Propafenone Versus Amiodarone in Septic Shock (PRASE)

Prospective Randomized Study of Efficacy and Safety of 1c Class Antiarrhythmic Agent (Propafenone) in Septic Shock

Arrhythmias accompany septic shock in increased rates than in other ICU cohorts and their presence and management are related to patient´s prognosis. 1c class antiarrhythmics are seldom administered in intensive care due to a dose dependent toxicity published in case reports and unfavourable outcome reported in a few prospective trials done on cardiology patients. The papers on 1c class antiarrhythmics do not take into consideration a complex haemodynamic assessment using echocardiography. The authors have recently presented a retrospective study on SV arrhythmias in septic shock patients demonstrating favourable effect and safety of propafenone which showed higher antiarrhythmic efficacy than amiodarone.

Study Overview

• Status: Completed
• Conditions: Septic Shock; Supraventricular Arrhythmia
• Intervention / Treatment: Drug: Propafenone i.v.; Drug: Amiodarone i.v.

Detailed Description

Primary aim is to verify the conclusions of the retrospective study, i.e. efficacy and safety of propafenone, in a prospective blinded randomized trial performed in two large intensive care units. Secondary aims are to monitor the electromechanics of left atrium in patients with SV arrhythmias in septic shock.

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 4

Contacts and Locations

Study Locations

• Czechia
  • Prague 10, Czechia, 100 34
    • Dept. Anaesthesia and Intensive Care, 3rd Medical Faculty, Charles University
  • Prague 2, Czechia, 128 08
    • Dept of Anaesthesia and Intensive Care, General University Hospital, 1st Medical Faculty, Charles University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Septic shock with a new onset SV arrhythmia
• LV systolic function normal to moderately reduced according to echocardiography.

Exclusion Criteria:

• Severe LV systolic dysfunction
• More than 1st degree AV block
• High dose vasopressor therapy with continuous noradrenaline > 1.0 ug/kg.min
• Known intolerance to amiodarone or propafenone
• Absence of septic shock
• Chronic AF
• Dependence on pacemaker
• Status after MAZE procedure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Propafenone i.v.; Patients in septic shock with a new onset supraventricular arrhythmia are randomized either to arm treated with propafenone or with amiodarone. Both arms will have standard treatment, there are no limits to indicated electric cardioversion as part of treatment. Intervention: Bolus of 35-70 mg intravenous propafenone followed by continuous infusion of 400-840 mg/24h.	Drug: Propafenone i.v.; Treatment; Other Names: Antiarrhythmic therapy
Active Comparator: Amiodarone i.v.; Patients in septic shock with a new onset supraventricular arrhythmia are randomized either to arm treated with propafenone or with amiodarone. Both arms will have standard treatment, there are no limits to indicated electric cardioversion as part of treatment. Intervention: Bolus of 150-300 mg of intravenous amiodarone followed by continuous infusion of 600-1800 mg/24h.	Drug: Amiodarone i.v.; Treatment; Other Names: Antiarrhythmic therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of propafenone	cardioversion rate	1 year
ICU mortality of septic shock patients on propafenone for a SV arrhythmia	ICU mortality	1 year
28-day mortality of septic shock patients on propafenone for a SV arrhythmia	28-day mortality	2 years
12-month mortality of septic shock patients on propafenone for a SV arrhythmia	12-month mortality	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electromechanics of left atrium	left atrial emptying	1 year
Electromechanics of LA	isovolumic and ejection times	1 year

Collaborators and Investigators

• Sponsor: Charles University, Czech Republic
• Investigators: Principal Investigator: Martin Balik, A/Prof, Dept of Anaesthesia and Intensive Care

Publications and helpful links

General Publications

• Balik M, Waldauf P, Maly M, Matousek V, Brozek T, Rulisek J, Porizka M, Sachl R, Otahal M, Brestovansky P, Svobodova E, Flaksa M, Stach Z, Pazout J, Duska F, Smid O, Stritesky M. Efficacy and safety of 1C class antiarrhythmic agent (propafenone) for supraventricular arrhythmias in septic shock compared to amiodarone: protocol of a prospective randomised double-blind study. BMJ Open. 2019 Sep 3;9(9):e031678. doi: 10.1136/bmjopen-2019-031678.

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2017
• Primary Completion (Actual): July 4, 2022
• Study Completion (Actual): August 1, 2022

Study Registration Dates

• First Submitted: December 7, 2016
• First Submitted That Met QC Criteria: January 20, 2017
• First Posted (Estimate): January 24, 2017

Study Record Updates

• Last Update Posted (Actual): August 2, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Septic shock; Intensive Care; Amiodarone; Propafenone; Supraventricular Arrhythmia
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Arrhythmias, Cardiac; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Potassium Channel Blockers; Amiodarone; Anti-Arrhythmia Agents; Propafenone
• Other Study ID Numbers: 1691/16 S-IV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No