Rate, Rhythm or Risk Control for New-onset Supraventricular Arrhythmia During Septic Shock: a Randomized Controlled Trial
Rate, Rhythm or Risk Control for New-onset Supraventricular Arrhythmia During Septic Shock: a Randomized Controlled Trial
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 cardioversion, and (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. Rate control, would limit potential adverse
 events of high dose of amiodarone and of electrical cardioversion, while controlling
 haemodynamics. Therefore, it seems important to compare these three strategies.

 Our hypothesis is dual: first, that 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.
All consecutive adult patients admitted to the intensive care unit with NOSVA during septic
 shock will be included in the presence of inclusion criteria and in the absence of exclusion
 criteria.

 Randomization, performed immediately after the inclusion (Day-1), in 1:1:1 ratio will be
 stratified on center. Then the patient will receive the randomized strategy: risk control,
 rate control or rhythm control.

 Before inclusion, the informed consent of the next-of-kin will be sought by study
 investigator because the patient will be unable to express his/her will. In the case the
 next-of-kin are unidentified and/or unreachable, an emergency procedure will be applied.
 Patient consent will be sought as soon as their state of health allows it.

 According to clinical guidelines, patients in all groups will receive therapeutic
 anticoagulation if NOSVA > 48 hours and in the absence of contraindication. In all groups,
 recommendations for the management of septic shock will be followed.

 After day-7 (or hospital discharge if before J7), NOSVA treatment will be left at the
 discretion of attending physicians.

 Evaluation criteria will be collected at day-2, day-3, day-7 (or at hospital discharge if
 before day-7), at the day of ICU discharge and at Day-28. If the patient has been discharged
 before Day-28, the vital status may be obtained by phone call at Day-28.
Inclusion Criteria:

 1. Age >= 18 years

 2. Septic shock since a maximum of 72 hours, defined by the association of the following
 criteria:

 Documented or suspected infection, with initiation of antibiotic therapy Initiation of
 vasopressors (norepinephrine, epinephrine) for at least 1 hour and at most 72 hours

 3. Invasive mechanical ventilation

 4. NOSVA with heart rate ≥ 110 bpm lasting 5 minutes or more

 5. Written informed consent (patient, next of skin or emergency situation)

 6. Affiliation to a social security system

 Exclusion Criteria:

 Exclusion Criteria :

 1. Refractory shock defined by a dose of noradrenaline BASE or adrenaline BASE > 1.2
 µg/kg/min

 2. Cardiac surgery or cardiac transplant in the previous month

 3. Aortic or mitral mechanical prosthesis, significant mitral stenosis (mitral surface <
 1.5 cm2)

 4. Congenital heart disease other than bicuspid aortic valve, atrial defect or patent
 foramen ovale.

 5. History of supraventricular arrhythmia before septic shock

 6. NOSVA lasting at most 36 hrs (or 24 hrs with vasopressors)

 7. Electrical cardioversion or use of amiodarone, other antiarrhythmic, or drug inducing
 bradycardia (beta-blockers, bradycardic calcium channel blocker, digitalis,
 flécaïnamide) in the previous 6 hours before inclusion

 8. Contraindication to amiodarone: history of serious adverse event related to
 amiodarone, history of lung disease related to amiodarone, history of hyperthyroidism
 related to amiodarone, PR interval > 240 ms, severe sinus node dysfunction with no
 pacemaker, 2°/ 3° atrioventricular block with no pacemaker, QTc>480 ms, known or
 treated hyperthyroidism, hypersensitivity to iodine, amiodarone or to any of the
 excipients, severe hepatocellular insufficiency (prothrombin rate <20%), diffuse
 Interstitial Lung Disease.

 9. Kalemia < 3 mmol/L

 10. Pregnant or breast feeding women

 11. Moribund patient or death expected from underlying disease during the current
 admission; Patient deprived of liberty and persons subject to institutional
 psychiatric care

 12. Participation to another interventional trial on septic shock and/or arrhythmic
 disease