TY - JOUR
T1 - Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest
T2 - a statistical analysis plan
AU - Jakobsen, Janus Christian
AU - Dankiewicz, Josef
AU - Lange, Theis
AU - Cronberg, Tobias
AU - Lilja, Gisela
AU - Levin, Helena
AU - Bělohlávek, Jan
AU - Callaway, Clifton
AU - Cariou, Alain
AU - Erlinge, David
AU - Hovdenes, Jan
AU - Joannidis, Michael
AU - Nordberg, Per
AU - Oddo, Mauro
AU - Pelosi, Paolo
AU - Kirkegaard, Hans
AU - Eastwood, Glenn
AU - Rylander, Christian
AU - Saxena, Manoj
AU - Storm, Christian
AU - Taccone, Fabio Silvio
AU - Wise, Matthew P
AU - Morgan, Matt P G
AU - Young, Paul
AU - Nichol, Alistair
AU - Friberg, Hans
AU - Ullén, Susann
AU - Nielsen, Niklas
PY - 2020/10/7
Y1 - 2020/10/7
N2 - 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.
AB - 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.
U2 - 10.1186/s13063-020-04654-y
DO - 10.1186/s13063-020-04654-y
M3 - Article
C2 - 33028425
SN - 1745-6215
VL - 21
SP - 831
JO - Trials
JF - Trials
IS - 1
ER -