Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion: a Randomized Controlled Multi-center Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 136
- 试验地点
- 21
- 主要终点
- Sequential Organ Failure Assessment (SOFA) score evolution
研究概览
简要总结
Sepsis induces both a systolic and diastolic cardiac dysfunction. The prevalence of this septic cardiomyopathy ranges between 30 and 60% according to the timing of assessment and definition used. Although the prognostic role of septic cardiomyopathy remains debated, sepsis-induced left ventricular (LV) systolic dysfunction may be severe and associated with tissue hypoperfusion, while it appears to fully recover in survivors. Accordingly, optimization of therapeutic management of septic cardiomyopathy may contribute to improve tissue hypoperfusion in increasing oxygen delivery, and to reduce related organ dysfunctions in septic shock patients.
Echocardiography is currently the recommended first-line modality to assess patients with acute circulatory failure.
Current Surviving Sepsis Campaign strongly recommends Norepinephrine as the first-choice vasopressor in fluid-filled patients with septic shock. In contrast, the use of Dobutamine is only suggested (weak recommendation, low quality of evidence) in patients with persistent tissue hypoperfusion despite adequate fluid resuscitation and vasopressor support. Levosimendan, an alternative inodilator, has failed preventing acute organ dysfunction in septic patients and has induced more supraventricular tachyarrhythmias than in the control group. Data supporting Dobutamine in this setting are scarce and primarily physiologic and based on monitored effects of this drug on hemodynamics and indices of tissue perfusion.
No randomized controlled trials have yet compared the effects of Dobutamine versus placebo on clinical outcomes. In open-labelled, small sample trials, the ability of septic patients to increase their oxygen delivery during Dobutamine administration appears to be associated with lower mortality.
The tested hypothesis in the ADAPT trial is that Dobutamine will reduce tissue hypoperfusion and associated organ dysfunctions in patients with septic shock and associated septic cardiomyopathy. In doing so, it may participate in improving clinical outcomes.
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
- Triple (Participant, Care Provider, Investigator)
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 hospitalized in ICU
- •> Septic shock (Sepsis-3 definition):
- •Clinically suspected or documented acute infection
- •Responsible for organ dysfunction(s): change in SOFA ≥ 2 points
- •With persisting hypotension (systolic and/or mean arterial pressure < 90 / < 65 mmHg) despite adequate fluid resuscitation (≥ 30 mL/kg, unless presence of pulmonary venous congestion)
- •Requiring vasopressor support (Norepinephrine) to maintain steady mean arterial pressure ≥ 65 mmHg
- •And lactate > 2 mmol/L
- •Septic cardiomyopathy: echocardiographically measured LV ejection fraction (EF) ≤ 40% and LV outflow tract velocity-time integral < 14 cm
- •Informed consent
排除标准
- •Pregnancy or breast feeding
- •Hypersensitivity to Dobutamine, 5% Dextrose, or to the excipients
- •Ventricular rate > 130 bpm (sinus rhythm or not)
- •Severe ventricular arrhythmia
- •Obstructive cardiomyopathy with pressure gradient at rest ≥ 50 mmHg unrelated to uncorrected hypovolemia
- •Severe aortic stenosis: mean gradient > 40 mmHg, peak aortic jet velocity > 4 m/s, aortic valve area < 1 cm² (aortic valve area index < 0.6 cm²/m²)
- •Acute coronary syndrome
- •Decision to limit care or moribund status (life expectancy < 24 h)
- •Absence of affiliation to Social Security
- •Subjects under juridical protection.
研究组 & 干预措施
Control
Placebo will initially be started at a dose of 2.5 µg/kg/min and subsequently titrated using incremental steps (predefined durations) of 2.5 µg/kg/min, up to a maximal dose of 10 µg/kg/min
干预措施: Placebos (Drug)
Experimental
Dobutamine will initially be started at a dose of 2.5 µg/kg/min and subsequently titrated using incremental steps (predefined durations) of 2.5 µg/kg/min, up to a maximal dose of 10 µg/kg/min
干预措施: Dobutamine (Drug)
结局指标
主要结局
Sequential Organ Failure Assessment (SOFA) score evolution
时间窗: Day 0 to Day 3
Evolution of a modified Sequential (Sepsis-Related) Organ Failure Assessment (SOFA) score (no gradation of the neurologic system) between baseline (before randomization) and Day 1, Day 2 and Day 3 after randomization. Min value =0. Max value =20 . The highest score means the worst situation
次要结局
- Circulating lactate level measurement(Hour 0, Hour 6, Day 1, Day 2 and Day 3)
- Central venous oxygen saturation (ScvO2) measurement(Hour 0, Hour 6, Day 1, Day 2 and Day 3)
- Open-labelled Dobutamine dayly maximal dose used as rescue therapy(through study completion, an average 90 days)
- Open-labelled Dobutamine duration used as rescue therapy(through study completion, an average of 90 days)
- Vasopressor support duration(through study completion, an average of 90 days)
- Vasopressor support dayly maximal dose(through study completion, an average of 90 days)
- Invasive mechanical ventilation duration(through study completion, an average of 90 days)
- Renal replacement therapy number(through study completion, an average of 90 days)
- Renal replacement therapy duration(through study completion, an average of 90 days)
- Arterial pressure measurement(Hour 0, Hour 6, Day 1, Day 2 and Day 3)
- heart rate measurement(Hour 0, Hour 6, Day 1, Day 2 and Day 3)
- Central venous pressure measurement(Hour 0, Hour 6, Day 1, Day 2 and Day 3)
- Cardiac index measurement(Hour 0, Hour 6, Day 1, Day 2 and Day 3)
- Stroke volume measurement(Hour 0, Hour 6, Day 1, Day 2 and Day 3)
- Hypotension measurement(Hour 0, Hour 6, Day 1, Day 2 and Day 3)
- Supraventricular arrhythmias measurement(through study completion, an average of 90 days)
- Ventricular arrhythmias measurement(through study completion, an average of 90 days)
- Occurence of Acute coronary syndrome(through study completion, an average of 90 days)
- Occurence of Stroke(through study completion, an average of 90 days)
- Mortality(Day 90)
- Mortality causes(Day 90)
- Organ function free supports(Day 90)
- Number of days in ICU and hospital(Day 90)
- echocardiographic assessment of left ventricular systolic function(Day 0 and Day 1)
- Leucocyte subsets level(Hour 6)
- Cytokines level(Hour 6)
- LV global longitudinal strain measurement(Hour 6, Day 1, Day 2 AND Day 3)
- RV free wall strain measurement(Hour 6, Day 1, Day 2 AND Day 3)
- LV volume measurement(Hour 6, Day 1, Day 2 AND Day 3)
- LV ejection fraction measurement(Hour 6, Day 1, Day 2 AND Day 3)
- RV volume measurement(Hour 6, Day 1, Day 2 AND Day 3)
- RV ejection fraction measurement(Hour 6, Day 1, Day 2 AND Day 3)
- Transpulmonary thermodilution measurement(Hour 6, Day 1, Day 2 AND Day 3)