Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: A statistical analysis plan

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title = "Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: A statistical analysis plan",
abstract = "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. ",
author = "Jakobsen, {Janus Christian} and Josef Dankiewicz and Theis Lange and Tobias Cronberg and Gisela Lilja and Helena Levin and Jan B{\v e}lohl{\'a}vek and Clifton Callaway and Alain Cariou and David Erlinge and Jan Hovdenes and Michael Joannidis and Per Nordberg and Mauro Oddo and Paolo Pelosi and Hans Kirkegaard and Glenn Eastwood and Christian Rylander and Manoj Saxena and Christian Storm and Taccone, {Fabio Silvio} and Wise, {Matthew P.} and Morgan, {Matt P.G.} and Paul Young and Alistair Nichol and Hans Friberg and Susann Ull{\'e}n and Niklas Nielsen",
year = "2020",
month = oct,
day = "7",
doi = "10.1186/s13063-020-04654-y",
language = "English",
volume = "21",
journal = "Trials",
issn = "1745-6215",
publisher = "BioMed Central (BMC)",
number = "1",