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

2019 unpublished
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
more » ... ol. 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. and diastolic function in septic shock. Intensive care medicine 1997, 23(5):553-560. Sepsis: a Cohort Study. Am J Respir Crit Care Med 2016. 5. Kuipers S KKP, Cremer OL: Incidence, risk factors and outcomes of new-onset atrial fibrillation in patients with sepsis: a systematic review. Crit Care 2014, 18(6):688. 6. Arrigo M, Bettex D, Rudiger A: Management of atrial fibrillation in critically ill patients. Critical care research and practice 2014, 2014:840615. 7. Prognostic impact of restored sinus rhythm in patients with sepsis and newonset atrial fibrillation. Crit Care 2016, 20(1):373. 8. Balik M: New-onset atrial fibrillation in critically ill patients -Implications for rhythm rather than rate control therapy? International journal of cardiology 2018, 266:147-148. 9. Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, Bourassa MG, Arnold JM, Buxton AE, Camm AJ et al: Rhythm control versus rate control for atrial fibrillation and heart failure. The New England journal of medicine 2008, 358(25):2667-2677. 10. Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, Said SA, Darmanata JI, Timmermans AJ, Tijssen JG et al: A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. The New England journal of medicine 2002, 347(23):1834-1840. 11. Investigators. AFADS: Maintenance of sinus rhythm in patients with atrial fibrillation: an AFFIRM substudy of the first antiarrhythmic drug. Journal of the American College of Cardiology 2003, 42(1):20-29. 12. Marchese P, Bursi F, Delle Donne G, Malavasi V, Casali E, Barbieri A, Melandri F, Modena MG: Indexed left atrial volume predicts the recurrence of non-A, D'Ippoliti F, Raffone C, Venditti M, Guarracino F, Girardis M, Tritapepe L, Pietropaoli P, Mebazaa A, Singer M.: Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA 2013, 310(16):1683-1691. 18. Balik M RJ, Leden P, Zakharchenko M, Otahal M, Bartakova H, Korinek J: Concomitant use of beta-1 adrenoreceptor blocker and norepinephrine in patients with septic shock. Wien Klin Wochenschr 2012, 124:552-556. 19. Balik M RJ, Leden P, Zakharchenko M, Otahal M, Bartakova H, Korinek J: Concomitant 20 use of beta-1 adrenoreceptor blocker and norepinephrine in patients with septic shock. Reply to a letter to the authors. Wien Klin Wochenschr 2014, 126(7-8):246-247. 20. McLean AS TF, Vieillard-Baron A: Beta-blockers in septic shock to optimize hemodynamics? No. Intensive Care Med 2016. 21. Echt DS LP, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL, et al.: Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. NEJM 1991, 324(12):781-788. 22. Arrigo M BD, Rudiger A: Management of atrial fibrillation in critically ill patients. Crit Care Res Pract 2014, 2014(840615). 23. Kirchhof P AB, Darius H, De Caterina R, Le Heuzey JY, Schilling RJ, Schmitt J, Zamorano JL.: Management of atrial fibrillation in seven European countries after the publication of the 2010 ESC Guidelines on atrial fibrillation: primary results of the PREvention oF thromboemolic events--European Registry in Atrial Fibrillation (PREFER in AF). Europace 2014, 16(1):6-14. 24. Sleeswijk ME VNT, Tulleken JE, Ligtenberg JJ, Girbes AR, Zijlstra JG: Clinical review: treatment of new-onset atrial fibrillation in medical intensive care patientsa clinical framework. Crit Care 2007, 11(6):233. 25. Arrigo M JN, Seifert B, Spahn DR, Bettex D, Rudiger A.: Disappointing Success of Electrical Cardioversion for New-Onset Atrial Fibrillation in Cardiosurgical ICU Patients. Crit Care Med 2015, 43(11):2354-2359. 26. Hassan S, Ayoub W, Hassan M, Wisgerhof M: Amiodarone-induced myxoedema coma. BMJ case reports 2014, 2014. 27. Hofmann A NC, Ofluoglu S, Holzmannhofer J, Strohmer B, Pirich C: Incidence and reappraisal? Intensive care medicine 2000, 26(12):1730-1739. 33. Papiris SA, Triantafillidou C, Kolilekas L, Markoulaki D, Manali ED: Amiodarone: review of pulmonary effects and toxicity. Drug safety 2010, 33(7):539-558. 34. Antiarrhythmic drug use in patients <65 years with atrial fibrillation and without structural heart disease. The American journal of cardiology 2015, 115(3):316-322. 35.
doi:10.21203/rs.2.312/v1 fatcat:t3xwnwfjsferdnvrenjkscfkli