BACKGROUND: Basic management for patients who have suffered a cardiac arrest and are admitted to an intensive care unit (ICU) after resuscitation includes setting targets for blood pressure and managing sedation and temperature. However, optimal targets and management are unknown. METHODS: The STEPCARE (Sedation, Temperature and Pressure after Cardiac Arrest and Resuscitation) trial is a multicenter, parallel-group, randomized, factorial, superiority trial in which sedation, temperature, and blood pressure strategies will be studied in three separate comparisons (SED-CARE, TEMP-CARE, and MAP-CARE). The trial population will be adults admitted to intensive care who are comatose after resuscitation from out-of-hospital cardiac arrest. The primary outcome will be all-cause mortality, and the secondary outcomes will be poor functional outcome (modified Rankin Scale 4-6), Health-Related Quality of Life using EQ-VAS, and specific serious adverse events in the intensive care unit predefined for each trial. All outcomes will be assessed at 6 months after randomization. The prognosticators, outcome assessors, statisticians, data managers, steering group, and manuscript writers will be blinded to treatment allocation. This statistical analysis plan includes a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Analyses will be conducted according to the intention-to-treat principle, that is, all randomized participants with available data will be included. The analyses will be performed independently by two statisticians following the present plan. CONCLUSION: This statistical analysis plan describes the statistical analyses for the STEPCARE trial in detail. The aim of this predefined statistical analysis plan is to minimize the risk of analysis bias.

1st Faculty of Medicine Charles University Prague Czech Republic

2nd Department of Internal Medicine Cardiovascular Medicine General University Hospital Prague Czech Republic

Adult Critical Care University Hospital of Wales Cardiff UK

Anaesthesia and Intensive Care Department of Clinical Sciences Lund University Skåne University Hospital Malmö Sweden

Anaesthesia and Intensive Care Pordenone Hospital Azienda Sanitaria Friuli Occidentale Italy

Anesthesia and Intensive Care Department of Clinical Sciences Lund Lund University Sweden

Anesthesiology and Intensive Care Department of Clinical Sciences Helsingborg Hospital Lund Lund University Lund Sweden

Anglia Ruskin School of Medicine and MTRC ARU Essex UK

Australian and New Zealand Intensive Care Research Centre Monash University Melbourne Victoria Australia

Centre for Healthcare Evaluation Device Assessment and Research Cardiff and Vale University Health Board Cardiff UK

Charité Universitätsmedizin Berlin Corporate Member of Freie Universität and Humboldt Universität zu Berlin Department of Neurology Berlin Germany

Copenhagen Trial Unit Centre for Clinical Intervention Research The Capital Region Copenhagen University Hospital Rigshospitalet Copenhagen Ø Denmark

Critical Care Division and Department of Intensive Care Medicine The George Institute for Global Health Sydney NSW Australia

Critical Care Program The George Institute for Global Health UNSW Sydney Australia

Critical Care University Hospital of Wales Cardiff UK

Department of Anaesthesia and Intensive Care Helsinki University Hospital and University of Helsinki Helsinki Finland

Department of Anaesthesia and Intensive Care Medicine Centre Hospitalier de Luxembourg Luxembourg Luxembourg

Department of Anaesthesia and Intensive Care Medicine Division of Emergencies and Critical Care Oslo University Hospital Oslo Norway

Department of Anaesthesia and Intensive Care Skaraborgs Sjukhus Skövde Sweden

Department of Anaesthesia Critical Care and Pain Medicine Jaber Alahmad Alsabah Hospital Kuwait

Department of Anaesthesiology and Intensive Care Helsingborg Hospital Helsingborg Sweden

Department of Anaesthesiology and Intensive Care Kuopio University Hospital Finland

Department of Anaesthesiology and Intensive Care Medicine Institute of Clinical Sciences Sahlgrenska Academy University of Gothenburg Gothenburg Sweden

Department of Cardiology King's College Hospital NHS Foundation Trust London UK

Department of Cardiology Ziekenhuis Oost Limburg Genk Belgium

Department of Clinical Science Intervention and Technology Karolinska Institute Stockholm Sweden

Department of Clinical Sciences Lund Lund University Lund Sweden

Department of Clinical Sciences Lund Section of Cardiology Skåne University Hospital Scania Sweden

Department of Critical Care Guy's and St Thomas NHS Foundation Trust London UK

Department of Critical Care Portsmouth University Hospitals Trust Portsmouth UK

Department of Critical Care University of Melbourne Melbourne Victoria Australia

Department of Intensive and Perioperative Care Skåne University Hospital Lund University Lund Sweden

Department of Intensive Care Christchurch Hospital New Zealand

Department of Intensive Care Medicine Ghent University Hospital Ghent Belgium

Department of Intensive Care Medicine Inselspital University Hospital Bern Bern Switzerland

Department of Intensive Care Medicine Stavanger University Hospital Stavanger Norway

Department of Nephrology and Medical Intensive Care Charité Universitaetsmedizin Berlin Berlin Germany

Department of Neuroanaesthesiology The Neuroscience Centre Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Neurology and Rehabilitation Skåne University Hospital Lund Sweden

Department of Neurology and Stroke University Hospital Tuebingen Germany

Department of Neurology Helsinki University Hospital and University of Helsinki Helsinki Finland

Department of Operation and Intensive Care Hallands Hospital Halmstad Sweden

Department of Perioperative Medicine Barts Heart Centre St Bartholomew's Hospital London UK

Department of Physiology and Pharmacology Karolinska Institute Stockholm Sweden

Department of Regional Health Research The Faculty of Health Sciences University of Southern Denmark Odense Denmark

Department of Research Development Education and Innovation Skåne University Hospital Lund Sweden

Dipartimento di Scienze Chirurgiche Diagnostiche Integrate University of Genova Italy

Division of Intensive Care and Emergency Medicine Department of Internal Medicine Medical University Insbruck Innsbruck Austria

Essex Cardiothoracic Centre MSE NHSFT Essex UK

German Center for Cardiovascular Research Partner Site Hamburg Lübeck Kiel Germany

Hertie Institute of Clinical Brain Research Germany

Institute for Heart Diseases Wroclaw Medical University Wrocław Poland

Institute of Intensive Care Medicine University Hospital Zurich Zurich Switzerland

Intensive and Perioperative Care Skåne University Hospital Malmö Sweden

Intensive Care Unit Liverpool Hospital South Western Sydney Local Health District Sydney New South Wales Australia

Intensive Care Unit Tampere University Hospital Finland

Intensive Care Unit Wellington Hospital Wellington New Zealand

IRCCS Policlinico San Martino Genova Italy

Istituto Cardiocentro Ticino Lugano Switzerland

King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center Riyadh Saudi Arabia

Klinik für Intensivmedizin Kantonsspital St Gallen St Gallen Switzerland

Lee Kong Chian School of Medicine Nanyang Technological University Singapore Singapore

Leeds General Infirmary The Leeds Teaching Hospitals NHS Trust Leeds UK

Liverpool Hospital South Western Sydney Local Health District Liverpool New South Wales Australia

Lovisenberg Diaconal University College Oslo Norway

Malcolm Fisher Department of Intensive Care Medicine Royal North Shore Hospital St Leonards Australia

Medical Research Institute of New Zealand Wellington New Zealand

Medical School University of Queensland Brisbane Australia

Middlemore Hospital Auckland New Zealand

Neurology Department of Clinical Sciences Lund Lund University Lund Sweden

North Estonia Medical Centre Estonia

Northern Clinical School Sydney Medical School University of Sydney Camperdown New South Wales Australia

OYS Heart Oulu University Hospital MRC Oulu and University of Oulu Oulu Finland

Perioperative Medicine and Intensive Care Karolinska University Hospital Stockholm Sweden

Regional Intensive Care Unit Royal Victoria Hospital Belfast UK

Research Unit of Translational Medicine Research Group of Anaesthesiology Medical Research Center Oulu Oulu University Hospital and University of Oulu Oulu Finland

Royal North Shore Hospital Sydney Australia

School of Cardiovascular and Metabolic Medicine and Sciences BHF Centre of Excellence King's College London UK

South Western Clinical School University of New South Wales Sydney New South Wales Australia

St George Hospital Clinical School University of New South Wales Sydney Australia

St George's University Hospital NHS Foundation Trust London UK

Tampere University Hospital Wellbeing Services County of Pirkanmaa and Tampere University Faculty of Medicine and Health Technology Tampere Finland

Tan Tock Seng Hospital Singapore Singapore

The Alfred Hospital Melbourne Australia

The Australian and New Zealand Intensive Care Research Centre Monash University Melbourne Australia

The George Institute for Global Health Sydney New South Wales Australia

The George Institute for Global Health University of New South Wales Sydney Australia

The Ingham Institute for Applied Medical Research Sydney New South Wales Australia

University College Dublin Clinical Research Centre at St Vincent's University Hospital University College Dublin Dublin Ireland

University Heart Center Lübeck University Hospital Schleswig Holstein Germany

University Hospitals Bristol and Weston UK

University of Eastern Finland Institute of Clinical Medicine Finland

Wellcome Wolfson Institute for Experimental Medicine Queen's University Belfast UK

Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore

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