nagmani, Uday Narlawar, Gopalakrishnan Natarajan, Neeraj Nischal, Dhananjay Ogale, Paltial Palat, Prasan Kumar Panda, Samiran Panda, A. Pandya, Rohit Parate, Arunita Paritekar, Parvati B. Patel, Chetna Patel, Sunaina Patel, Vitan Patel, Deep Patel, Harshad Patel, Girish V. Patil, Deepu Peter, Durga Prasad, Vimlesh Purohit, Ebenezer Rabindrarajan, Lakshmiarasimhan Ranganathan, Tushara Rao, Chakradhara Rao, Chirag Rathod, Devang Raval, Avik Ray, Kamini Reddy, Sujata Rege, Ayyasamy Revathi, Dhara Roy, Saurabh Saigal, Suvarna Sane, Shashi Sangale, Krishnamoorthy Seetharaman, Poongulali Selvamuthu, K. V. Seshaiah, Benhur Joel Shadrach, Jignesh Shah, Sonal Shah, Swati Sharma, Raman Sharma, Shrikant Sharma, Krishna Kumar Singh, Anil Kumar Singh, Arjeet Singh, Abhishek Singhai, Manish Soneja, Kapil Dev Soni, Thasneem banu Subhan, Sudharshini Subramaniam, Thambu David Sudarsanam, Ravindra Kumar Sudarsi, Dawood Suleman, Nilay Suthar, Shriraj Talati, Murlidhar Tambe, Tilak Tejomurtula, B. Vijayaraghavan, Anjan Trikha, Aarti Trivedi, Zarir Udwadia, Kamlesh J. Upadhyay, Ashwin Vasava, Damodaran Vasudevan, Rajendran Velayudham, V Ramasubramanian, Mamta Verma, Rakesh Waghmare, Anushka K. 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Menatti, Maria Merelli, Esther Merlini, Caterina Monari, Angelo Pan, Davide Pecori, Diletta Pezzani, Niccolò Riccardi, Paola Rodari, Eugenia Quirós-Roldán, Pierangelo Rovere, Stefano Rusconi, Silvia Scabini, Carlo Tascini, Pierluigi Viale, Marcello Vincenzi, Paola Zuccalà, Patrizia Zucchi, Moudhi Alroomi, Salman Al‐Sabah, Kelly Schrapp, Mahmoud Hassoun, Madonna Matar, Oussaima El Dbouni, Nadine Yared, Michele Saliba, Anna Farra, Moussa Riachi, Birutė Zablockienė, Jean Reuter, Thérèse Staub, Suhaila Ab Wahab, Chun Keat Chew, Hock Hin Chua, Pik Pin Goh, Heng Gee Lee, Chee Loon Leong, Lee Lee Low, Wen Yao Mak, Yasmin Gani, Dzawani Muhamad, Nor Zaila Binti Zaidan, Camilla Ducker, Илир Демири, Saad Aballi, Åse Berg, Bjørn Blomberg, Olav Dalgård, Anne Ma Dyrhol‐Riise, Ragnhild Eiken, Gernot Ernst, Ranula Hannula, Metter Haugli, Lars Heggelund, Hedda Hoel, Dag Arne Lihaug Hoff, Aleksander Rygh Holten, Asgeir Johannessen, Trine Kåsine, Anders Benjamin Kildal, Bård Reikvam Kittang, Kateřina Nezvalová‐Henriksen, Inge Christoffer Olsen, Roy Bjørkolt Olsen, Nina Vibeche Skei, Hilde Skudal, Birgitte Tholin, Lars Thoresen, Marius Trøseid, Anders Tveita, Leif Erik Vinge, Carl Magnus Ystrøm, Issa Al Jahdhami, Khalid Al‐Naamani, Zakariya Al Balushi, Nenad Pandak, Salma Abbas, Nasim Akhtar, Sumeyya Azam, Dilshad Begum, Sadia Hassan, Fivzia Herekar, Shahzaib Khan, Ejaz Ahmad Khan, Syed Faisal Mahmood, Nosheen Nasir, Anum Rahim, Samreen Sarfaraz, Quratulain Shaikh, Faisal Sultan, Usman Walayat, Erika Cecilia Agurto-Lescano, Andrés Martín Alcántara-Díaz, Ana María Alva-Correa, José Gustavo Alvarado-Moreno, Bethsabé Ángeles-Padilla, Hugo César Arbañil-Huamàn, Pool Christopher Ávila-Reyes, Johan Azañero-Haro, Luis Barreto-Rocchetti, Jorge Marko A. Benitez-Peche, Karla Hortencia Bernal-Màlaga, Liliana Norma Cabrera-Portillo, Reynaldo Javier Carazas-Chavarry, Paloma M. Cárcamo, Indira Catalina Casimiro-Porras, Jhuliana Castillo-Espinoza, Jesús Norberto Chacaltana-Huarcaya, Carla Raquel Cornejo-Valdivia, Augusto Cruz-Chereque, Keith Cayetano Marcelino Del-Aguila-Torres, Erika Díaz-Chipana, Neil Flores Valdez, Rosanna Andrea Franco-Vàsquez, Roxana Consuelo Gallegos-López, Dauma Yesenia Gastiaburú-Rodriguez, Gonzalo Ernesto Gianella-Malca, Andrés Alonso Gomero-Lopez, Luis Enrique Hercilla-Vàsquez, Miguel Ángel Hueda-Zavaleta, Claudia Vanessa Ibárcena-Llerena, Carlos Alberto Iberico-Barrera, Miguel Angel Inquilla-Castillo, Jesus Alberto Juàrez-Eyzaguirre, Manuel Laca-Barrera, Franco León-Jiménez, Carla Vanessa Luna-Wilson, Germán Málaga, Ricardo Marin, Fernando Mejía, Juan Arturo Mendoza-Laredo, Edinson Dante Meregildo-Rodríguez, Gonzalo Miranda, Marco Olivera, Fatima Josefina Ortega-Monasterios, Jimmy Pedro Otazú-Ybàñez, María Angélica Paredes-Moreno, Claudia Ximena Peña-Mayorga, Olivia del Carmen Peña-Vàsquez, Alejandro Peña-Villalobos, Oscar J. Ponce, Katherin Estefania Ponte-Fernandez, Jose Pro, César Miguel Quispe-Nolazco, Manuel Efrain Ramos-Samanez, Kory Mirtha Rojas-Murrugarra, Jorge Mauro Samanez-Pérez, Halbert Chrostian Sànchez-Carrillo, Epifanio Sànchez-Garavito, Ricardo Manuel Sànchez-Sevillano, Hernan Sandoval-Manrique, Gabriela Santos-Revilla, Julio Antonio Silva-Ramos, Manuel Alberto Solano-Ico, Alonso Soto, Giannilu Michelle Sotomayor-Woolcott, Rubén Kevin Arnold Tapia-Orihuela, Carmen Sara Terrazas-Obregón, Victor Francisco Terrones-Levano, César Ticona Huaroto, Walter Torres-Ninapayta, Oscar Martin Torres-Ruiz, Dario Ugarte-Mercado, Orlando José Vargas-Anahua, Ruben Dario Vàsquez-Becerra, José Gabriel Vàsquez-Cerro, Miguel Villegas-Chiroque, Anna Larson Williams, Randi Mauricio Yauri-Lazo, Cybéle Lara R. Abad, Silverose Ann Andales-Bacolcol, Marlon Arcegono, Jamie Arches, Mary Grace Astudillo, Emily Aventura, Arlyn Gaballo Awing, Mishelle Vonnabie Bala, Jia An Bello, Peter Blanco, Jubert Benedicto, Susana Buno, J.A. Blázquez Cabrera, Thea Pamela Cajulao, Janice Caoili, Lina Casiple-Amsua, Victor Catambing, Inofel Chin, Matthew Hendric Chua, Mitzi Marie Chua, Fresthel Monica M. Climacosa, Aileen David-Wang, Virginia De los Reyes, Gilly May Europa, Lenora Fernandez, Jorge Francisco, Gerard Garcia, Jemelyn Garcia, Maria Tarcela Gler, Marie Grace Dawn Isidro, Rozelle Jade Javier, Marion Kwek, Mary Ann Lansang, Aileen Lee, Kingbherly Li, Mark Ramon Victor Llanes, Ryan Llorin, Omar Khayyam Macadato, Anna Flor G. Malundo, Maria Elizabeth Mercado, Mercedes Mujeres, Marisse Nepomuceno, Katha Ngo-Sanchez, MARY CLAIRE R. ORDEN, Maria Philina Pablo-Villamor, Ruel Dionisio Paez, Patricio Palmes, Marion Panaligan, Jenny Mae Quinivista-Yoon, Mary Shiela Ariola Ramos, Christine Penalosa, Sheila Marie Reyes, Kathryn Roa, Arthur Dessi Roman, Minette Claire Rosario, Evalyn A. Roxas, Lourdes Ella Gonzales Santos, Helmar Soldevilla, Rontgene Solante, Jane Suaco, Daisy Tagarda, Issa Rufina Tang, Bob Te, Dennis Teo, Christopher John Tibayan, Ralph Elvi Villalobos, Duane Richard Ymbong, Gelza Mae A Zabat, Fresthel Monica M. Climacosa, Maria Elizabeth Mercado, Maria Philina Pablo-Villamor, Stepanka Batkova, Orlando Cardoso, Ana-Raquel Garrote, Sara Lino, M. J. Manata, Hélder Pinheiro, Diana Póvoas, Freddy Ramírez, Diana Seixas, Assem Naji, M Al Al Gethamy, Mohammed S. Almulaify, Reem Al Maghraby, Abdulrahman A. Alrajhi, Aynaa Al Sharidi, Naif H. Alotaibi, F AlShaharani, Mazin Barry, Leen Ghonem, Anas Khalel, Ayman Kharaba, Lulwah Alabdan, Mohammed Sharaf AlAbdullah, Abdullah Al Shabib, Simangele Bengu, Josh Bennet, Thozama Dubula, Pauline Howell, Cloete Janse van Vuuren, Ismail Kalla, Aimee Lifson, Shaun Maasdorp, Nombulelo Magua, Vongani Maluleke, Nokuphiwa Mbhele, Nathi Mdladla, Mark Mendelson, Colin Menezes, Thando Mwelase, Maphoshane Nchabeleng, Thesla Palanee‐Phillips, Victoria A. Parker, Mohammed Rassool, P S REEDER, Bianca Sossen, Dewald Steyn, Merika Tsitsi, Sarah Alex van Blydenstein, Michelle Venter, Janse Van Vuuren, Jacquie Venturas, Daniel Abad Pérez, María José Abenza, Carolina Alarcón-Payer, Eva Garrigós, José Ramón Arribas, Ana Ascaso, Juan Berenguer, Noemí Cabello‐Clotet, Sandra Chamorro Tojeiro, Rafael Cuenca-Acevedo, Fernando Calle, Maria Dolores Del Toro, Beatriz Díaz Pollàn, Cristina Díez, M. José Esquillor-Rodrigo, Vicente Estrada, Chiara Fanciulli, Francisco Fanjul, Lucía Fernández de Orueta, Adrian Ferre, Eva María Ferreira Pasos, Juan-Carlos Gainzarain-Arana, Felipe García, Miguel García Deltoro, Ane Josune Goikoetxea Agirre, Julia Gómez Barquero, Ricardo Gómez-Huelgas, Julio González Moraleja, Carlos Guijarro, Félix Gutiérrez, Jesús Guzmàn, Maialen Ibarguren, José Antonio Iribarren, Koen Jerusalem, A.J. Arribas, Antonio Lalueza, Antonio Maria Leone, Iñigo López Azkarreta, Daniel Lozano-Martin, Alfredo J. Lucendo, Mariella Luengo López, JA Martín Oterino, J. F. Masa, Esperanza Merino, Begoña Monge‐Maíllo, Miguel Ángel Morán Rodríguez, Elena Muñez Rubio, Josefa Muñoz Sánchez, María José Núñez Orantos, Enrique Nuño, Zuriñe Ortiz-de-Zárate-Ibarra, B. Pagán-Muñoz, José Ramón Paño‐Pardo, María Luz Pintos Peñaranda, Gerardo Pérez Chica, AM Pérez Fernàndez, Carmen Pérez-López, Victor Polo San Ricardo, Joseba Portu-Zapirain, Francesco Puchades, A. Paterna, Francisco Félix Rodríguez Vidigal, Jesús Rodríguez‐Baño, Pilar Ruíz-Seco, Pablo Ryan, Ester Saez-De-Adana, Rosario Salas, Miguel Salavert Lletí, Raquel Sandoval, Carla Toyas-Miazza, Jorge Valencia, Emilio Vargas, María Velasco, Miguel Ángel von Wichmann, Andreas Bosshard, Alexandra Calmy, Tiago Castro, Matthias Cavassini, Olivier Clerc, Anna Conen, Nicolas Desbaillets, Florian Desgranges, Francois Duss, Stéphane Emonet, Véronique Erard, Myriam M. Eyer, Aurélie Fayet-Mello, Yvonne Flammer, Andrée Friedl, Rosamaria Fulchini, Hansjakob Furrer, Nicolas Garin, Salome Gastberger, Michael Greiner, David Haefliger, Sebastian Haubitz, Matthias Hoffmann, Egon Isenring, Barbara Jakopp, Markus L. Lampert, Annalisa Marinosci, Yvonne Martin, Pierre‐Auguste Petignat, Rein Jan Piso, Virginie Prendki, Jonas Rutishauser, Elisabeth Schaefer, Yvonne Schmiedel, Stefan Schwery, Elisavet Stavropoulou, Marcel Stoeckle, Véronique Suttels, Maria Christine Thurnher, Lorena van den Bogaart, Emily West, Jan Wiegand, Benedikt Wiggli - The Lancet 2022 被引用: 403

BACKGROUND: The Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-β1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date. METHODS: Solidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-β1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948. FINDINGS: Between March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82-1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89-1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76-0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46-1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76-0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77-1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75-0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings. INTERPRETATION: Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both). FUNDING: WHO.