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

NCT04844801 | Recruiting

• 1 other identifier: APHP190070
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief 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

Septic Shock; Supraventricular Arrhythmia

Keywords

New-onset supraventricular arrhythmia; Atrial fibrillation; Septic shock; Critically ill patient; Strategies; Antiarrhythmic drugs

Outcome Measures

Primary Outcomes (2)

• all-cause mortality (a hierarchical criterion)

  The duration of septic shock is defined as the time (number of days) from randomization to successful weaning of vasopressors The Finkelstein-Schoenfeld method is based on the principle that each patient in the clinical trial is compared with every other patient within each stratum in a pairwise manner. The pairwise comparison proceeds in hierarchical fashion, using all-cause mortality, followed by the duration of septic shock when patients cannot be differentiated on the basis of mortality. This method gives a higher importance to all-cause mortality.

  28 days

• the duration of septic shock according to the Finkelstein-Schoenfeld method (a hierarchical criterion).

  The duration of septic shock is defined as the time (number of days) from randomization to successful weaning of vasopressors The Finkelstein-Schoenfeld method is based on the principle that each patient in the clinical trial is compared with every other patient within each stratum in a pairwise manner. The pairwise comparison proceeds in hierarchical fashion, using all-cause mortality, followed by the duration of septic shock when patients cannot be differentiated on the basis of mortality. This method gives a higher importance to all-cause mortality.

  28 days

Secondary Outcomes (3)

• Rhythm efficacy at day-7 (or at discharge or death if before day-7)

  up to 7 days

• Morbimortality

  Day 28

• Tolerance at day-7 and day-28

  Day 7 and day 28

Study Arms (3)

Risk control strategy

ACTIVE COMPARATOR

Magnesium sulfate + control of the modifiable NOSVA risk factors

Procedure: Risk control strategy

Heart-Rate control strategy

ACTIVE COMPARATOR

Risk-control + "low-dose" amiodarone

Procedure: Heart-Rate control strategy:

Rhythm control strategy

ACTIVE COMPARATOR

Risk-control + "high-dose" amiodarone +/- electrical cardioversion

Procedure: Rhythm control strategy:

Interventions

Risk control strategy PROCEDURE

* 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.

Risk control strategy

Heart-Rate control strategy: PROCEDURE

* 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)

Heart-Rate control strategy

Rhythm control strategy: PROCEDURE

* 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

Rhythm control strategy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years
• 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
• NOSVA with heart rate ≥ 110 bpm lasting 5 minutes or more
• Written informed consent (patient, next of skin or emergency situation)
• Affiliation to a social security system

You may not qualify if:

• Refractory shock defined by a dose of noradrenaline BASE or adrenaline BASE \> 1.2 µg/kg/min
• Cardiac surgery or cardiac transplant in the previous month
• Aortic or mitral mechanical prosthesis, significant mitral stenosis (mitral surface \< 1.5 cm2)
• Congenital heart disease other than bicuspid aortic valve, atrial defect or patent foramen ovale.
• History of supraventricular arrhythmia prior to the episode of septic shock defined by a permanent TRSVN or paroxysmal TRSVN requiring long-term specific treatment (heart rate reducer and/or antiarrhythmic and/or curative anticoagulation) or permanent NOSVA.
• NOSVA that began more than 48 hours ago \* (or more than 24 hours ago under vasopressor). \* In cases of TRSVN dating back more than 48 hours, the patient may be included after undergoing a transesophageal echocardiogram (only in patients who are intubated and on mechanical ventilation) to rule out the presence of an intracardiac thrombus, coupled with the initiation of curative anticoagulation (in the absence of contraindications contraindication) starting from the transesophageal echocardiography.
• 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.
• Kalemia \< 3 mmol/L
• Pregnant or breast feeding women
• Moribund patient or death expected from underlying disease during the current admission; Patient deprived of liberty and persons subject to institutional psychiatric care
• Participation to another interventional trial on septic shock and/or arrhythmic disease

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Service de Médecine Intensive Réanimation-Hôpital Tenon

Paris, 75020, France

RECRUITING

Related Publications (1)

• Labbe V, Desnos C, Preau S, Doyen D, Contou D, Bagate F, Souweine B, Pey V, Bertrand PM, Muller G, Boissier F, Asfar P, Bonnet N, Joffre J, Sy O, Dres M, Annoni F, Monnet X, Carreira S, Vivier E, Serck N, Wiart A, Voicu S, Heming N, Le Breton C, Chevrel G, Chemouni F, Piagnerelli M, Haentjens L, Fartoukh M, Taccone F, Durand D, Monthieux G, Berard L, Rousseau A, Mekontso Dessap A. Risk, rate or rhythm control for new onset supraventricular arrhythmia during septic shock: protocol for the CAFS multicentre, parallel-group, open-label trial. BMJ Open. 2025 Apr 1;15(4):e090404. doi: 10.1136/bmjopen-2024-090404.

  PMID: 40169282 DERIVED

MeSH Terms

Conditions

Shock, Septic; Atrial Fibrillation

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases

Study Officials

• Vincent LABBE, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vincent LABBE, MD

CONTACT

01 56 01 69 37; vincent.labbe@aphp.fr

Armand Mekontso-Dessap

CONTACT

00 33 1 49 81 23 94 (23 89); armand.dessap@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2021
• First Posted: April 14, 2021
• Study Start: November 9, 2021
• Primary Completion: February 1, 2026
• Study Completion: March 1, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Locations

FR (1)