" ILOPROST for Treatment of Septic Shock With Persistent Microperfusion Defects ", a Double-blind, Randomized Controlled Trial:The I-MICRO Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Delta (Sequential Organ Failure Assessment (SOFA)) score between infusion onset and day 7. SOFA score assesses organ failure (respiratory, hemodynamics, liver, coagulation, neurological and kidney) in ICU patients.
研究概览
简要总结
Septic shock remains a major cause of death in critically ill patients. Alterations in microcirculation have long been proposed as a key pathophysiological factor of organ dysfunction and death in septic shock patients. Persistence of mottling, prolonged skin recoloration time and cyanosis of the extremities are the easily and frequently observed manifestations of these microcirculatory disorders. Ilomedin is a prostaglandin analog with a potent vasodilatory effect together with anti-thrombotic properties (inhibition of platelet aggregation) preferentially at the microcirculatory level. An increase in cardiac output with increased arterial oxygen delivery has been observed in clinical and preclinical studies with no episodes of hypotension. Improvement in mesenteric perfusion has moreover been observed in experimental sepsis using Ilomedin. Our group has furthermore reported that administration of Ilomedin in patients with refractory septic shock (peripheral hypoperfusion) resulted in a rapid and sustained improvement in peripheral perfusion. Altogether, Ilomedin may prevent or improve recovery of organ dysfunction in septic shock patients through recruitment of the microcirculation and, thereby, ultimately improve outcome.
详细描述
In the 32 participating centers: patients with septic shock and persistent peripheral hypoperfusion despite hemodynamic optimization (skin mottling and/or finger skin recoloration time > 3sec, and/or knee skin recoloration time > 4sec), after 6 to 24 hours of norepinephrine onset will be eligible for randomization.
Patients fulfilling the eligibility criteria will be included and randomized by the intensivist in two groups:
*Experimental group: The patient will receive treatment with intravenous Iloprost (blinded) therapy at a dose of 0.5 ng/kg/min with increments of 0.5 ng/kg/min every 30 minutes up to a maximum posology of 1.5ng/kg/min for 48h.
Placebo group: The patient will receive treatment with intravenous NaCl 0.9% (placebo-double blinded) therapy at a dose of 0.5ng/kg/min with increments of 0.5 ng/kg/min every 30 minutes according to body weight with a maximum posology of 1,5 ng/kg/min for 48h.
Primary outcome will be Delta Sequential Organ Failure Assessment (SOFA) score between infusion onset and day 7.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients over 18 years of age
- •Signed informed consent or inclusion under the emergency provisions of the law (Article L1122 -1-3 of the PHC / modified by Order n°2016-800 of June 16 2016 - art. 2).
- •Patients with septic shock defined by the third international definition:
- •suspected or proven infection,
- •and organ dysfunction defined by an acute change in total SOFA score >or=2
- •and persistent hypotension requiring vasopressor treatment to maintain mean arterial pressure > 65 mmHg despite standard of care hemodynamic optimization
- •and serum lactate level > 2 mmol/L despite standard of care hemodynamic optimization
- •and persistence of peripheral hypoperfusion (skin mottling and/or finger skin recoloration time > 3sec, and/or knee skin recoloration time > 4sec) despite standard of care hemodynamic optimization
- •Within 6 to 24 hours after norepinephrine onset
排除标准
- •Refusal to participate in the study
- •Pregnancy, breastfeeding
- •Hypersensitivity to Ilomedin or to any of the excipients.
- •Conditions where the hemorrhagic risk may be increased due to the effects of Ilomedin on platelets (i.e., evolving hemorrhage, trauma, intracranial hemorrhage, active gastric ulcer).
- •Platelet count < 10000 /mm3
- •unstable angina.
- •severe cardiac rhythm disorders since Norepinephrine onset
- •severe hypoxemia (PaO2/FiO2 <100)
- •myocardial infarction in the last 6 months
- •lack of Social Insurance
- •persons deprived of liberty
- •persons of a protective measure
研究组 & 干预措施
intravenous ILOPROST
a first dose of ILOPROST of 0.5ng/kg/ min with increments every 30 minutes up to a maximum of 1,5 ng/kg/min for 48h
干预措施: ILOPROST (Drug)
Intravenous Placebo
Treatment with intravenous NaCl 0.9% therapy with incremental infusion rate every 30 minutes for 48h
干预措施: NaCl (Drug)
结局指标
主要结局
Delta (Sequential Organ Failure Assessment (SOFA)) score between infusion onset and day 7. SOFA score assesses organ failure (respiratory, hemodynamics, liver, coagulation, neurological and kidney) in ICU patients.
时间窗: 7 days after randomisation
SOFA and Delta SOFA calculation will be performed by the Intensivist. Patients deceased before day 7 will be attributed a maximum SOFA score. SOFA score range from 0 (no organ failure) to a maximum of 24 (worst SOFA score).
次要结局
- Mean SOFA score during the first 7 days after randomization(7 days after randomization)
- Number of renal replacement therapy-free survival days in the 28 days post randomization -(Between randomization and day 28.)
- Number of vasopressor-free survival days in the 28 days post randomization(Between randomization and day 28.)
- Microcirculation(At the baseline, and between day 2 and day 7)
- Number of ventilation-free survival days in the 28 days post randomization(Between randomization and day 28.)
- Number of survival days outside ICU in the 28 days post randomization(Between ICU discharge and day 28)
- Molting score at day 1 after randomization.(At day 1 after randomization)
- mortality(At day 28)
- Conservation of plasma for future biological measurements(within 10 years after the end of the study.)