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

Y1 - 2020

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 - Journal article

C2 - 33028425

AN - SCOPUS:85092309127

VL - 21

JO - Trials

JF - Trials

SN - 1745-6215

IS - 1

M1 - 831

ER -