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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Janus Christian Jakobsen
  • Theis Lange
  • Helena Levin
  • Jan Bělohlávek
  • Clifton Callaway
  • Alain Cariou
  • Jan Hovdenes
  • Michael Joannidis
  • Per Nordberg
  • Mauro Oddo
  • Paolo Pelosi
  • Hans Kirkegaard
  • Glenn Eastwood
  • Christian Rylander
  • Manoj Saxena
  • Christian Storm
  • Fabio Silvio Taccone
  • Matthew P. Wise
  • Matt P.G. Morgan
  • Paul Young
  • Alistair Nichol
  • Susann Ullén
Organisations
External organisations
  • Copenhagen University Hospital
  • Holbæk Hospital
  • University of Southern Denmark
  • University of Copenhagen
  • General University Hospital in Prague
  • University of Pittsburgh
  • Cochin Hospital
  • Oslo university hospital
  • Medical University of Innsbruck
  • Karolinska Institutet
  • Lausanne University Hospital
  • University of Genoa
  • Ospedale Policlinico San Martino
  • Aarhus University Hospital
  • Austin Hospital
  • Sahlgrenska Academy
  • University of New South Wales
  • Charité - University Medicine Berlin
  • Johns Hopkins University School of Medicine
  • Free University of Brussels (ULB)
  • University Hospital of Wales
  • Medical Research Institute of New Zealand
  • St Vincent's University Hospital
  • Monash University
  • Alfred Hospital
  • Skåne University Hospital
  • Helsingborg Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems
Original languageEnglish
Article number831
JournalTrials
Volume21
Issue number1
Publication statusPublished - 2020 Oct 7
Publication categoryResearch
Peer-reviewedYes