Statistical analysis plan for early mobilisation by head-up tilt with stepping versus standard care after severe traumatic brain injury – a randomised clinical feasibility trial

Background: Early mobilisation on a tilt table with stepping versus standard care may be beneficial for patients with severe brain injury, but data from randomised clinical trials are lacking. Methods: This statistical analysis plan describes the analyses of data collected in a randomised clinical feasibility trial for early mobilisation by head-up tilt with stepping versus standard care after severe traumatic brain injury. Primary feasibility outcomes are the proportion of included participants who were randomised out of all screened patients; the proportion of participants allocated to the experimental intervention who received at least 60% of the planned exercise sessions; and safety outcomes such as severe adverse events and reactions and adverse events and reactions. Exploratory clinical outcomes are suspected unexpected severe adverse reactions; and functional outcomes as assessed by Coma Recovery Scale – Revised at four weeks; Early Functional Ability Scale, and Functional Independence Measure at three months. Exploratory physiological outcomes are electrocardiographic data; mean arterial pressure; and middle cerebral artery blood flow velocity, all obtained during the head-up tilt test. From the first head-up tilt test and five days onwards, a heart rate was measured by continuous electrocardiography. The detailed description includes the statistical analysis including use of multiple imputation and Trial Sequential Analysis. Conclusions: The present statistical analysis plan serves to minimise potential trial reporting bias and selective P hacking and to improve transparency. This feasibility trial will inform design and eventual launching of a larger multicentre randomised clinical trial. Trial registration: ClinicalTrials.gov identifier: NCT02924649. Registered on 3 October 2016.