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Supraventricular ArrhythmiaCAFSNCT04844801

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

A study of Supraventricular Arrhythmia and Septic Shock, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Supraventricular Arrhythmia, Septic Shock
Could I receive a placebo?
No, everyone receives an active treatment
How many people
240 participants
Where
1 siteFrance
Study dates
9 Nov 2021to Mar 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 12Show fewer
  • 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
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

France1 site, 1 recruiting
  • Service de Médecine Intensive Réanimation-Hôpital Tenon

    Paris, 75020

    François BAGATE, +33 1 45 17 85 14, francois.bagate@aphp.fr

    Armand Mekontso-Dessap, Professor, 0149812389, armand.dessap@aphp.fr

    Recruiting

Other trials in France

About this study

Official title: Comparison of Three Care Strategies in Cases of 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 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.

Read more

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.

Read the detailed 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.

Being tested
Risk control strategy, Heart-Rate control strategy:, Rhythm control strategy:
Keywords
New-onset supraventricular arrhythmia, Atrial fibrillation, Septic shock, Critically ill patient, Strategies, Antiarrhythmic drugs
Medical subject headings
Shock, Septic, Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Risk control strategyProcedure or surgery

    • 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.
  • Heart-Rate control strategy:Procedure or surgery

    • 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)
  • Rhythm control strategy:Procedure or surgery

    • 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
Study groups in NCT04844801
Study groupRoleWhat they receive
Risk control strategyActive comparatorMagnesium sulfate + control of the modifiable NOSVA risk factors
Receives: Procedure: Risk control strategy
Heart-Rate control strategyActive comparatorRisk-control + "low-dose" amiodarone
Receives: Procedure: Heart-Rate control strategy:
Rhythm control strategyActive comparatorRisk-control + "high-dose" amiodarone +/- electrical cardioversion
Receives: Procedure: Rhythm control strategy:

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 28 days

  2. 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.

    Measured: 28 days

Secondary outcomes (3)
  1. Rhythm efficacy at day-7 (or at discharge or death if before day-7)

    1. Number of patients with sinus rhythm
    2. Number of days alive with sinus rhythm
    3. Number of days alive with NOSVA and heart rate < 110 bpm
    4. Proportion of patients receiving therapeutic anticoagulation after randomisation

    Measured: up to 7 days

  2. Morbimortality

    1. Duration of septic shock and Length of stay in intensive care unit and in hospital at day-28
    2. Proportion of patients alive free from vasopressors at day-7 (or at discharge or death if before day-7)
    3. Arterial lactate clearance at day-3 defined as the percentage of arterial lactate decrease between lactate at randomisation (day-1) and at day-3.
    4. Proportion of patients alive free from organ dysfunction at day-7 (or at discharge or death if before day-7)
    5. All-cause deaths at day-28.

    Measured: Day 28

  3. Tolerance at day-7 and day-28

    1. Proportion of patients with at least one arterial thrombotic event including ischemic stroke and non-cerebrovascular arterial thrombotic event
    2. Proportion of patients with at least one major bleeding event according to the International Society of Thrombosis and Haemostasis definition at Day-28;
    3. Proportion of patients with at least one serious adverse event related to amiodarone or to magnesium sulfate; and proportion of each type of event
    4. Proportion of patients presenting at least one serious adverse event associated with electrical cardioversion (for patients receiving electrical cardioversion).

    Measured: Day 7 and day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2021
  2. Study start9 Nov 2021
  3. Primary completionFeb 2026 (estimated)
  4. Study completionMar 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
240 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04844801
Sponsor's protocol ID
APHP190070
Acronym
CAFS
Status last verified
Jan 2026
First submitted
26 Feb 2021
Last updated
7 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 40169282

Questions about this trial

What is this clinical trial studying?

A study of Supraventricular Arrhythmia and Septic Shock, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 7 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Vincent LABBE, MD (01 56 01 69 37, vincent.labbe@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

all-cause mortality (a hierarchical criterion) (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04844801, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2026.

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