Detailed statistical analysis plan for the target temperature management after out-of-hospital cardiac arrest trial
1 Department of Anesthesia and Intensive Care, Helsingborg Hospital, Södra Vallgatan 5, Helsingborg, 253 87, Sweden
2 Department of Clinical Sciences, Lund University, Getingevägen 5, Lund, Sweden Lund, 221 85, Sweden
3 Copenhagen Trial Unit, Centre of Clinical Intervention Research, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark
4 Department of Neurology, Skåne University Hospital, Getingevägen 5, Lund, 221 85, Sweden
5 Department of Cardiology, Skåne University Hospital, Getingevägen 5, Lund, 221 85, Sweden
6 Department of Anesthesia and Intensive Care, Skåne University Hospital, Getingevägen 5, Lund, 221 85, Sweden
7 Department of Intensive Care, Geneva University Hospital, 4 Rue Gabrielle-Perret-Gentil, Geneva, 1211, Switzerland
8 The Heart Centre, Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark
9 Department of Intensive Care, Academic Medical Center, Postbus 22700, Amsterdam, NL-1100 DE, Netherlands
10 Department of Anaesthesia, Oslo University Hospital, Rikshospitalet, Songsvannsvejen 20, Oslo, 27, Norway
11 Intensive Care Unit, Leeuwarden Medical Centrum, Borniastraat 38, Leeuwarden, NL8934 AD, Netherlands
12 Intensive Care Unit, Santa Maria degli Angeli, Via Montereale 24, Pordenone, 33170, Italy
13 Department of Anesthesia and Intensive Care, Centre Hospitalier, de Luxembourg, 4 rue Nicolas Ernest Barblé, Luxembourg, L 1210, Luxembourg
14 Adult Critical Care, University Hospital of Wales, Heath Park, Cardiff, CF144XW, UK
15 Department of Intensive Care, Liverpool Hospital, Sydney, Locked Bag 7103, Liverpool BC, NSW, 1871, Australia
Trials 2013, 14:300 doi:10.1186/1745-6215-14-300Published: 17 September 2013
Animal experimental studies and previous randomized trials suggest an improvement in mortality and neurological function with temperature regulation to hypothermia after cardiac arrest. According to a systematic review, previous trials were small, had a risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management (TTM) strategy is not known. To prevent outcome reporting bias, selective reporting and data-driven results, we present the a priori defined detailed statistical analysis plan as an update to the previously published outline of the design and rationale for the TTM trial.
The TTM trial is an investigator-initiated, multicenter, international, randomized, parallel-group, and assessor-blinded clinical trial of temperature management in 950 adult unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients are randomized to a TTM of either 33°C or 36°C after return of spontaneous circulation. The primary outcome is all-cause mortality at maximal follow-up (until end of the trial and a minimum of 180 days). The main secondary outcomes are the composite outcome of all-cause mortality and poor neurological function (Cerebral Performance Category (CPC) 3 and 4, and modified Rankin Scale (mRS) 4 and 5) at hospital discharge and at 180 days; and assessment of safety and harm: bleeding, infections, electrolyte and metabolic disorders, seizures, cardiac arrhythmia, and renal replacement therapy.
The TTM trial investigates potential benefit and harm of two target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.
ClinicalTrials.gov identifier: NCT01020916