A randomised controlled trial to investigate clinical and cost effectiveness of Amiodarone vs Beta Blockade for new onset atrial fibRillation in icU - a Pragmatic sTudy (ABBRUPT)

RESEARCH QUESTION: In adult intensive care (ICU) patients with new onset atrial fibrillation (NOAF), what is the clinical and cost effectiveness of amiodarone versus beta blockade? BACKGROUND: NOAF in ICU is common, generally short-lived, tends to occur when the patient is at their sickest but at the time, relatively easily treated. However NOAF is associated with increased in-hospital and 90-day mortality (1, 2), ICU and hospital stay (3, 4) and life-changing complications such as stroke, thromboembolic events or myocardial infarction (MI) even once the patient has left the ICU (5). A retrospective analysis of NOAF from the large MIMIC dataset (1) reported that beta blocker treatment was associated with a reduction in 90-day mortality whereas amiodarone was associated with increased mortality. However, a combined analysis of MIMIC and PICRAM databases (6) found no difference in hospital mortality but did not report longer term outcomes. The majority of intensivists worldwide (7) prefer amiodarone but there is a paucity of evidence on which is the most effective AF management. The finding of increased mortality associated with amiodarone and the lack of evidence means that there is an urgent need to understand how best to manage this common condition. AIMS AND OBJECTIVES: To conduct a multi-centre, randomised trial to compare two commonly used treatments for NOAF in ICU. To perform clinical and full economic evaluation to compare treatment with beta blockers and amiodarone. METHODS: Multicentre, pragmatic, open label, parallel group allocation concealed randomised controlled with economic evaluation. Patients with NOAF (defined as AF lasting 30 minutes in patients not previously known to have AF) randomised to receive either beta blocker (bisoprolol, metoprolol or esmolol) or amiodarone. The primary outcome will be survival at 90 days with secondary outcomes of cost-effectiveness of the interventions, ICU / hospital mortalities, ICU / hospital length of stay, rates of stroke and MI, rate of established AF by the end of ICU stay / death. TIMELINES FOR DELIVERY: Months 1-6: set-up; 7-42: recruitment (with embedded 9-month pilot); 42-45: 90-day follow-up; 45-51: data cleaning, analysis, close out and publication ANTICIPATED IMPACT AND DISSEMINATION: Of ICU doctors, amiodarone treatment is used by 45% and beta blockers 23% for AF worldwide (7). Should ABBRUPT demonstrate superiority for one treatment over the other, it will curtail inferior management of a significant number of ICU patients. Late death and adverse cardiovascular events such as stroke and MI are an important but often overlooked legacy of surviving ICU. These are much more common when the patient has had NOAF during their critical illness. This trial will provide evidence about the most effective way to prevent long term sequalae and death following NOAF in ICU. We will disseminate our findings through live presentation of the results at an international meeting (such as criticalcarereviews.com) and social media, simultaneously with publication in a leading medical journal. We will work with our PPI and the Intensive Care Society to develop clinical guidelines to accelerate implementation of the findings in clinical practice. Our PPI will also disseminate the trial findings to interested partners. AF in ICU is so common and both beta blockers and amiodarone relatively inexpensive drugs, that many healthcare systems worldwide will implement the findings of ABBRUPT.