Pilot Phase II Study: Hemodynamic Tolerance and Anti-inflammatory Effects of Esmolol During the Treatment of Septic Shock
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Comparison of hemodynamic parameters between 3 groups
研究概览
简要总结
The purpose of this study is :
- to evaluate the hemodynamic tolerance of esmolol titrated to obtain a lowering of heart rate of 10% or 20%.
详细描述
During septic shock, the consequences of treatment by a β1-blocker on inflammation and cardiovascular variability are unknown. The use of esmolol should have positive effects on inflammation and hemodynamic tolerance. These effects are probably dose-dependent.
The study will enroll adult patients hospitalized in ICU, for severe septic shock requiring treatment by a vasopressor.
A total of 45 patients will be included. Among these 45 patients, 15 patients will be randomized in the control group. 30 patients will be randomized to Esmolol with the objective to decrease heart rate by 10% (Group G10, n=15) or 20% (Group G20, n=15). Esmolol will be administered for 24 hours.
This multicenter study will be performed in 3 investigation sites.
The following parameters will be evaluated at different moments during the 28 days follow up of each patient, mainly:
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
- •Patient aged ≥ 18 years;
- •Patient with septic shock;
- •Patient with arterial catheter, central venous catheter with PVC and PiCCO;
- •Consent signed by patient. In the absence of a consent signed by patient himself, a consent by a family member will be sought. As soon as possible, the patient will be informed and asked to sign a consent for continuing of study;
- •Hemodynamic stability of patient during 1 hour without change in norepinephrine dosage;
- •Treatment with noradrenaline for less than 48 hours.
排除标准
- •Need of noradrenaline > 3 mg/h;
- •Treatment with dobutamine;
- •Personal history of severe asthma;
- •Personal history of severe chronic obstructive pulmonary disease;
- •Personal history of pulmonary hypertension;
- •Personal history of second degree or third degree atrioventricular block without pacemaker;
- •Personal history of sinoatrial block without pacemaker;
- •Chronic heart failure with ejection fraction < 40%;
- •Severe atrioventricular nodal bradycardia (heart rate < 70 bpm);
- •Mean arterial pressure < 65 mm Hg;
- •Hypersensitivity to esmolol;
- •Prinzmetal angina;
- •Pheochromocytoma without treatment;
- •Pregnancy woman;
- •Breastfeeding woman;
- •Peripheral arterial disease;
- •Patient with pacemaker;
- •Chronic treatment with a beta blocker;
- •Concomitant treatment with bepridil, diltiazem, verapamil, amiodarone, propafenone, Class Ia antiarrythmics (hydroquinidine, disopyramide) or baclofen;
- •Patient < 18 years;
- •Patient under the care of a guardian;
- •Therapeutic futility;
- •Lack of medical insurance.
研究组 & 干预措施
Group 10 (G10)
Esmolol titrated in order to reduce heart rate by 10% as compared to baseline heart rate
干预措施: Esmolol administration (Drug)
Group 20 (G20)
Esmolol titrated in order to reduce heart rate by 20% as compared to baseline heart rate
干预措施: Esmolol administration (Drug)
结局指标
主要结局
Comparison of hemodynamic parameters between 3 groups
时间窗: 24 hours
3 groups: GC, G10 and G20. The hemodynamic tolerance will be considered as satisfactory if the variation of MAP and cardiac output induced by esmolol does not exceed 15% of baseline (H0).
Immunomodulatory effect
时间窗: 24 hours
Immunomodulatory effect of esmolol will be evaluated notably by the ratio of IL6 / IL10. The decrease of this ratio in comparison with the value at baseline (H0) will be considered as an indicator of esmolol efficacy as immunomodulator.
次要结局
- Comparison of mortality in the 3 groups(28 days)
- Comparison of number and severity of organ failures, between the 3 groups(28 days)
- Comparison of autonomic nervous system activity between the 3 groups(24 hours)
- Comparison in the 3 groups of the correlations between the biomarkers and the hemodynamic data(24 hours)