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

Jakobsen, Janus Christian ; Dankiewicz, Josef LU orcid ; Lange, Theis ; Cronberg, Tobias LU ; Lilja, Gisela LU ; Levin, Helena LU ; Bělohlávek, Jan ; Callaway, Clifton ; Cariou, Alain and Erlinge, David LU orcid , et al. (2020) In Trials 21(1).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Trials
volume
21
issue
1
article number
831
publisher
BioMed Central (BMC)
external identifiers
  • pmid:33028425
  • scopus:85092309127
ISSN
1745-6215
DOI
10.1186/s13063-020-04654-y
language
English
LU publication?
yes
id
5d866364-5630-49fb-a929-65a80ca7cb69
date added to LUP
2020-11-09 08:52:40
date last changed
2024-01-17 14:35:15
@article{5d866364-5630-49fb-a929-65a80ca7cb69,
  abstract     = {{<p>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. </p>}},
  author       = {{Jakobsen, Janus Christian and Dankiewicz, Josef and Lange, Theis and Cronberg, Tobias and Lilja, Gisela and Levin, Helena and Bělohlávek, Jan and Callaway, Clifton and Cariou, Alain and Erlinge, David and Hovdenes, Jan and Joannidis, Michael and Nordberg, Per and Oddo, Mauro and Pelosi, Paolo and Kirkegaard, Hans and Eastwood, Glenn and Rylander, Christian and Saxena, Manoj and Storm, Christian and Taccone, Fabio Silvio and Wise, Matthew P. and Morgan, Matt P.G. and Young, Paul and Nichol, Alistair and Friberg, Hans and Ullén, Susann and Nielsen, Niklas}},
  issn         = {{1745-6215}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Trials}},
  title        = {{Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest : A statistical analysis plan}},
  url          = {{http://dx.doi.org/10.1186/s13063-020-04654-y}},
  doi          = {{10.1186/s13063-020-04654-y}},
  volume       = {{21}},
  year         = {{2020}},
}