Comparison of Three Care Strategies in Cases of New-onset Supraventricular Arrhythmia During Septic Shock : a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 240
- 试验地点
- 2
- 主要终点
- all-cause mortality (a hierarchical criterion)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
- •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
研究组 & 干预措施
Risk control strategy
Magnesium sulfate + control of the modifiable NOSVA risk factors
干预措施: Risk control strategy (Procedure)
Heart-Rate control strategy
Risk-control + "low-dose" amiodarone
干预措施: Heart-Rate control strategy: (Procedure)
Rhythm control strategy
Risk-control + "high-dose" amiodarone +/- electrical cardioversion
干预措施: Rhythm control strategy: (Procedure)
结局指标
主要结局
all-cause mortality (a hierarchical criterion)
时间窗: 28 days
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.
the duration of septic shock according to the Finkelstein-Schoenfeld method (a hierarchical criterion).
时间窗: 28 days
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.
次要结局
- 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)