1. Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single-blind, randomised controlled trial
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Jean-Michel Constantin, Matthieu Jabaudon, Jean-Yves Lefrant, Samir Jaber, Jean-Pierre Quenot, Olivier Langeron, Martine Ferrandière, Fabien Grelon, Philippe Seguin, Carole Ichai, Benoit Veber, Bertrand Souweine, Thomas Uberti, Sigismond Lasocki, François Legay, Marc Leone, Nathanael Eisenmann, Claire Dahyot-Fizelier, Hervé Dupont, Karim Asehnoune, Achille Sossou, Gérald Chanques, Laurent Muller, Jean-Etienne Bazin, Antoine Monsel, Lucile Borao, Jean-Marc Garcier, Jean-Jacques Rouby, Bruno Pereira, Emmanuel Futier, Cayot Sophie, Godet Thomas, Guerin Renaud, Verlac Camille, Chabanne Russel, Cosserant Bernard, Blondonnet Raiko, Lautrette Alexandre, Eisenmann Nathanael, Muller Laurent, Massanet Pablo, Boutin Caroline, Barbar Saber, Roger Claire, Belafia Fouad, Cisse Moussa, Monnin Marion, Conseil Matthieu, Carr Julie, De Jong Audrey, Dargent Auguste, Andreu Pascal, Lebouvrier Thomas, Launey Yoann, Roquilly Antoine, Cinotti Raphael, Tellier Anne-Charlotte, Barbaz Mathilde, Cohen Benjamin, Lemarche Edouard, Bertrand Pierre-Marie, Arberlot Charlotte, Zieleskiewicz Laurent, Hammad Emmanuelle, Duclos Garry, Mathie Calypso, Dupont Herve, Veber Benoit, Orban Jean-Christophe, Quintard Hervé, Rimmele Thomas, Crozon-Clauzel Julien, Le Core Marinne, Grelon Fabien, Assefi Mona, Petitas Frank, Morel Jerome, Molliex Serge, Hadanou Nanadougmar, CHU Clermont-Ferrand, Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Le Mans (CH Le Mans), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital St Roch, Département d'anesthésie-Réanimation-Samu, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Edouard Herriot Hospital, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU de Saint-Brieuc, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Department of Anesthesiology and Critical Care Medicine, Emile-Roux general hospital, Le Puy-en-Velay, Université de Montpellier (UM), Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Department of Perioperative Medicine, CHU Clermont-Ferrand, CHU Pitié-Salpêtrière [APHP], Hopital Général, Le Mans, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Hospital General Saint-Brieuc, Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Centre Régional de Lutte Contre le Cancer Jean Perrin, Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Service de réanimation adulte, département d'anesthésie-réanimation, CHU Clermont-Ferrand-Hôtel Dieu, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), University Hospital of Clermont-Ferrand, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Unité de biostatistiques, CHU Clermont-Ferrand-Hôpital Montpied, Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), MORNET, Dominique, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
- Subjects
Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,ARDS ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,law.invention ,Positive-Pressure Respiration ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Fraction of inspired oxygen ,Intensive care ,medicine ,Prone Position ,Tidal Volume ,Humans ,Single-Blind Method ,030212 general & internal medicine ,Prospective Studies ,Precision Medicine ,Lung ,Positive end-expiratory pressure ,Tidal volume ,ComputingMilieux_MISCELLANEOUS ,Proportional Hazards Models ,Mechanical ventilation ,Respiratory Distress Syndrome ,business.industry ,Hazard ratio ,Middle Aged ,medicine.disease ,Respiration, Artificial ,3. Good health ,[SDV] Life Sciences [q-bio] ,Intensive Care Units ,Editorial Commentary ,Treatment Outcome ,030228 respiratory system ,Female ,France ,business - Abstract
The effect of personalised mechanical ventilation on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remains uncertain and needs to be evaluated. We aimed to test whether a mechanical ventilation strategy that was personalised to individual patients' lung morphology would improve the survival of patients with ARDS when compared with standard of care.We designed a multicentre, single-blind, stratified, parallel-group, randomised controlled trial enrolling patients with moderate-to-severe ARDS in 20 university or non-university intensive care units in France. Patients older than 18 years with early ARDS for less than 12 h were randomly assigned (1:1) to either the control group or the personalised group using a minimisation algorithm and stratified according to the study site, lung morphology, and duration of mechanical ventilation. Only the patients were masked to allocation. In the control group, patients received a tidal volume of 6 mL/kg per predicted bodyweight and positive end-expiratory pressure (PEEP) was selected according to a low PEEP and fraction of inspired oxygen table, and early prone position was encouraged. In the personalised group, the treatment approach was based on lung morphology; patients with focal ARDS received a tidal volume of 8 mL/kg, low PEEP, and prone position. Patients with non-focal ARDS received a tidal volume of 6 mL/kg, along with recruitment manoeuvres and high PEEP. The primary outcome was 90-day mortality as established by intention-to-treat analysis. This study is registered online with ClinicalTrials.gov, NCT02149589.From June 12, 2014, to Feb 2, 2017, 420 patients were randomly assigned to treatment. 11 patients were excluded in the personalised group and nine patients were excluded in the control group; 196 patients in the personalised group and 204 in the control group were included in the analysis. In a multivariate analysis, there was no difference in 90-day mortality between the group treated with personalised ventilation and the control group in the intention-to-treat analysis (hazard ratio [HR] 1·01; 95% CI 0·61-1·66; p=0·98). However, misclassification of patients as having focal or non-focal ARDS by the investigators was observed in 85 (21%) of 400 patients. We found a significant interaction between misclassification and randomised group allocation with respect to the primary outcome (p0·001). In the subgroup analysis, the 90-day mortality of the misclassified patients was higher in the personalised group (26 [65%] of 40 patients) than in the control group (18 [32%] of 57 patients; HR 2·8; 95% CI 1·5-5·1; p=0·012.Personalisation of mechanical ventilation did not decrease mortality in patients with ARDS, possibly because of the misclassification of 21% of patients. A ventilator strategy misaligned with lung morphology substantially increases mortality. Whether improvement in ARDS phenotyping can decrease mortality should be assessed in a future clinical trial.French Ministry of Health (Programme Hospitalier de Recherche Clinique InterRégional 2013).
- Published
- 2019
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