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

A

Assistance Publique - Hôpitaux de Paris

Status

Enrolling

Conditions

Supraventricular Arrhythmia
Septic Shock

Treatments

Procedure: Rhythm control strategy:
Procedure: Risk control strategy
Procedure: Rate control strategy:

Study type

Interventional

Funder types

Other

Identifiers

NCT04844801
APHP190070

Details and patient eligibility

About

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. 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 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.

Full description

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 will be proposed to the patient. If the patient is unable to give his/her consent, the informed consent of the next-of-kin will be sought by study investigator. In the case the next-of-kins 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.

Enrollment

240 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

  1. Age >= 18 years

  2. Septic shock, 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 to maintain the MAP > 65 mmHg
  3. NOSVA with heart rate ≥ 110 bpm lasting 5 minutes or more

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

  5. Affiliation to a social security system

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

240 participants in 3 patient groups

Risk control strategy
Active Comparator group
Description:
Magnesium sulfate + control of the modifiable NOSVA risk factors
Treatment:
Procedure: Risk control strategy
Rate control strategy
Active Comparator group
Description:
Risk-control + "low-dose" amiodarone
Treatment:
Procedure: Rate control strategy:
Rhythm control strategy
Active Comparator group
Description:
Risk-control + "high-dose" amiodarone +/- electrical cardioversion
Treatment:
Procedure: Rhythm control strategy:

Trial contacts and locations

1

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Central trial contact

Vincent LABBE, MD

Data sourced from clinicaltrials.gov

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