1. Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial
- Author
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Labro, Guylaine, Tubach, Florence, Belin, Lisa, Dubost, Jean-Louis, Osman, David, Muller, Grégoire, Quenot, Jean-Pierre, da Silva, Daniel, Zarka, Jonathan, Turpin, Matthieu, Mayaux, Julien, Lamer, Christian, Doyen, Denis, Chevrel, Guillaume, Plantefeve, Gaétan, Demeret, Sophie, Piton, Gaël, Manzon, Cyril, Ochin, Evelina, Gaillard, Raphael, Dautzenberg, Bertrand, Baldacini, Mathieu, Lebbah, Said, Miyara, Makoto, Pineton de Chambrun, Marc, Amoura, Zahir, Combes, Alain, Palmyre, Jessica, Gimeno, Linda, Kone, Assitan, Vialette, Cedric, Slimi, Ouramdane, Chommeloux, Juliette, Lefevre, Lucie, Schmidt, Matthieu, Hekimian, Guillaume, Luyt, Charles-Edouard, Stiel, Laure, Dureau, Anne-Florence, Khaldoun, Kuteifan, Eid, Hanna, Baldacini, Matthieu, Zyberfajn, Cecile, Manson, Julien, Charrier, Nathanael, Balabanian, Angelique, Contou, Damien, Pajot, Olivier, Fraisse, Megan, Desaint, Paul, Sarfati, Florence, Fartoukh, Muriel, Voirot, Guillaume, Elabbabi, Alexandre, Djibre, Michel, Desnos, Cyrielle, Garcon, Pierre, van Vong, Ly, Issad, Andrea, Pillot, Bertrand, Reither, Delphine, Rouge, Patrick, Foliot, Pascale, Bendjamar, Lynda, Pointurier, Valentin, Winiszewski, Hadrien, Capellier, Gilles, Navellou, Jean-Christophe, Tapponnier, Romain, Panicucci, Emilie, Morand, Lucas, Dellamonica, Jean, Saccheri, Clement, Weiss, Nicolas, Marois, Clemence, Le Guennec, Loic, Rohaut, Benjamin, Ensenat, Luis, Billiou, Cecilia, Aroca, Maria, Baron, Marie, Demoule, Alexandre, Beurton, Alexandra, Bureau, Come, Decavele, Maxens, Dres, Martin, Bayle, Frederique, Le, Quoc Viet, Liron, Lionel, Putegnat, Jean-Baptiste, Salord, Francois, Andreu, Pascal, Slimani, Hakim, Roudeau, Baptiste, Labruyere, Marie, Jacquier, Marine, Anguel, Nadia, Ayed, Soufia, Durand, Edgard, Guerin, Laurent, Lai, Christopher, Aboab, Jerome, Alviset, Sophie, Laine, Laurent, Azzi, Mathilde, Issoufaly, Tazime, Tric, Laurent, Knani, Lyes, Boumezrag, Chahrazad Bey, Viault, Nicolas, Barbier, Francois, Boulain, Thierry, Kamel, Toufik, Nay, Mai-Anh, Tollec, Sophie, Nguyen, an Hung, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Département de santé publique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier René Dubos - 6, avenue de l’Ile de France 95303 CERGY-PONTOISE, Service de Pneumologie et Réanimation Respiratoire [AP-HP Hôpital Bicêtre] (DHU TORINO), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Centre de Référence de l'Hypertension Pulmonaire Sévère, Centre Hospitalier Régional d'Orléans (CHRO), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), réanimation et soins continus [CH Saint-Denis], Centre Hospitalier de Saint-Denis [Ile-de-France], Grand Hôpital de l'Est Francilien (GHEF), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département Médico-Universitaire APPROCHES, Sorbonne Université (SU), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut Mutualiste de Montsouris (IMM), Hôpital l'Archet, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Sud Francilien, Centre Hospitalier Victor Dupouy, REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aigüE [CHU Pitié-Salpêtrière] (GRC RESPIRE), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Réanimation, Médipole Lyon Villeurbanne. Service de réanimation. 158 rue Léon Blum. 69100 VILLEURBANNE, France, Service de médecine intensive-réanimation Hôpital Simone Veil, Eaubonne, France, GHU Paris Psychiatrie et Neurosciences, Université Paris Cité (UPCité), Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), Institut Arthur Vernes, Unité de Recherche Clinique des hôpitaux Pitié-Salpêtrière – Charles Foix [CHU Pitié Salpêtrière] (URC PSL-CFX), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Service de Réanimation Médicale [CHU Pitié-Salpétrière], and TUBACH, Florence
- Subjects
Adult ,Male ,Nicotine ,[SDV]Life Sciences [q-bio] ,Acute respiratory failure ,Critical Care and Intensive Care Medicine ,MESH: Nicotine ,Nicotinic receptor ,Double-Blind Method ,MESH: COVID-19 ,Humans ,MESH: SARS-CoV-2 ,MESH: Double-Blind Method ,MESH: Respiration, Artificial ,MESH: Treatment Outcome ,MESH: Humans ,SARS-CoV-2 ,COVID-19 ,MESH: Adult ,Respiration, Artificial ,Ventilation ,MESH: Male ,[SDV] Life Sciences [q-bio] ,Intensive Care Units ,Treatment Outcome ,Artificial ,MESH: Intensive Care Units ,Female ,Randomized trial ,MESH: Female - Abstract
Epidemiologic studies have documented lower rates of active smokers compared to former or non-smokers in symptomatic patients affected by coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of nicotine administered by a transdermal patch in critically ill patients with COVID-19 pneumonia.In this multicentre, double-blind, placebo-controlled trial conducted in 18 intensive care units in France, we randomly assigned adult patients (non-smokers, non-vapers or who had quit smoking/vaping for at least 12 months) with proven COVID-19 pneumonia receiving invasive mechanical ventilation for up to 72 h to receive transdermal patches containing either nicotine at a daily dose of 14 mg or placebo until 48 h following successful weaning from mechanical ventilation or for a maximum of 30 days, followed by 3-week dose tapering by 3.5 mg per week. Randomization was stratified by centre, non- or former smoker status and Sequential Organ Function Assessment score ( or ≥ 7). The primary outcome was day-28 mortality. Main prespecified secondary outcomes included 60-day mortality, time to successful extubation, days alive and free from mechanical ventilation, renal replacement therapy, vasopressor support or organ failure at day 28.Between November 6th 2020, and April 2nd 2021, 220 patients were randomized from 18 active recruiting centers. After excluding 2 patients who withdrew consent, 218 patients (152 [70%] men) were included in the analysis: 106 patients to the nicotine group and 112 to the placebo group. Day-28 mortality did not differ between the two groups (30 [28%] of 106 patients in the nicotine group vs 31 [28%] of 112 patients in the placebo group; odds ratio 1.03 [95% confidence interval, CI 0.57-1.87]; p = 0.46). The median number of day-28 ventilator-free days was 0 (IQR 0-14) in the nicotine group and 0 (0-13) in the placebo group (with a difference estimate between the medians of 0 [95% CI -3-7]). Adverse events likely related to nicotine were rare (3%) and similar between the two groups.In patients having developed severe COVID-19 pneumonia requiring invasive mechanical ventilation, transdermal nicotine did not significantly reduce day-28 mortality. There is no indication to use nicotine in this situation.
- Published
- 2022
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