Intensive Care Medicine

, Volume 45, Issue 5, pp 592–600 | Cite as

Feasibility and safety of extracorporeal CO2 removal to enhance protective ventilation in acute respiratory distress syndrome: the SUPERNOVA study

  • Alain Combes
  • Vito Fanelli
  • Tai Pham
  • V. Marco RanieriEmail author
  • On behalf of the European Society of Intensive Care Medicine Trials Group and the “Strategy of Ultra-Protective lung ventilation with Extracorporeal CO2 Removal for New-Onset moderate to severe ARDS” (SUPERNOVA) investigators
Seven-Day Profile Publication



We assessed feasibility and safety of extracorporeal carbon dioxide removal (ECCO2R) to facilitate ultra-protective ventilation (VT 4 mL/kg and PPLAT ≤ 25 cmH2O) in patients with moderate acute respiratory distress syndrome (ARDS).


Prospective multicenter international phase 2 study. Primary endpoint was the proportion of patients achieving ultra-protective ventilation with PaCO2 not increasing more than 20% from baseline, and arterial pH > 7.30. Severe adverse events (SAE) and ECCO2R-related adverse events (ECCO2R-AE) were reported to an independent data and safety monitoring board. We used lower CO2 extraction and higher CO2 extraction devices (membrane lung cross-sectional area 0.59 vs. 1.30 m2; flow 300–500 mL/min vs. 800–1000 mL/min, respectively).


Ninety-five patients were enrolled. The proportion of patients who achieved ultra-protective settings by 8 h and 24 h was 78% (74 out of 95 patients; 95% confidence interval 68–89%) and 82% (78 out of 95 patients; 95% confidence interval 76–88%), respectively. ECCO2R was maintained for 5 [3–8] days. Six SAEs were reported; two of them were attributed to ECCO2R (brain hemorrhage and pneumothorax). ECCO2R-AEs were reported in 39% of the patients. A total of 69 patients (73%) were alive at day 28. Fifty-nine patients (62%) were alive at hospital discharge.


Use of ECCO2R to facilitate ultra-protective ventilation was feasible. A randomized clinical trial is required to assess the overall benefits and harms.



Acute respiratory distress syndrome Mechanical ventilation Extracorporeal carbon dioxide removal Ventilator-induced lung injury 



The trial was made possible thanks to an unrestricted grant from Alung Technologies Inc, Maquet (Getinge Group), and Novalung (Xenios now part of Fresenius Medical). They supported the costs of the data monitoring and site visits, the insurance fees, the supply of the equipment and materials, the shipments and the fees per patient. The grants from the companies amounted to €171,000 and were made available to the European Society of Intensive Care Medicine that supported the costs of the development and running of the eCRF platform, the IT infrastructure, and the administrative costs related to legal matters and contracting (insurance contracts, data use agreements, and hospital contracts).

Members of the Data and Safety Monitoring Board:

Jukka Takala, Chair (University Hospital Bern, Switzerland); Lluis Blanch Torra (Institut Universitari Fundació Parc Taulí-Universitat Autònoma de Barcelona, Spain); Christian Mélot (Erasme University Hospital, Brussel, Belgium)

Investigators of the SUPERNOVA trial:

Belgium: Jacques Creteur, Alexandre Brasseur (Erasme Hospital, Brussel); Daniel de Backer (CHIREC Hospitals, Brussel); Eric Hoste, Filip de Somer, Luc de Crop (Ghent University Hospital); Bernard Lambermont (University Hospital Liège).

Canada: Martin Dres, Orla Smith (St. Michael’s Hospital, Toronto).

France: Nicolas Brechot (Hôpital Pitié-Salpêtrière, Paris); Caroline Fritz, Antoine Kimmoun (Centre Hospitalier Universitaire de Nancy); Nadia Aissaoui, Emmanuel Guerot (Hôpital Européen Georges Pompidou, Paris Hôpital Nord); Laurent Papazian, Jean-Marie Forel (AP-HM Hopital Nord Marseille); Francois Belocncle, Marc Pierrot (Centre Hospitalier Universitaire Angers); Lucie Vettoretti, Hadrien Winiszewski (Centre Hospitalier Universitaire de Besançon); Xavier Repesse, Cyril Charron (Hopital Ambroise Paré, Paris); Didier Dreyfuss, Stephane Gaudry (Hôpital Louis Mourier, Paris).

Germany: Stephan Strassmann, Michaela Merten (Kliniken der Stadt, Köln); Lars Oliver Harmisch (Universitätsmedizin, Göttinge).

Italy: Rosario Urbino, Andrea Costamagna, Chiara Bonetto (Città della Salute e della Scienza di Torino); Davide Eleuteri, Gennaro de Pascale (Università Cattolica-Policlinico Universitario A.Gemelli, Roma); Antonio Braschi, Giorgio Iotti (Fondazione IRCCS Policlinico San Matteo, Pavia); Francesco Pugliese, Guglielmo Tellan, Silvia Corradini (Policlinico Umberto I, Roma); Nicola Bottino, Chiara Abbruzzese (Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milano).

Netherlands: Jozef Kesecioglu, Marc Platenkamp, Diederik van Dijk (University Medical Center, Utrecht).

Spain: Jordi Riera del Brio, Eduard Argudo (Hospital Universitari Vall d’Hebron, Barcelona); Indalecio Moran Chorro, Francisco Parrilla Gomez (Hospital de la Santa Creu i Sant Pau, Barcelona)

The authors wish to thank Luciano Gattinoni, MD. His criticisms and comments on the present study made this work better but most importantly will influence how results of the present study will impact the future scientific development of ECCO2R in ARDS. The authors thank Claudia Filippini Ph.D. for the support in statistical analysis.

European Society of Intensive Care Medicine Trials Group and the “Strategy of Ultra-Protective lung ventilation with Extracorporeal CO2 Removal for New-Onset moderate to seVere ARDS” (SUPERNOVA) investigators:

Ewan C. Goligher3, Daniel Brodie5, Antonio Pesenti6, Richard Beale7, Laurent Brochard3, Jean-Daniel Chiche8, Eddy Fan9, Daniel de Backer10, Guy Francois11, Niall Ferguson9, John Laffey12, Alain Mercat13, Daniel F. Mc Auley14, Thomas Müller15, Michael Quintel16, Jean-Louis Vincent17, Fabio Silvio Taccone17, Harlinde Peperstraete18, Philippe Morimont19, Matthieu Schmidt1, Bruno Levy20, Jean-Luc Diehl21, Christophe Guervilly22, Gilles Capelier23, Antoine Vieillard-Baron24, Jonathan Messika25, Christian Karagiannidis26, Onnen Moerer16, Rosario Urbino2, Massimo Antonelli27, Francesco Mojoli28, Francesco Alessandri29, Giacomo Grasselli6, Dirk Donker30, Ricard Ferrer31, Jordi Mancebo32 Arthur S. Slutsky3

5Division of Pulmonary, Allergy, and Critical Care Medicine, College of Physicians and Surgeons, Columbia University, New York, New York; and New York–Presbyterian Hospital, New York, New York USA; 6Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; 7Guy’s and St. Thomas’ NHS Foundation Trust, London, UK; 8Hôpital Cochin, Université Paris Descartes, France; 9Toronto General Hospital, University of Toronto, Canada; 10Hôpital de Braine l’Alleud-Waterloo, Université Libre de Bruxelles, Belgium; 11European Society of Intensive Care Medicine, Brussels, Belgium; 12Galway University Hospitals and National University of Ireland, Galway, Ireland; 13Centre Hospitalier Universitaire, University of Angers, France; 14Centre for Experimental Medicine, Queen’s University Belfast and Regional Intensive Care Unit, Royal Victoria Hospital, Belfast, UK; 15University Hospital Regensburg, Regensburg, Germany; 16Universitätsmedizin Göttingen, Germany; 17Erasme University Hospital, Université Libre de Bruxelles, Belgium; 18Ghent University Hospital, Belgium; 19University Hospital Liège, Belgium; 20Service de Réanimation Médicale Brabois, CHRU Nancy, Pôle Cardio-Médico-Chirurgical, INSERM U1116, Faculté de Médecine, 54511 Vandoeuvre-les-Nancy, France; Université de Lorraine, Nancy, France; 21Hôpital Européen Georges Pompidou, Paris, France; 22AP-HM, Hôpital Nord, Service de médecine intensive-réanimation, Marseille, France; 23Centre Hospitalier Universitaire de Besançon, France; 24Hôpital Ambroise Paré, Paris, France; 25Hôpital Louis Mourier, Paris, France; 26Kliniken der Stadt Köln and University Witten/Herdecke, Köln, Germany; 27Fondazione Policlinico Universitario A.Gemelli IRCCS, Roma, Italy; 28Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 29Policlinico Umberto I, Roma, Italy; 30University Medical Center, Utrecht University Medical Center, Utrecht, Netherlands; 31Hospital Universitari Vall d’Hebron, Barcelona, Spain; 32Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

Compliance with ethical standards

Conflicts of interest

Dr. Goligher reports receiving personal fees and research support in the form of equipment from Getinge. Dr. Brodie receives research support from ALung Technologies; he was previously on their medical advisory board. He is currently on the medical advisory boards for Baxter and BREETHE. Dr. Ferguson reports receiving personal fees from Getinge, Baxter, and Sedana Medical. Dr. Slutsky reports receiving personal fees from Getinge, Baxter, and Novalung/Xenios.

Ethical approval

The study was approved by institutional review boards at each of the 23 study sites.

Informed consent

Informed consent was obtained from patients or legally authorized surrogates.

Supplementary material

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Supplementary material 1 (DOCX 22 kb)
134_2019_5567_MOESM2_ESM.xlsx (15 kb)
Supplementary material 2 (XLSX 14 kb)
134_2019_5567_MOESM3_ESM.docx (13 kb)
Supplementary material 3 (DOCX 13 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Alain Combes
    • 1
  • Vito Fanelli
    • 2
  • Tai Pham
    • 3
  • V. Marco Ranieri
    • 4
    Email author
  • On behalf of the European Society of Intensive Care Medicine Trials Group and the “Strategy of Ultra-Protective lung ventilation with Extracorporeal CO2 Removal for New-Onset moderate to severe ARDS” (SUPERNOVA) investigators
  1. 1.Institute of Cardio-metabolism and Nutrition, and Service de médecine intensive-réanimation, Institut de Cardiologie, APHP Hôpital Pitié–SalpêtrièreSorbonne Université, INSERM, UMRS_1166-ICANParisFrance
  2. 2.Città della Salute e della Scienza di Torino, Department of Anesthesia and Intensive Care MedicineUniversity of TurinTurinItaly
  3. 3.Keenan Research Center of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Interdepartmental Division of Critical Care MedicineUniversity of TorontoTorontoCanada
  4. 4.Alma Mater Studiorum – Università di Bologna, Dipartimento di Scienze Mediche e Chirurgiche, Anesthesia and Intensive Care MedicinePoliclinico di Sant’OrsolaBolognaItaly

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