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Detailed statistical analysis plan for the target temperature management after out-of-hospital cardiac arrest trial

Nielsen, Niklas LU ; Winkel, Per ; Cronberg, Tobias LU ; Erlinge, David LU ; Friberg, Hans LU ; Gasche, Yvan ; Hassager, Christian ; Horn, Janneke ; Hovdenes, Jan and Kjaergaard, Jesper , et al. (2013) In Trials 14.
Abstract
Background: Animal experimental studies and previous randomized trials suggest an improvement in mortality and neurological function with temperature regulation to hypothermia after cardiac arrest. According to a systematic review, previous trials were small, had a risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management (TTM) strategy is not known. To prevent outcome reporting bias, selective reporting and data-driven results, we present the a priori defined detailed statistical analysis plan as an update to the previously published outline of the design and rationale for the TTM trial. Methods: The TTM trial is an investigator-initiated, multicenter,... (More)
Background: Animal experimental studies and previous randomized trials suggest an improvement in mortality and neurological function with temperature regulation to hypothermia after cardiac arrest. According to a systematic review, previous trials were small, had a risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management (TTM) strategy is not known. To prevent outcome reporting bias, selective reporting and data-driven results, we present the a priori defined detailed statistical analysis plan as an update to the previously published outline of the design and rationale for the TTM trial. Methods: The TTM trial is an investigator-initiated, multicenter, international, randomized, parallel-group, and assessor-blinded clinical trial of temperature management in 950 adult unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients are randomized to a TTM of either 33 degrees C or 36 degrees C after return of spontaneous circulation. The primary outcome is all-cause mortality at maximal follow-up (until end of the trial and a minimum of 180 days). The main secondary outcomes are the composite outcome of all-cause mortality and poor neurological function (Cerebral Performance Category (CPC) 3 and 4, and modified Rankin Scale (mRS) 4 and 5) at hospital discharge and at 180 days; and assessment of safety and harm: bleeding, infections, electrolyte and metabolic disorders, seizures, cardiac arrhythmia, and renal replacement therapy. Conclusion: The TTM trial investigates potential benefit and harm of two target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cardiac arrest, Induced hypothermia, Mortality, Neurological function, Targeted temperature management, Randomized clinical trial, Statistical, analysis plan
in
Trials
volume
14
article number
300
publisher
BioMed Central (BMC)
external identifiers
  • wos:000324857100001
  • scopus:84883892607
  • pmid:24044764
ISSN
1745-6215
DOI
10.1186/1745-6215-14-300
language
English
LU publication?
yes
id
fde4b219-0cd2-47f7-bb22-e1969a7fa0e5 (old id 4098926)
date added to LUP
2016-04-01 14:50:59
date last changed
2020-07-01 03:02:34
@article{fde4b219-0cd2-47f7-bb22-e1969a7fa0e5,
  abstract     = {Background: Animal experimental studies and previous randomized trials suggest an improvement in mortality and neurological function with temperature regulation to hypothermia after cardiac arrest. According to a systematic review, previous trials were small, had a risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management (TTM) strategy is not known. To prevent outcome reporting bias, selective reporting and data-driven results, we present the a priori defined detailed statistical analysis plan as an update to the previously published outline of the design and rationale for the TTM trial. Methods: The TTM trial is an investigator-initiated, multicenter, international, randomized, parallel-group, and assessor-blinded clinical trial of temperature management in 950 adult unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients are randomized to a TTM of either 33 degrees C or 36 degrees C after return of spontaneous circulation. The primary outcome is all-cause mortality at maximal follow-up (until end of the trial and a minimum of 180 days). The main secondary outcomes are the composite outcome of all-cause mortality and poor neurological function (Cerebral Performance Category (CPC) 3 and 4, and modified Rankin Scale (mRS) 4 and 5) at hospital discharge and at 180 days; and assessment of safety and harm: bleeding, infections, electrolyte and metabolic disorders, seizures, cardiac arrhythmia, and renal replacement therapy. Conclusion: The TTM trial investigates potential benefit and harm of two target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.},
  author       = {Nielsen, Niklas and Winkel, Per and Cronberg, Tobias and Erlinge, David and Friberg, Hans and Gasche, Yvan and Hassager, Christian and Horn, Janneke and Hovdenes, Jan and Kjaergaard, Jesper and Kuiper, Michael and Pellis, Tommaso and Stammet, Pascal and Wanscher, Michael and Wise, Matt P. and Aneman, Anders and Wetterslev, Jorn},
  issn         = {1745-6215},
  language     = {eng},
  publisher    = {BioMed Central (BMC)},
  series       = {Trials},
  title        = {Detailed statistical analysis plan for the target temperature management after out-of-hospital cardiac arrest trial},
  url          = {https://lup.lub.lu.se/search/ws/files/4198330/4254926},
  doi          = {10.1186/1745-6215-14-300},
  volume       = {14},
  year         = {2013},
}