Nasal Oxygen Therapy After Cardiac Surgery (NOTACS): Effect of high-flow nasal therapy on patient-centred outcomes in patients at high risk of postoperative pulmonary complications after cardiac surgery. A multicentre randomised controlled trial.

RESEARCH DESIGN The proposed study is an adaptive, multicentre, UK, parallel group, randomised controlled clinical trial with embedded cost-effectiveness analysis comparing use of High Flow Nasal Therapy (HFNT) to standard oxygen therapy in patients at high risk of respiratory complications following cardiac surgery. BACKGROUND Patients undergoing cardiac surgery are at significant risk of postoperative pulmonary complications that may lead to prolonged ICU and hospital stay and increased mortality. HFNT is a non-invasive form of respiratory support. It delivers low level, flow-dependent positive airway pressure and is well tolerated by patients. In a single centre feasibility study prophylactic use of HFNT in cardiac surgical patients at higher risk for pulmonary complications reduced length of hospital stay by 29% (95% CI 11-44%, p=0.012) and intensive care unit (ICU) re-admission rate compared to standard oxygen therapy. AIMS AND OBJECTIVES The primary objectives of the proposed trial are to determine if prophylactic HFNT therapy can result in an increase in the number of Days at Home within the first 90 days after surgery (DAH90) when compared with standard oxygen therapy, and to assess if this is cost effective. Secondary objectives include assessment of postoperative pulmonary complications hospital stays and health related quality of life. METHODS Cardiac surgical patients at higher risk for pulmonary complications will be recruited and randomised to receive either HFNT or standard oxygen therapy. Randomisation will be completed during surgery and will be stratified by centre. Patients will then be extubated according to local standard of care practices and will receive either HFNT or standard oxygen therapy according to their randomised allocation for a minimum of 16 hours post-extubation. Patients will be followed up at 30 days and 90 days post-surgery and will complete a set of quality of life and cost effectiveness questionnaires. The minimum sample size target is 850 participants. The adaptive design will include a sample size re-estimation after 300 patients have been randomised and would allow for a maximum increase in sample size to 1152 patients. This will give us some protection against deviations from original assumptions. The primary analysis will be on the basis of intention-to-treat (ITT). The effects of adherence, attrition, and likely sources of bias, on the primary effect estimate will be evaluated using per protocol, safety and sensitivity analyses respectively. Patients have been actively involved in the design of the study. We undertook 360 degree feedback with participants from our feasibility study and three volunteers (two patients and a next-of-kin) have joined the project team to help write the grant application and sit on the Trial Steering Committee. They have provided advice and clarification on the primary outcome measure and on methods of communicating with patients during consent and follow-up. TIMELINES FOR DELIVERY: January 2020 to December 2023 ANTICIPATED IMPACT AND DISSEMINATION If the findings of our pilot trial are confirmed then the proposed multicentre trial will have significant impact for all UK cardiac surgical centres in terms of both patient outcomes and NHS costs. The aim is to lead to a National Institute of Health and Care Excellence (NICE) review as well as inclusion in national guidelines for cardiac surgical, intensive care and anaesthesia