Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest : A statistical analysis plan
(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.
(Less)
- author
- organization
-
- Cardiology
- Brain Injury After Cardiac Arrest (research group)
- Center for cardiac arrest (research group)
- Neurology, Lund
- Anesthesiology and Intensive Care
- Molecular Cardiology (research group)
- SWECRIT (research group)
- Clinical Sciences, Helsingborg
- SEBRA Sepsis and Bacterial Resistance Alliance (research group)
- publishing date
- 2020-10-07
- 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
- 2024-05-15 20:56:51
@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}}, }