Journal article
Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: a statistical analysis plan.
- Jakobsen JC Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Tagensvej 22, Copenhagen, Denmark. jcj@ctu.dk.
- Dankiewicz J Department of Clinical Sciences, Cardiology, Lund University, Skåne University Hospital, Lund, Sweden.
- Lange T Section of Biostatistics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Cronberg T Department of Clinical Sciences, Neurology, Lund University, Skåne University Hospital, Lund, Sweden.
- Lilja G Department of Clinical Sciences, Neurology, Lund University, Skåne University Hospital, Lund, Sweden.
- Levin H Department of Clinical Sciences, Research and Education, Lund University, Skåne University Hospital, Lund, Sweden.
- Bělohlávek J 2nd Department of Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
- Callaway C Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
- Cariou A Medical Intensive Care Unit, Cochin University Hospital (APHP) and Paris Descartes University, Paris, France.
- Erlinge D Department of Clinical Sciences, Cardiology, Lund University, Skåne University Hospital, Lund, Sweden.
- Hovdenes J Department of Anesthesia and Intensive Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
- Joannidis M Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria.
- Nordberg P Department of Medicine, Center for Resuscitation Science, Karolinska Institute, Solna, Sweden.
- Oddo M Department of Intensive Care Medicine, Faculty of Biology and Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) - University Hospital, University of Lausanne, Lausanne, Switzerland.
- Pelosi P Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.
- Kirkegaard H Research Center for Emergency Medicine, Department of Clinical Medicine, Aarhus University Hospital and Aarhus University, Aarhus N, Denmark.
- Eastwood G Department of Intensive Care, Austin Hospital, Heidelberg, Australia.
- Rylander C Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Saxena M Bankstown Hospital Clinical School and The George Institute for Global Health, University of New South Wales, Kensington, Australia.
- Storm C Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany.
- Taccone FS Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.
- Wise MP Adult Critical Care, University Hospital of Wales, Cardiff, UK.
- Morgan MPG Adult Critical Care, University Hospital of Wales, Cardiff, UK.
- Young P Medical Research Institute of New Zealand, Wellington, New Zealand.
- Nichol A University Collage Dublin-Clinical Research Centre, St Vincent's University Hospital, Dublin, Ireland.
- Friberg H Department of Clinical Sciences, Anesthesia & Intensive Care, Lund University, Skåne University Hospital, Lund, Sweden.
- Ullén S Clinical Studies Sweden, Skåne University Hospital, Lund, Sweden.
- Nielsen N Department of Clinical Sciences Lund, Anesthesia & Intensive Care, Lund University, Helsingborg Hospital, Lund, Sweden.
- 2020-10-08
Published in:
- Trials. - 2020
English
BACKGROUND
To date, targeted temperature management (TTM) is the only neuroprotective intervention after resuscitation from cardiac arrest that is recommended by guidelines. The evidence on the effects of TTM is unclear.
METHODS/DESIGN
The Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) trial is an international, multicentre, parallel group, investigator-initiated, randomised, superiority trial in which TTM with a target temperature of 33 °C after cardiac arrest will be compared with a strategy to maintain normothermia and active treatment of fever (≥ 37.8 °C). Prognosticators, outcome assessors, the steering group, the trial coordinating team, and trial statisticians will be blinded to treatment allocation. The primary outcome will be all-cause mortality at 180 days after randomisation. We estimate a 55% mortality in the targeted normothermia group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The secondary neurological outcome will be poor functional outcome (modified Rankin scale 4-6) at 180 days after cardiac arrest. In this paper, a detailed statistical analysis plan is presented, including a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Final analyses will be conducted independently by two qualified statisticians following the present plan.
DISCUSSION
This SAP, which was prepared before completion of enrolment, should increase the validity of the TTM trial by mitigation of analysis-bias.
To date, targeted temperature management (TTM) is the only neuroprotective intervention after resuscitation from cardiac arrest that is recommended by guidelines. The evidence on the effects of TTM is unclear.
METHODS/DESIGN
The Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) trial is an international, multicentre, parallel group, investigator-initiated, randomised, superiority trial in which TTM with a target temperature of 33 °C after cardiac arrest will be compared with a strategy to maintain normothermia and active treatment of fever (≥ 37.8 °C). Prognosticators, outcome assessors, the steering group, the trial coordinating team, and trial statisticians will be blinded to treatment allocation. The primary outcome will be all-cause mortality at 180 days after randomisation. We estimate a 55% mortality in the targeted normothermia group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The secondary neurological outcome will be poor functional outcome (modified Rankin scale 4-6) at 180 days after cardiac arrest. In this paper, a detailed statistical analysis plan is presented, including a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Final analyses will be conducted independently by two qualified statisticians following the present plan.
DISCUSSION
This SAP, which was prepared before completion of enrolment, should increase the validity of the TTM trial by mitigation of analysis-bias.
- Language
-
- English
- Open access status
- gold
- Identifiers
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- DOI 10.1186/s13063-020-04654-y
- PMID 33028425
- Persistent URL
- https://sonar.ch/global/documents/239279
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