title: Protocol and statistical analysis plan for the Randomised Evaluation of Active Control of Temperature versus Ordinary Temperature Management (REACTOR) trial.
abstract: BACKGROUND
  Body temperature can be reduced in febrile patients in the intensive care unit using medicines and physical cooling devices, but it is not known whether systematically preventing and treating fever reduces body temperature compared with standard care.
  
  
  OBJECTIVE
  To describe the study protocol and statistical analysis plan for the Randomised Evaluation of Active Control of Temperature versus Ordinary Temperature Management (REACTOR) trial.
  
  
  METHODS
  Protocol for a phase II, multicentre trial to be conducted in Australian and New Zealand ICUs admitting adult patients. We will recruit 184 adults without acute brain injury who are expected to be ventilated in the ICU beyond the day after randomisation. We will use open, random, parallel assignment to systematic prevention and treatment of fever, or to standard temperature management.
  
  
  METHODS
  The primary end point will be mean body temperature, calculated from body temperatures measured 6-hourly for 7 days (168 hours) or until ICU discharge, whichever is sooner. Secondary end points are ICU-free days, in-hospital and cause-specific mortality (censored at Day 90) and survival time to Day 90 (censored at hospital discharge).
  
  
  CONCLUSIONS
  The trial will determine whether active temperature control reduces body temperature compared with standard care. It is primarily being conducted to establish whether a phase III trial with a patient-centred end point of Day 90 mortality is justified and feasible.
authors.affiliation: Intensive Care Unit, Wellington Regional Hospital, Wellington, New Zealand. paul.young@ccdhb.org.nz.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Young
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bailey
authors.affiliation: Medical Research Institute of New Zealand, Wellington, New Zealand.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Beasley
authors.affiliation: Medical Research Institute of New Zealand, Wellington, New Zealand.
authors.forename: Ross C
authors.initials: RC
authors.lastname: Freebairn
authors.affiliation: Critical Care Division, The George Institute for Global Health, Sydney, NSW, Australia.
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Hammond
authors.affiliation: Intensive Care Unit, The Canberra Hospital, Canberra, ACT, Australia.
authors.forename: Frank M P van
authors.initials: FM
authors.lastname: Haren
authors.affiliation: Critical Care Division, The George Institute for Global Health, Sydney, NSW, Australia.
authors.forename: Meg L
authors.initials: ML
authors.lastname: Harward
authors.affiliation: Intensive Care Unit, Christchurch Hospital, Christchurch, New Zealand.
authors.forename: Seton J
authors.initials: SJ
authors.lastname: Henderson
authors.affiliation: Medical Research Institute of New Zealand, Wellington, New Zealand.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Mackle
authors.affiliation: Medical Research Institute of New Zealand, Wellington, New Zealand.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: McArthur
authors.affiliation: Medical Research Institute of New Zealand, Wellington, New Zealand.
authors.forename: Shay P
authors.initials: SP
authors.lastname: McGuinness
authors.affiliation: Critical Care Division, The George Institute for Global Health, Sydney, NSW, Australia.
authors.forename: John A
authors.initials: JA
authors.lastname: Myburgh
authors.affiliation: Critical Care Division, The George Institute for Global Health, Sydney, NSW, Australia.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Saxena
authors.affiliation: Medical Research Institute of New Zealand, Wellington, New Zealand.
authors.forename: Anne
authors.initials: A
authors.lastname: Turner
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Steve A R
authors.initials: SA
authors.lastname: Webb
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
mesh_terms: D002985:Clinical Protocols; D005334:Fever / Q000517:prevention & control / Q000628:therapy*; D006801:Humans; D007362:Intensive Care Units; D012107:Research Design