Gisela Lilja1, Niklas Nielsen2, Susann Ullén3, Erik Blennow Nordstrom4, Josef Dankiewicz5, Hans Friberg6, Katarina Heimburg4, Janus Christian Jakobsen7, Helena Levin8, Clifton Callaway9, Alain Cariou10, Glenn M Eastwood11, Raimund Helbok12, Jan Hovdenes13, Hans Kirkegaard14, Christoph Leithner15, Matt P G Morgan16, Per Nordberg17, Mauro Oddo18, Paolo Pelosi19, Christian Rylander20, Manoj Saxena21, Fabio Silvio Taccone22, Michal Siranec23, Matthew P Wise16, Paul J Young24, Tobias Cronberg4. 1. Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Neurology, Lund, Sweden. Electronic address: gisela.lilja@med.lu.se. 2. Lund University, Helsingborg Hospital, Department of Clinical Sciences Lund, Anesthesiology and Intensive Care, Helsingborg, Sweden. 3. Clinical Studies Sweden - Forum South, Skane University Hospital, Lund, Sweden. 4. Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Neurology, Lund, Sweden. 5. Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Cardiology, Lund, Sweden. 6. Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Anesthesiology and Intensive Care, Malmö, Sweden. 7. Copenhagen Trial Unit, Copenhagen, Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Department of Cardiology, Holbæk Hospital, Copenhagen, Denmark. 8. Lund University, Skane University Hospital, Department of Clinical Sciences, Research and Education, Lund, Sweden. 9. Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, PA, USA. 10. Cochin University Hospital (APHP) and Paris Descartes University, Paris, France. 11. Australian and New Zealand Intensive Care Research Centre, School of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. 12. Department of Neurology, Neurological Intensive Care Unit, Medical University Innsbruck, Innsbruck, Austria. 13. Department of Anesthesiology, Rikshospitalet, Oslo University Hospital, Oslo, Norway. 14. Research Center for Emergency Medicine, Aarhus University Hospital and Aarhus University, Aarhus, Denmark. 15. Department of Neurology, Charité University Medicine, Berlin, Germany. 16. Adult Critical Care, University Hospital of Wales, Cardiff, United Kingdom. 17. Department of Medicine, Center for Resuscitation Science, Karolinska Institute, Solna, Sweden. 18. Department of Intensive Care Medicine, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 19. Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy; San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy. 20. Department of Anaesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden. 21. Bankstown Hospital, South Western Sydney Local Health District, Sydney, Australia; Critical Care Division, The George Institute for Global Health, University of New South Wales, Sydney, Australia. 22. Erasme Hospital, Université Libre de Bruxelles, Department of Intensive Care, Brussels, Belgium. 23. Department of Medicine - Department of Cardiovascular Medicine, Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. 24. Medical Research Institute of New Zealand, Wellington, New Zealand.
Abstract
AIMS: The TTM2-trial is a multi-centre randomised clinical trial where targeted temperature management (TTM) at 33 °C will be compared with normothermia and early treatment of fever (≥37.8 °C) after Out-of-Hospital Cardiac Arrest (OHCA). This paper presents the design and rationale of the TTM2-trial follow-up, where information on secondary and exploratory outcomes will be collected. We also present the explorative outcome analyses which will focus on neurocognitive function and societal participation in OHCA-survivors. METHODS: Blinded outcome-assessors will perform follow-up at 30-days after the OHCA with a telephone interview, including the modified Rankin Scale (mRS) and the Glasgow Outcome Scale Extended (GOSE). Face-to-face meetings will be performed at 6 and 24-months, and include reports on outcome from several sources of information: clinician-reported: mRS, GOSE; patient-reported: EuroQol-5 Dimensions-5 Level responses version (EQ-5D-5L), Life satisfaction, Two Simple Questions; observer-reported: Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest version (IQCODE-CA) and neurocognitive performance measures: Montreal Cognitive Assessment, (MoCA), Symbol Digit Modalities Test (SDMT). Exploratory analyses will be performed with an emphasis on brain injury in the survivors, where the two intervention groups will be compared for potential differences in neuro-cognitive function (MoCA, SDMT) and societal participation (GOSE). Strategies to increase inter-rater reliability and decrease missing data are described. DISCUSSION: The TTM2-trial follow-up is a pragmatic yet detailed pre-planned and standardised assessment of patient's outcome designed to ensure data-quality, decrease missing data and provide optimal conditions to investigate clinically relevant effects of TTM, including OHCA-survivors' neurocognitive function and societal participation.
RCT Entities:
AIMS: The TTM2-trial is a multi-centre randomised clinical trial where targeted temperature management (TTM) at 33 °C will be compared with normothermia and early treatment of fever (≥37.8 °C) after Out-of-Hospital Cardiac Arrest (OHCA). This paper presents the design and rationale of the TTM2-trial follow-up, where information on secondary and exploratory outcomes will be collected. We also present the explorative outcome analyses which will focus on neurocognitive function and societal participation in OHCA-survivors. METHODS: Blinded outcome-assessors will perform follow-up at 30-days after the OHCA with a telephone interview, including the modified Rankin Scale (mRS) and the Glasgow Outcome Scale Extended (GOSE). Face-to-face meetings will be performed at 6 and 24-months, and include reports on outcome from several sources of information: clinician-reported: mRS, GOSE; patient-reported: EuroQol-5 Dimensions-5 Level responses version (EQ-5D-5L), Life satisfaction, Two Simple Questions; observer-reported: Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest version (IQCODE-CA) and neurocognitive performance measures: Montreal Cognitive Assessment, (MoCA), Symbol Digit Modalities Test (SDMT). Exploratory analyses will be performed with an emphasis on brain injury in the survivors, where the two intervention groups will be compared for potential differences in neuro-cognitive function (MoCA, SDMT) and societal participation (GOSE). Strategies to increase inter-rater reliability and decrease missing data are described. DISCUSSION: The TTM2-trial follow-up is a pragmatic yet detailed pre-planned and standardised assessment of patient's outcome designed to ensure data-quality, decrease missing data and provide optimal conditions to investigate clinically relevant effects of TTM, including OHCA-survivors' neurocognitive function and societal participation.
Authors: Marion Moseby-Knappe; Helena Levin; Kaj Blennow; Susann Ullén; Henrik Zetterberg; Gisela Lilja; Josef Dankiewicz; Janus Christian Jakobsen; Alice Lagebrant; Hans Friberg; Alistair Nichol; Kate Ainschough; Glenn M Eastwood; Matt P Wise; Matthew Thomas; Thomas Keeble; Alain Cariou; Christoph Leithner; Christian Rylander; Joachim Düring; Jan Bělohlávek; Anders Grejs; Ola Borgquist; Johan Undén; Maryline Simon; Vinzent Rolny; Alex Piehler; Tobias Cronberg; Niklas Nielsen Journal: Resusc Plus Date: 2022-06-02
Authors: Chiara Robba; Niklas Nielsen; Josef Dankiewicz; Rafael Badenes; Denise Battaglini; Lorenzo Ball; Iole Brunetti; Wendel-Garcia Pedro David; Paul Young; Glenn Eastwood; Michelle S Chew; Janus Jakobsen; Johan Unden; Matthew Thomas; Michael Joannidis; Alistair Nichol; Andreas Lundin; Jacob Hollenberg; Gisela Lilja; Naomi E Hammond; Manoj Saxena; Annborn Martin; Miroslav Solar; Fabio Silvio Taccone; Hans A Friberg; Paolo Pelosi Journal: BMJ Open Date: 2022-03-03 Impact factor: 2.692
Authors: Margareta Lang; Christoph Leithner; Michael Scheel; Martin Kenda; Tobias Cronberg; Joachim During; Christian Rylander; Martin Annborn; Josef Dankiewicz; Nicolas Deye; Thomas Halliday; Jean-Baptiste Lascarrou; Thomas Matthew; Peter McGuigan; Matt Morgan; Matthew Thomas; Susann Ullén; Johan Undén; Niklas Nielsen; Marion Moseby-Knappe Journal: Resusc Plus Date: 2022-10-12
Authors: Katarina Heimburg; Gisela Lilja; Åsa B Tornberg; Susann Ullén; Erik Blennow Nordström; Hans Friberg; Niklas Nielsen; Lisa Gregersen Østergaard; Anders M Grejs; Helen Hill; Thomas R Keeble; Hans Kirkegaard; Marco Mion; Christian Rylander; Magnus Segerström; Johan Undén; Matthew P Wise; Tobias Cronberg Journal: Resusc Plus Date: 2021-01-29
Authors: Erik Blennow Nordström; Gisela Lilja; Susanna Vestberg; Susann Ullén; Hans Friberg; Niklas Nielsen; Katarina Heimburg; Lars Evald; Marco Mion; Magnus Segerström; Anders M Grejs; Thomas Keeble; Hans Kirkegaard; Hanna Ljung; Sofia Rose; Matthew P Wise; Christian Rylander; Johan Undén; Tobias Cronberg Journal: BMC Cardiovasc Disord Date: 2020-10-07 Impact factor: 2.298
Authors: Janus Christian Jakobsen; Josef Dankiewicz; Theis Lange; Tobias Cronberg; Gisela Lilja; Helena Levin; Jan Bělohlávek; Clifton Callaway; Alain Cariou; David Erlinge; Jan Hovdenes; Michael Joannidis; Per Nordberg; Mauro Oddo; Paolo Pelosi; Hans Kirkegaard; Glenn Eastwood; Christian Rylander; Manoj Saxena; Christian Storm; Fabio Silvio Taccone; Matthew P Wise; Matt P G Morgan; Paul Young; Alistair Nichol; Hans Friberg; Susann Ullén; Niklas Nielsen Journal: Trials Date: 2020-10-07 Impact factor: 2.279