Effect of High-Flow Nasal Therapy on Patient-Centred Outcomes in Patients at High Risk of Postoperative Pulmonary Complications After Cardiac Surgery: A Statistical Analysis Plan for NOTACS, a Multicentre Adaptive Randomised Controlled Trial.

Abstract BackgroundThe NOTACS trial will assess the efficacy, safety and cost-effectiveness of high-flow nasal therapy (HFNT) compared to standard oxygen therapy (SOT) on the outcomes of patients after cardiac surgery. Methods / DesignNOTACS is an adaptive, international, multicentre, parallel group, randomised controlled trial, with a pre-planned interim sample size re-estimation (SSR). A minimum of 850 patients will be randomised 1:1 to receive either HFNT or SOT. The primary outcome is days alive and at home in the first 90 days after the planned surgery (DAH90), with a number of secondary analyses and cost-effectiveness analyses also planned. The interim SSR will take place after a minimum of 300 patients have been followed up for 90 days and will allow for the sample size to increase up to a maximum of 1152 patients. DiscussionThis manuscript outlines the key features of the NOTACS statistical analysis plan, and was submitted to the journal before the interim analysis in order to preserve scientific integrity under an adaptive design framework. The NOTACS SAP closely follows published guidelines for the content of SAPs in clinical trials. Trial registration: ISRCTN14092678 (13th May 2020, https://www.isrctn.com/ISRCTN14092678)