Statistical analysis plan for the Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure trial

Abstract

Background: The best sedative medication to reduce delirium, mortality and long term brain dysfunction in mechanically ventilated septic patients is unclear. This multicentre, double-blind, randomised trial investigates the short term and long term effects of dexmedetomidine versus propofol for sedation in mechanically ventilated severely septic patients.Objectives: To describe the statistical analysis plan for this randomised clinical trial comprehensively and place it in the public domain before unblinding.Methods: To ensure that analyses are not selectively reported, we developed a comprehensive statistical analysis plan before unblinding. This trial has an enrolment target of 420 severely septic and mechanically ventilated adult patients, randomly assigned to dexmedetomidine or propofol in a 1:1 ratio. Enrolment was completed in January 2019, and the study was estimated to be completed in September 2019. The primary endpoint is days alive without delirium or coma during first 14 study days. Secondary outcomes include 28-day ventilator-free days, 90-day allcause mortality and cognitive function at 180 days. Time frames all begin on the day of randomisation. All analyses will be conducted on an intention-to-treat basis.Conclusion: This study will compare the effects of two sedatives in mechanically ventilated severely septic patients. In keeping with the guidance on statistical principles for clinical trials, we have developed a comprehensive statistical analysis plan by which we will adhere, as this will avoid bias and support transparency and reproducibility.Trial registration:ClinicalTrials.gov (NCT01739933).