Abstract
Background: The Prophylactic hypOthermia to Lessen trAumatic bRain injury-Randomised Controlled Trial (POLAR-RCT) will evaluate whether early and sustained prophylactic hypothermia delivered to patients with severe traumatic brain injury improves patient-centred outcomes. Methods: The POLAR-RCT is a multicentre, randomised, parallel group, phase III trial of early, prophylactic cooling in critically ill patients with severe traumatic brain injury, conducted in Australia, New Zealand, France, Switzerland, Saudi Arabia and Qatar. A total of 511 patients aged 18-60 years have been enrolled with severe acute traumatic brain injury. The trial intervention of early and sustained prophylactic hypothermia to 33 °C for 72 h will be compared to standard normothermia maintained at a core temperature of 37 °C. The primary outcome is the proportion of favourable neurological outcomes, comprising good recovery or moderate disability, observed at six months following randomisation utilising a midpoint dichotomisation of the Extended Glasgow Outcome Scale (GOSE). Secondary outcomes, also assessed at six months following randomisation, include the probability of an equal or greater GOSE level, mortality, the proportions of patients with haemorrhage or infection, as well as assessment of quality of life and health economic outcomes. The planned sample size will allow 80% power to detect a 30% relative risk increase from 50% to 65% (equivalent to a 15% absolute risk increase) in favourable neurological outcome at a two-sided alpha of 0.05. Discussion: Consistent with international guidelines, a detailed and prospective analysis plan has been developed for the POLAR-RCT. This plan specifies the statistical models for evaluation of primary and secondary outcomes, as well as defining covariates for adjusted analyses and methods for exploratory analyses. Application of this statistical analysis plan to the forthcoming POLAR-RCT trial will facilitate unbiased analyses of these important clinical data.
| Original language | English |
|---|---|
| Article number | 259 |
| Number of pages | 10 |
| Journal | Trials |
| Volume | 19 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 27 Apr 2018 |
Keywords
- Cooling
- Critical care
- Hypothermia
- Outcome
- Randomised controlled trials
- Traumatic brain injury
Cite this
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Statistical analysis plan for the POLAR-RCT : The Prophylactic hypOthermia trial to Lessen trAumatic bRain injury-Randomised Controlled Trial. / Presneill, Jeffrey; Gantner, Dashiell; Nichol, Alistair; McArthur, Colin; Forbes, Andrew; Kasza, Jessica; Trapani, Tony; Murray, Lynnette; Bernard, Stephen; Cameron, Peter; Capellier, Gilles; Huet, Olivier; Newby, Lynette; Rashford, Stephen; Rosenfeld, Jeffrey V.; Smith, Tony; Stephenson, Michael; Varma, Dinesh; Vallance, Shirley; Walker, Tony; Webb, Steve; James Cooper, D.
In: Trials, Vol. 19, No. 1, 259, 27.04.2018.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Statistical analysis plan for the POLAR-RCT
T2 - The Prophylactic hypOthermia trial to Lessen trAumatic bRain injury-Randomised Controlled Trial
AU - Presneill, Jeffrey
AU - Gantner, Dashiell
AU - Nichol, Alistair
AU - McArthur, Colin
AU - Forbes, Andrew
AU - Kasza, Jessica
AU - Trapani, Tony
AU - Murray, Lynnette
AU - Bernard, Stephen
AU - Cameron, Peter
AU - Capellier, Gilles
AU - Huet, Olivier
AU - Newby, Lynette
AU - Rashford, Stephen
AU - Rosenfeld, Jeffrey V.
AU - Smith, Tony
AU - Stephenson, Michael
AU - Varma, Dinesh
AU - Vallance, Shirley
AU - Walker, Tony
AU - Webb, Steve
AU - James Cooper, D.
PY - 2018/4/27
Y1 - 2018/4/27
N2 - Background: The Prophylactic hypOthermia to Lessen trAumatic bRain injury-Randomised Controlled Trial (POLAR-RCT) will evaluate whether early and sustained prophylactic hypothermia delivered to patients with severe traumatic brain injury improves patient-centred outcomes. Methods: The POLAR-RCT is a multicentre, randomised, parallel group, phase III trial of early, prophylactic cooling in critically ill patients with severe traumatic brain injury, conducted in Australia, New Zealand, France, Switzerland, Saudi Arabia and Qatar. A total of 511 patients aged 18-60 years have been enrolled with severe acute traumatic brain injury. The trial intervention of early and sustained prophylactic hypothermia to 33 °C for 72 h will be compared to standard normothermia maintained at a core temperature of 37 °C. The primary outcome is the proportion of favourable neurological outcomes, comprising good recovery or moderate disability, observed at six months following randomisation utilising a midpoint dichotomisation of the Extended Glasgow Outcome Scale (GOSE). Secondary outcomes, also assessed at six months following randomisation, include the probability of an equal or greater GOSE level, mortality, the proportions of patients with haemorrhage or infection, as well as assessment of quality of life and health economic outcomes. The planned sample size will allow 80% power to detect a 30% relative risk increase from 50% to 65% (equivalent to a 15% absolute risk increase) in favourable neurological outcome at a two-sided alpha of 0.05. Discussion: Consistent with international guidelines, a detailed and prospective analysis plan has been developed for the POLAR-RCT. This plan specifies the statistical models for evaluation of primary and secondary outcomes, as well as defining covariates for adjusted analyses and methods for exploratory analyses. Application of this statistical analysis plan to the forthcoming POLAR-RCT trial will facilitate unbiased analyses of these important clinical data.
AB - Background: The Prophylactic hypOthermia to Lessen trAumatic bRain injury-Randomised Controlled Trial (POLAR-RCT) will evaluate whether early and sustained prophylactic hypothermia delivered to patients with severe traumatic brain injury improves patient-centred outcomes. Methods: The POLAR-RCT is a multicentre, randomised, parallel group, phase III trial of early, prophylactic cooling in critically ill patients with severe traumatic brain injury, conducted in Australia, New Zealand, France, Switzerland, Saudi Arabia and Qatar. A total of 511 patients aged 18-60 years have been enrolled with severe acute traumatic brain injury. The trial intervention of early and sustained prophylactic hypothermia to 33 °C for 72 h will be compared to standard normothermia maintained at a core temperature of 37 °C. The primary outcome is the proportion of favourable neurological outcomes, comprising good recovery or moderate disability, observed at six months following randomisation utilising a midpoint dichotomisation of the Extended Glasgow Outcome Scale (GOSE). Secondary outcomes, also assessed at six months following randomisation, include the probability of an equal or greater GOSE level, mortality, the proportions of patients with haemorrhage or infection, as well as assessment of quality of life and health economic outcomes. The planned sample size will allow 80% power to detect a 30% relative risk increase from 50% to 65% (equivalent to a 15% absolute risk increase) in favourable neurological outcome at a two-sided alpha of 0.05. Discussion: Consistent with international guidelines, a detailed and prospective analysis plan has been developed for the POLAR-RCT. This plan specifies the statistical models for evaluation of primary and secondary outcomes, as well as defining covariates for adjusted analyses and methods for exploratory analyses. Application of this statistical analysis plan to the forthcoming POLAR-RCT trial will facilitate unbiased analyses of these important clinical data.
KW - Cooling
KW - Critical care
KW - Hypothermia
KW - Outcome
KW - Randomised controlled trials
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=85046128909&partnerID=8YFLogxK
U2 - 10.1186/s13063-018-2610-y
DO - 10.1186/s13063-018-2610-y
M3 - Article
VL - 19
JO - Trials
JF - Trials
SN - 1745-6215
IS - 1
M1 - 259
ER -