1. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial
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Anatole Harrois, Florence Patin, Anaïs Razurel, Laure Allanic, Grégoire Martin de Frémont, Vincent Jachiet, Gonçalo Boleto, Eric D'Ortenzio, Xavier Mariette, Philippe Dieudé, Etienne Canouï, Z Julia, Nathalie Dournon, Jean-Sébastien Hulot, David Lebeaux, Eric Mariotte, Dorothee Vallois, Laurence Berard, Nicolas Gambier, Christiane Verny, Mathilde Le Marchand, Mitja Jevnikar, Jean-Jacques Mourad, Marjolaine Morgand, Bertrand Guidet, Alexandre Moores, Prissile Bakouboula, Frédéric Pène, Pascal Richette, Martine Meunier, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Mamadou Salif Cisse, Marie-Hélène Legros, Yann Nguyen, Damien Roux, Robin Deleris, Maxence Decavele, Patrice Cacoub, Isabelle Dusanter, Patricia Senet, Nassim Mahtal, Raphael Borie, Philippe Benoit, Blandine Denis, Luca Semerano, Sebastien Abad, Marie Dubert, Marie Lachatre, Marine Livrozet, Nathan Ebstein, Lakhdar Mameri, Adrien Michon, Olivier Sanchez, Aurélien Guffroy, Pierre Dupland, Jérôme Pacanowski, Yasmina Ferfar, Tassadit Hadjam, Anne-Marie Roques, Celine Comparon, Solaya Chalal, A Soria, Isabelle Lehir, Anne Gysembergh-Houal, Stéphanie Alary, Valérie Dejean, Elena Kiouris, Estelle Henry, Sophie Diemunsch, Jonathan London, Fanny Charbonnier, Alexandre Demoule, Louise Bondeelle, Samira Saleh-Mghir, Lise Bernard, Brigitte Sabatier, Anne Jacolot, Aurelie Sautereau, Pierre Faye, Benjamin Fournier, Noémie Abisror, Awa Ndiaye, Ruben Benainous, Damien Sène, Emmanuelle Sacco, Isabelle Debrix, Gabriel Nisand, Régis Peffault de Latour, Anne Sophie Korganow, Kévin Cardet, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Elena Fois, Jean-Benoit Arlet, Christine Broissand, Yaël Amara, Matheus Vieira, Sophie Caillat-Zucman, Madona Sakkal, Juliette Djadi-Prat, Jean-Louis Teboul, Hélène François, Stéphane Renaud, Sylviane Ravato, Alaki Thiemele, Gabrielle Archer, Alain Fourreau, David Boutboul, Arsène Mekinian, Antoine Gros, Morgane Faure, Anne Pattyn, Camille Petit-Hoang, Jessica Krause le Garrec, Antony Canellas, Jean-Michel Molina, Zakaria Ait Hamou, Eric Oksenhendler, Ilias Koumis, Marie-Aude Penet, Catherine Boussard, Vincent Fallet, Guillaume Geri, Loic Kassegne, Bernard Cholley, Lucie Biard, Elodie Perrodeau, Tomas Urbina, David Schmitz, johann Cailhol, Elise Morawiec, Audrey Phibel, Sophie Renet, Emmanuel Weiss, Faouzi Saliba, Kristina Beziriganyan, Abdellatif Tazi, Isabelle Peigney, Bertrand Dunogue, Rémy Gauzit, Damien Bergerot, Bob Heger, Ines Ben-Mabrouk, Jade Ghosn, Benjamin Planquette, Alexis Régent, François Weill, Yasmina Mekid, Rosa Da Silva, Victor Lancon, Marc Michel, Nadia Anguel, Anne Claire Desbois, François Danion, Brigitte Ranque, Mohamed Belloul, Nadège Lemarié, Amélie Cransac, Marine Nadal, Lalia Djaghout, Anne Tréhan, Samy Figueiredo, Hakim Meddah, Aurélie Clan Hew Wai, Julie Delemazure, Soraya Fellahi, Jacques-Eric Gottenberg, Matthieu Uzzan, Jean-Charles Duclos-Vallée, Tabassome Simon, Vanessa Rathouin, Yves Hansmann, Hélène Gros, Syllia Belazouz, Nathalie Marin, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Annabelle Stoclin, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Miguel Alejandro Vasquez-Ibarra, Isabelle Madeleine, Simon Valayer, Anne Adda, Marie-Thérèse Tremorin, Nicolas Meyer, Vixra Keo, Lara Zafrani, Caroline Semaille, Maxime Dougados, Olivier Olivier, Emeline Colomba, Florence Morin, Claire Rouzaud, Paul Michel Mertes, Claire Montlahuc, Anne Blanchard, Valérie Pourchet-Martinez, Constance Delaugerre, Nicolas Carlier, Jacques Cadranel, Nicolas Noel, Kahina Cheref, Bao Phung, Moez Jallouli, Ulrich Clarac, Marthe Rigal, Mireille Adda, Lionel Galicier, Fanny Domont, Lee S. Nguyen, Férial Berbour, Fanny Pommeret, Celine Dupré, Gaël Leprun, Jean-Luc Diehl, Laetitia Languille, Philippe Blanche, Abolfazl Mohebbi, Mathilde Noaillon, Olivier Collange, Paul Jaubert, Anne Daguenel-Nguyen, Sandrine Briois, Anne-Lise Pouliquen, Coralie Bloch Queyrat, Clément Jourdaine, Cédric Pierron, Geoffrey Rossi, Chloe McAvoy, Claire Courtin, Mathias Cornic, C Rioux, Christine Lemagner, Martin Dres, Emmanuelle Guillot, Marc Garnier, Safaa Nemlaghi, Guillaume Grailles, Yazdan Yazdanpanah, Veronique Joly, Thiziri Sadaoui, Marion Bouhris, Vincent Castelain, Muriel Fartoukh, Sébastien Cavelot, Sophie Ohlmann-Caillard, Valentina Isernia, Bruno Crestani, Thinhinane Bariz, Benjamin Chaigne, Emmanuel Andrès, Frédéric Blanc, Alain Wynckel, Louise-Laure Mariani, Yasmine Messaoudi, Naima Sguiouar, Amina Kebir, Asmaa Mamoune, Caroline Gaudefroy, Victoire De Lastours, Pierre Diemunsch, Etienne Lengliné, Claire Tantet, Julien Mayaux, Benjamin G. Chousterman, Arthur Pavot, Anne Rachline, Gwenaël Lorillon, Hassan Joumaa, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Fanny Defrancq, Véronique Vigna, Yves Cohen, Amira Benattia, Martin Siguier, Sophie Georgin-Lavialle, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Olivier Hermine, Mathieu Vautier, Florence Tubach, Marion Licois, Anaïs Codorniu, Fanny Alby-Laurent, Jérémie Zerbit, Aude Jacob, Benedicte Giroux-Leprieur, Carine Karachi, Laurent Cylly, Edouard Flamarion, Gladys Aratus, Charléne Jouve, Robin Dhote, Claire Davoine, Valentin Greigert, Gaelle Leroux, Cécile Kedzia, Guillaume Lefèvre, Catherine Metzger, Olivier Benveniste, Clairelyne Dupin, Marie-Alexandra Alyanakian, Mathieu Oberlin, Julien Poissy, Linda Gimeno, Adrien Contejean, Segolene Toquet, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Virginie Zarrouk, Cécile Yelnik, Mandy Nizard, Mourad Djadel, F-Xavier Lescure, Agnes Maurer, Geoffroy Liégeon, Arthur Neuschwander, Hélène Lafoeste, Gaëtan Deslée, Frédéric De Blay, Claire Pernin, Cloé Comarmond, Anne Hutt, Ridha Belilita, Laurence Lecomte, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Jean-Jacques Tudesq, Benjamin Terrier, Solène Fabre, Lelia Escaut, Eva Chatron, Emmanuelle Blin, Pauline Jouany, Sara Sambin, Chistophe Willekens, Nabil Raked, Jean-Simon Rech, Serge Bureau, Boris Bienvenu, Elisabeth Coupez, Tali-Anne Szwebel, Lydia Suarez, Chaouki Bouras, Kamyl Baghli, Emilia Stan, Valérie Camara-Clayette, Fanette Denies, Nathalie Menage, Paul Legendre, Axelle Fuentes, Oriane Puéchal, Charlotte Kaeuffer, Guillaume Becker, Clara Campos-Vega, Armand Mekontso-Dessaps, Pernelle Vauboin, Yurdagul Uzunhan, F Louni, Marie hélène Pari, Myriam Virlouvet, Nicolas Belaube, Hugues Cordel, Nathalie Chavarot, Olivier Sitbon, Jean-Daniel Lelievre, Matthieu Mahévas, Julie Smati, Olivier Clovet, Marc Bardou, Ada Clarke, Gilles Garcia, Anouk Walter-Petrich, Hala Semri, Vasco Honsel, Giovanna Melica, Pierre Mora, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Céline Verstuyft Verstuyft, Blandine Lehmann, Pascal Martel, Aida Zahrate-Ghoul, Karine Martin, Alexandre Bourgoin, Baptiste Duceau, Philippe Ravaud, Celine Wilpotte, Sylvie Le Gac, Michaël Darmont, Aurélie Durel Maurisse, Younes Keroumi, Aude Rigolet, Julie Chas, Pierre-Louis Tharaux, Caroline Morbieu, Valérie Paquet, Eric Vicaut, Pascaline Choinier, Samir Hamiria, Elsa Feredj, Frédéric Schlemmer, Gilles Pialoux, Zeina Louis, Marion Parisey, David Montani, Jean-Pierre Riveline, Jean-Marie Michot, Pascal Lim, Eliane Bertrand, Gaelle Clavere, Julie Jambon, Stéphane Brin, Saskia Flamand, Jeanne Meunier, Geoffroy Volle, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Caroline Hauw-Berlemont, Gabriel Baron, Jeremy Arzoine, Loren Soyez-Herkert, Maria Pereira, Antoine Parrot, Johanna Oziel, Carole Burger, Eric Noll, Paul Vermes, Jeanne Goupil de Bouille, Xavier Monnet, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Jean-Philippe Bastard, Younes El Amine, Timothee Bironne, Damien Vanhoye, Amine Ghembaza, Laure Berton, Yvon Ruch, Thomas Volpe, Thomas Gorget, Jaouad Benhida, Julien Saussereau, Elodie Issorat, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Laurène Deconinck, A. Dossier, Félix Ackermann, Greggory Ducrocq, Anne Bergeron, Laurence Annonay, Camille Knosp, Laurence Drouard, Adrien Joseph, Hilario Nunes, Hanane Fodil, Sabrine Ouamri, Belkacem Asselate, Julie Fillon, Dominique Dautel, Isabelle Brindele, Robin Charreteur, S Lariven, Elie Azoulay, Sami Kolta, Cédric Sublon, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Bruno Mourvillier, Ewa Kozaliewicz, Vincent Provitolo, Marie Lecronier, Julien Chabert, Matthieu Resche-Rigon, Stéphan Pavy, Naura Gamany, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Corinne Guerin, Pierre Tissieres, Nathalie Costedoat-Chalumeau, Nessima Yelles, Emmanuel Chatelus, Jean-Christophe Corvol, Luc Mouthon, Marie Gilbert, Matthieu Lemoine, Lucie Aunay, Candice Estellat, Laure Choupeaux, Dhiaa Meriem Hai, Bernard Goichot, Céline Louapre, Roza Rahli, Nathalie De Castro, Christian Richard, Malikhone Chansombat, Kamil Chitour, Joseph Emmerich, Elodie Drouet, Julien Pottecher, Eric Demonsant, Alexandra Beurton, Raphaël Porcher, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Pierre-Grégoire Guinot, Nicolas Champtiaux, Caroline Pradon, Annick Tibi, Julien Le Marec, Nawal Derridj, Mohamad Zaidan, Eric Marquis, Mickael Henriques, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Diane Le Pluart, Coralie Gernez, Yacine Boudali, Dimitri Fremont, Pierrick Le Borgne, Corinne Pernot, Mélanie Dehais, Claire Madelaine, Dominique Roulot, Georgina Maalouf, Constance Guillaud, Corine Nyanou, Karine Celli Lebras, Sophie Granville, Sabrina Brahmi, Catherine Le Bourlout, Hassan Tarhini, Asmaa Mabrouki, Hakim Tayebi, Sophie Ismael, Jonathan Marey, Sophie Bayer, Gabriel Steg, Antoine Fayol, Catherine Fauvaux, Delphine Feyeux, Côme Bureau, Alexandre Morel, Agathe Bounhiol, Alexandre Buffet, Souad Benarab, Luc Haudebourg, Pierre Le Guen, Damien Vimpere, Xavier Jaïs, Clotilde Le Tiec Le Tiec, Sophie Bulifon, Pélagie Thibaut, Alison Klasen, Claire Pacheco, Anne Godier, Marie Antignac, Domitille Molinari, Philippe Durand, Olivier Lambotte, Paul Henri Grisot, Anne Lise Jegu, Vincent Poindron, Ruxandra Burlacu, Denis Jesuthasan, Sarah Benghanem, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Sara Virolle, Léa Resmini, Liem Binh Luong Nguyen, Marie Matignon, Céline Leplay, and Claire Aguilar
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medicine.medical_specialty ,business.industry ,Immunology ,Hazard ratio ,Absolute risk reduction ,Articles ,medicine.disease ,law.invention ,Clinical trial ,Pneumonia ,Sarilumab ,Rheumatology ,Randomized controlled trial ,law ,Internal medicine ,Cohort ,medicine ,Immunology and Allergy ,Adverse effect ,business - Abstract
Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris
- Published
- 2022