Title: 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.
Funder: Department of Health and Social Care

Abstract: Patients with pre-existing lung conditions undergoing heart surgery are at high risk of postoperative lung complications and often require further respiratory support. They may need a tight-fitting mask to help them breathe and ensure that enough oxygen gets into their blood and carbon dioxide is removed. This treatment is costly, labour intensive and can be uncomfortable. Treatment for lung complications can lead to prolonged hospital stay or even death._x000D_ _x000D_ Recently, there has been increased interest in use of high-flow nasal therapy after cardiac surgery. High-flow nasal therapy (HFNT) provides warmed humidified oxygen (air is warmed and contains some moisture) and has been shown to assist breathing and improve patient recovery. HFNT is comfortable during use and may be even more comfortable than standard treatment with dry oxygen via a face mask or nasal prongs. Without a tight-fitting mask, patients can eat normally and speak freely. _x000D_ _x000D_ In light of this, our group recently investigated whether high-risk patients with certain lung conditions (asthma, chronic obstructive pulmonary disease) or a risk factor for postoperative lung complications (obesity, recent chest infections or heavy smoking) would benefit from routine administration of high-flow nasal therapy immediately after cardiac surgery. We showed that our research design is achievable and that when compared with standard care, the use of HFNT significantly reduced hospital length of stay (by 29%) and was associated with fewer re-admissions to the intensive care unit. _x000D_ _x000D_ This was the first randomised trial to examine the effect of high-flow nasal oxygen therapy compared to standard dry oxygen via nasal prongs on patient-relevant outcomes (length of hospital stay) after open heart surgery in patients at high risk of postoperative lung complications. We hope to expand this trial into numerous other UK centres to see if it can be repeated and whether HFNT should become routine in this patient group after cardiac surgery._x000D_ _x000D_ We presented the study results to patients who participated in our first trial and both clinicians and participants agreed that it is now extremely important to test whether the results can be replicated in a large multicentre study. Several participants have agreed to support the study design and management and two patients have agreed to be co-investigators and join the Trial Steering Committee._x000D_ _x000D_ Following discussion with trial participants it has been decided that the most relevant outcome measure for the trial, from patients’ perspective, is the number of days within the first 90 days after surgery that each patient is alive and able to reside at home (usual residence). This outcome captures more of the patient experience than length of hospital stay as it takes into account patients discharged early who are later re-admitted and patients who are discharged to another care facility after surgery instead of their usual home. It also accounts for late postoperative complications and early death after surgery which is a fairer comparison than length of stay alone._x000D_ _x000D_ To assess the effect of HFNT we will be recruiting a minimum of 850 patients from 10 UK cardiothoracic centres and randomly allocating them to high-flow nasal or standard oxygen therapy, stratifying by centre. Patients will be followed up at 30 days and 90 days after surgery. _x000D_ _x000D_ Results will inform national guidelines for patient intensive care after heart surgery.

Lay abstract: RESEARCH DESIGN_x000D_ 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._x000D_ _x000D_ BACKGROUND_x000D_ 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. _x000D_ _x000D_ AIMS AND OBJECTIVES_x000D_ 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. _x000D_ _x000D_ METHODS_x000D_ 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._x000D_ _x000D_ 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._x000D_ _x000D_ 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._x000D_ _x000D_ 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._x000D_ _x000D_ TIMELINES FOR DELIVERY: January 2020 to December 2023_x000D_ _x000D_ ANTICIPATED IMPACT AND DISSEMINATION_x000D_ 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

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: CARDIOVASCULAR;RESPIRATORY