A statistical analysis protocol for the time-differentiated target temperature management after out-of-hospital cardiac arrest (TTH48) clinical trial

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DOI

  • Hans Kirkegaard
  • Asger Roer Pedersen
  • Ville Pettilä, Division of Intensive Care, Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Hospital, Helsinki, Finland., inselspital, bern university hospital, university of bern, bern, switzerland
  • ,
  • Jakob Hjort
  • Bodil Steen Rasmussen
  • Inge de Haas, Department of Anaesthesiology and Intensive Care Medicine, Aalborg University Hospital, Aalborg, Denmark.
  • ,
  • Jørgen Feldbæk Nielsen
  • Susanne Ilkjær
  • ,
  • Anne Kaltoft
  • ,
  • Anni Nørgaard Jeppesen
  • Anders Morten Grejs
  • Christophe Henri Valdemar Duez
  • Alf Inge Larsen, Department of Cardiology, Stavanger University Hospital, Stavanger, Norway.
  • ,
  • Valdo Toome, Department of Anaesthesiology, Intensive Care and Emergency Medicine, North Estonia Medical Centre, Tallinn, Estonia.
  • ,
  • Urmet Arus, Department of Intensive Cardiac Care, North Estonia Medical Centre, Tallinn, Estonia.
  • ,
  • Fabio Silvio Taccone, Department of Intensive Care, Erasmus Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.
  • ,
  • Christian Storm, Department of Internal Medicine, Nephrology and Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • ,
  • Timo Laitio, Department of Anaesthesiology and Intensive Care, University of Turku, Turku, Finland., Division of Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland
  • ,
  • Markus B Skrifvars, Division of Intensive Care, Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Hospital, Helsinki, Finland., Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University Melbourne, Monash, Australia
  • ,
  • Eldar Søreide, Department of Anaesthesiology and Intensive Care, Stavanger University Hospital, Stavanger, Norway., Department of Clinical Medicine, University of Bergen

BACKGROUND: The TTH48 trial aims to determine whether prolonged duration (48 hours) of targeted temperature management (TTM) at 33 (±1) °C results in better neurological outcomes compared to standard duration (24 hours) after six months in comatose out-of-hospital cardiac arrest (OHCA) patients.

METHODS: TTH48 is an investigator-initiated, multicentre, assessor-blinded, randomised, controlled superiority trial of 24 and 48 hours of TTM at 33 (±1) ° C performed in 355 comatose OHCA patients aged 18 to 80 years who were admitted to ten intensive care units (ICUs) in six Northern European countries. The primary outcome of the study is the Cerebral Performance Category (CPC) score observed at six months after cardiac arrest. CPC scores of 1 and 2 are defined as good neurological outcomes, and CPC scores of 3, 4 and 5 are defined as poor neurological outcomes. The secondary outcomes are as follows: mortality within six months after cardiac arrest, CPC at hospital discharge, Glasgow Coma Scale (GCS) score on day 4, length of stay in ICU and at hospital and the presence of any adverse events such as cerebral, circulatory, respiratory, gastrointestinal, renal, metabolic measures, infection or bleeding. With the planned sample size, we have 80% power to detect a 15% improvement in good neurological outcomes at a two-sided statistical significance level of 5%.

DISCUSSION: We present a detailed statistical analysis protocol (SAP) that specifies how primary and secondary outcomes should be evaluated. We also predetermine covariates for adjusted analyses and pre-specify sub-groups for sensitivity analyses. This pre-planned SAP will reduce analysis bias and add validity to the findings of this trial on the effect of length of TTM on important clinical outcomes after cardiac arrest.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT01689077 , 17 September 2012.

OriginalsprogEngelsk
TidsskriftScandinavian Journal of Trauma, Resuscitation and Emergency Medicine
Vol/bind24
Nummer1
Sider (fra-til)138
ISSN1757-7241
DOI
StatusUdgivet - 28 nov. 2016

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