Rate, Rhythm or Risk Control for New-onset Supraventricular Arrhythmia During Septic Shock: a Randomized Controlled Trial

Summary

New-onset supraventricular arrhythmia (NOSVA) is reported in 40 % of patients with septic shock and is associated with hemodynamic alterations and mortality. The lack of consensus regarding best practices for the management of NOSVA in this setting has led to major variations in practice patterns. Observational studies reported three usual strategies: (i) heart rate control (hereafter rate control) with the use of antiarrhythmic drugs, essentially based on low dose of amiodarone, (ii) rhythm control with the use of antiarrhythmic drugs, essentially based on high dose of amiodarone, and electrical cardioversionand (iii) modifiable NOSVA risk factors control (hereafter risk control) without using antiarrhythmic drugs.

Risk control would minimize adverse events of antiarrhythmic drugs. Rhythm control would rapidly improve haemodynamics via restoring diastole and decreasing cardiac metabolic demand, while minimizing exposure to anticoagulation. Heart-Rate control, would limit potential adverse events of high dose of amiodarone and of electrical cardioversion (only in patients intubated on mechanical ventilation), while controlling haemodynamics. Therefore, it seems important to compare these three strategies.

Our hypothesis is dual: first, that heart-rate control and rhythm control each improve hemodynamics with in fine a decreased mortality, as compared to a risk control; second, that rhythm control outperforms rate control in this setting.

This is a multicenter, parallel-group, open-label, randomized controlled superiority trial to compare the effectiveness and safety of these three strategies (risk control, rate control and rhythm control) for NOSVA during septic shock.

Conditions

• Supraventricular Arrhythmia
• Septic Shock

Interventions

PROCEDURE

Risk control strategy

* Magnesium sulfate 2g intravenous bolus over 20 mn (if creatinine clearance \>30 mL/min) * Control of the modifiable NOSVA risk factors: hypovolemia, sepsis, metabolic disorders (e.g., hypokalemia, hyponatremia), acidosis, hypoxia, excess cardiac inotropism of vasopressors, central venous catheter malposition, hyperthermia.

PROCEDURE

Heart-Rate control strategy:

* Risk-control as described above * "Low dose" amiodarone: * Intravenous loading bolus (day-1): bolus of 4 mg/kg IV over 1hour (maximum 300 mg IV over 1 hour ) * Enteral maintenance dose (oral or via gastric tube) (day-1 to day-7) 200mg/24hour in a single dose for 7 days (150 mg intravenous over 1hour if enteral route is unavailable)

PROCEDURE

Rhythm control strategy:

* Risk control as described above * "High dose" amiodarone: * Intravenous loading dose (day-1): initial bolus 7 mg/kg over 1 hour (maximum 600 mg i.e. 4 IVL vials over 1 hour); followed by continuous intravenous maintenance: for a total of 1200 mg over the first 24 hours (infusion pump) * Enteral dose maintenance Day-2 and day-3: 1200 mg/ 24 hours in three doses for 48hours (720 mg continuous intravenous over 24 hours if enteral route is unavailable). Day-4 to day-7: 200 mg/24 hours once a day (150 mg intravenous over 1hourr if enteral route is unavailable) - Electrical cardioversion (only in patients intubated on mechanical ventilation) 1 to 3 external electric shocks starting at 200J if: * NOSVA persists after initial bolus of amiodarone AND norepinephrine base (or epinephrine base) doses \> 0.3 µg/kg/min; * NOSVA persists more than 6 hours after initial IV loading dose of amiodarone. NB: Beyond day 7 (or after discharge from intensive care if this occurs before da

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Vincent LABBE, MD · Assistance Publique - Hôpitaux de Paris

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-11-09

Primary Completion

2026-02-28

Completion

2026-03-31

Countries

• France

Study Locations