Risk, rate or rhythm control for new onset supraventricular arrhythmia during septic shock: protocol for the CAFS multicentre, parallel-group, open-label trial

Abstract

Introduction: New-onset supraventricular arrhythmia (NOSVA) is the most common arrhythmia in patients with septic shock and is associated with haemodynamic alterations and increased mortality rates. With no data available from randomised trials, clinical practice for patient management varies widely. In this setting, rate control or rhythm control could be beneficial in limiting the duration of shock and preventing evolution to multiorgan dysfunction.

Methods and analysis: The Control Atrial Fibrillation in Septic shock (CAFS) study is a binational (French and Belgium), multicentre, parallel-group, open-label, randomised controlled superiority trial to compare the efficacy and safety of three management strategies in patients with NOSVA during septic shock. The expected duration of patient enrolment is 42 months, starting from November 2021. Patients will be randomised to receive either risk control (magnesium and control of risk factors for NOSVA), rate control (risk control and low dose of amiodarone) or rhythm control (risk control and cardioversion using high dose of amiodarone with external electrical shock if NOSVA persists) for 7 days. Patients with a history of SVA, NOSVA lasting more than 48 hours, recent cardiac surgery or a contraindication to amiodarone will not be included. We plan to recruit 240 patients. Patients will be randomised on a 1:1:1 basis and stratified by centre. The primary endpoint is a hierarchical criterion at day 28 including all-cause mortality and the duration of septic shock defined as time from randomisation to successful weaning of vasopressors. Secondary outcomes include: individual components of the primary endpoint; arterial lactate clearance at day 3; efficacy at controlling cardiac rhythm at day 7; proportion of patients free from organ dysfunction at day 7; ventricular arrhythmia, conduction disorders, thrombotic events, major bleeding events and acute hepatitis related to amiodarone at day 28; intensive care unit and hospital lengths of stay at day 28.

Ethics and dissemination: The study has been approved by the French (Comité Sud-Ouest et Outre-Mer II, France, registration number 2019-A02624-53) and Belgian (Comité éthique de l'hôpital Erasme, Belgium, registration number CCB B4062023000179) ethics committees. Patients will be included after obtaining signed informed consent. The results will be submitted for publication in peer-reviewed journals.

Trial registration number: NCT04844801.

Keywords: Adult intensive & critical care; Cardiovascular Disease; Clinical Protocols; INFECTIOUS DISEASES.

Figure 1. Study schema. D, day; ICU, intensive care unit; IV, intravenous; Mg2+, magnesium; NOSVA, new-onset supraventricular arrhythmia. * If NOSVA > 48h, the patient can still be included if transoesophageal echocardiography (under mechanical ventilation) excludes intracardiac thrombus and the patient can receive therapeutic anticoagulation.

Figure 2. Schema of strategies for each group according to the evolution of the randomised patients. EES, external electrical shock; NOSVA, new-onset supraventricular arrhythmia.