Prospective randomized double-blind study of efficacy and safety of 1c class antiarrhythmic agent (propafenone) for supraventricular arrhythmias in septic shock compared to amiodarone

Abstract

Background: Septic shock often leads to supraventricular arrhythmias which contribute to haemodynamic compromise. A large retrospective study in this population generated the hypothesis that propafenone could be more effective than amiodarone in achieving and maintaining sinus rhythm in new-onset supraventricular arrhythmia. Moreover, the success of cardioversion can be predicted by certain echocardiographic parameters, which can guide the decision whether to aim for rhythm or rate control. Methods: A prospective double-blind multi-center randomized controlled trial includes patients with new-onset arrhythmia related to septic shock (2016 definition), but without severe impairment of the left ventricular ejection fraction. After baseline echocardiography, the patient will be randomised to receive a bolus and maintenance dose of either amiodarone or propafenone. The primary outcome is the proportion of patients that have achieved rhythm control at 24 hours after the start of the infusion. The secondary outcomes are the composite percentage of patients that needed rescue treatments (DC cardioversion or unblinding and cross over of the antiarrhythmics) within 24 hours, recurrence of arrhythmias, ICU mortality, 28-day and 1-year mortality. In the post-hoc analysis we plan to separately assess subgroups of patients with pulmonary hypertension and right ventricular dysfunction without left ventricular systolic dysfunction. In the exploratory part of the study we will assess whether (1.) the presence of a transmitral diastolic A wave and its higher velocity-time integral is predictive for the sustainability of mechanical sinus rhythm and whether (2.) the indexed left atrial endsystolic volume is predictive of recurrent arrhythmia. Discussion: Amiodarone has become the first-line agent of use in almost any tachyarrhythmia in the critically ill. Nevertheless, it has a wide range of side effects and may not be the most effective drug in all circumstances. In light of this, we designed a prospective randomised controlled trial. Considering that in the observational study the restoration of sinus rhythm within 24h occurred in 74% of the amiodarone-treated patients and in 89% of patients treated with propafenone, we plan to include 200 patients to have an 80% chance to demonstrate the superiority of propafenone at p=0.05. Assuming a 10% dropout, we plan to randomize 220 patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03029169, registered on 24.1.2017. Keywords: Supraventricular arrhythmia, septic shock, propafenone, amiodarone, intensive care.

Propafenone versus Amiodarone for Supraventricular Arrhythmias in Septic Shock: A Randomised Controlled Trial

“…1). 80 patients (38.3%) were females, the median BMI was 29(IQR [25][26][27][28][29][30][31][32][33]. 158 patients had atrial brillation (75.6%), 41(19.6%) atrial utter and 10(4.8%) other supraventricular tachycardia.…”

“…The measurement was a standardised ECG gated biplane method in 77 patients (45.3%) and a monoplane measurement in an apical four chamber plane in 93(54.7%). The difference between the biplane method and the monoplane measurement was not signi cant (30)(31)(32)(33)(34)(35)(36)(37)(38) for the biplane vs 33(IQR 26-40) for the monoplane measurement, p = 0.06). Analysis of patients with LAVI ≥ 40 ml/m 2 (both methods, n = 37, 21.8%) demonstrated a better antiarrhythmic effect of amiodarone (p = 0.05, Fig.…”

“…The last follow up visit was performed on the 3rd of March 2023. The trial protocol was registered under clinical trial number NCT03029169 on 24th of January 2017 and published on 3rd of September 2019 [31]. Detailed methodology is presented in ESM 1.…”

“…with and without indexed left atrial end-systolic volume (LAVI) higher than ≥ 40ml/m 2 , b.) with and without moderate to severe right ventricular (RV) dysfunction (moderate-to-severe RV dilatation with tricuspid antero-posterior systolic excursion (TAPSE) < 15 mm and pulmonary hypertension de ned as pulmonary artery systolic pressure (PAPs) > 40 mmHg) [31].…”

“…The entry parameters for sample size analysis were estimated by the probabilities of cardioversion of 75% for the amiodarone group and 90% for the propafenone group within 24h from the onset of arrhythmia, randomisation ratio 1:1, p = 0.05 and power 0.8. To achieve a statistically signi cant difference under these conditions 100 patients needed to be included into each group, altogether 200 patients were recruited into the trial with an anticipated drop-out of 10% [31].…”