TY - JOUR
T1 - A statistical analysis protocol for the time-differentiated target temperature management after out-of-hospital cardiac arrest (TTH48) clinical trial
AU - Kirkegaard, Hans
AU - Pedersen, Asger Roer
AU - Pettilä, Ville
AU - Hjort, Jakob
AU - Rasmussen, Bodil Steen
AU - de Haas, Inge
AU - Nielsen, Jørgen Feldbæk
AU - Ilkjær, Susanne
AU - Kaltoft, Anne
AU - Jeppesen, Anni Nørgaard
AU - Grejs, Anders Morten
AU - Duez, Christophe Henri Valdemar
AU - Larsen, Alf Inge
AU - Toome, Valdo
AU - Arus, Urmet
AU - Taccone, Fabio Silvio
AU - Storm, Christian
AU - Laitio, Timo
AU - Skrifvars, Markus B
AU - Søreide, Eldar
PY - 2016/11/28
Y1 - 2016/11/28
N2 - 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:
AB - 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:
KW - Cardiac arrest
KW - Cerebral performance category
KW - Critical care
KW - Heart arrest
KW - Intensive care
KW - Mortality
KW - Out-of-hospital
KW - Randomised controlled trial
KW - Targeted temperature management
UR - http://www.scopus.com/inward/record.url?scp=84999116029&partnerID=8YFLogxK
U2 - 10.1186/s13049-016-0334-0
DO - 10.1186/s13049-016-0334-0
M3 - Journal article
C2 - 27894327
SN - 1757-7241
VL - 24
SP - 138
JO - Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
JF - Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
IS - 1
M1 - 138
ER -