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

Janus Christian Jakobsen, Josef Dankiewicz, Theis Lange, Tobias Cronberg, Gisela Lilja, Helena Levin, Jan Bělohlávek, Clifton Callaway, Alain Cariou, David Erlinge, Jan Hovdenes, Michael Joannidis, Per Nordberg, Mauro Oddo, Paolo Pelosi, Hans Kirkegaard, Glenn Eastwood, Christian Rylander, Manoj Saxena, Christian StormFabio Silvio Taccone, Matthew P. Wise, Matt P.G. Morgan, Paul Young, Alistair Nichol, Hans Friberg, Susann Ullén, Niklas Nielsen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number831
JournalTrials
Volume21
Issue number1
DOIs
Publication statusPublished - Oct 7 2020

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology (medical)

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