Systematic Adjunction of Vasopressine in Hyperkinetic Septic Shock Patients - A Multicentric RCT
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- SOFA score comparison between the two groups
研究概览
简要总结
Septic shock is a syndrome associated with severe infection and a mortality rate of approximately 45%. In line with current recommendations, norepinephrine is the first-line vasopressor used in patients with septic shock. In a previous study, norepinephrine doses above 1 µg/kg/min were associated with mortality rates over 90%. In the same study, doses above 0.3 µg/kg/min were associated with a mortality rate of 40%. An increased mortality compared to the general 40% mortality of septic shock appears to be associated with norepinephrine doses as low as 0.3 µg/kg/min.
Vasopressin stimulates V1 receptors, primarily located on vascular smooth muscle cells. When V1a receptors are stimulated, they induce vasoconstriction by activating protein kinase C via a Gq protein and various second messengers.
Its use is validated in refractory shock states by international guidelines as a second-line vasopressor. This indication was further reinforced in the 2021 update of the septic shock management recommendations.
The VASST study, a randomized controlled trial, assessed the effects of vasopressin versus norepinephrine in septic shock. It found no overall difference in mortality between the two groups. However, in less severe cases where norepinephrine doses were below 14 µg/min before randomization, vasopressin was associated with significantly lower mortality, suggesting potential benefits from early introduction of a second vasopressor.
The VANISH trial failed to confirm this hypothesis, possibly due to broad inclusion criteria and unclear protocol regarding the combined use of both agents. Our hypothesis is that (1) vasopressin is beneficial when used synergistically with norepinephrine; (2) due to its negative effect on cardiac output (as shown in previous studies), vasopressin should only be administered to patients in the hyperdynamic phase of septic shock.
The hypothesis is that the systematic addition of vasopressin to norepinephrine therapy in a hyperdynamic septic shock subpopulation would improve patient 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, Investigator, Outcomes Assessor)
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 or over
- •Patient who has consented to take part in the research or patient whose close relative has consented to take part in the research or, failing that, patient being included in an emergency situation
- •Patient in septic shock with adapted cardiac output
- •Patient in whom noradrenaline dosage has been greater than 0.3μg/kg/min for less than 12 hours
- •Patients benefiting from or affiliated to social security
排除标准
- •Patient with acute coronary syndrome
- •Patient with known history of acute coronary syndrome
- •Patient with suspected mesenteric ischemia
- •Patient with hyponatremia < 130mmol/L,
- •Known allergy to vasopressin or its excipients
- •Pregnant women
- •Patients under legal guardianship or curatorship
- •Patients under judicial protection.
研究组 & 干预措施
Vassopressine
干预措施: Vasopressin administration (Drug)
Placebo
干预措施: Sodium chloride administration (Drug)
结局指标
主要结局
SOFA score comparison between the two groups
时间窗: 48 hours after administration of experimental drug (H48)
Sepsis-related Organ Failure Assessment, 0 to 24 points (higher scores indicate more severe organ dysfunction)
次要结局
- SOFA score comparison between the two groups(120 hours after administration of experimental drug (H120))
- Mortality comparison between the two groups(28 days after administration of experimental drug (D28))
- Lactatemia decrease comparison between the two groups(Between administration of experimental drug (H0), 24 hours after (H24), and 48 hours after (H48))
- Noradrenaline use comparison between the two groups(5 days after administration of experimental drug (D5))
- Renal function comparison between the two groups(28 days after administration of experimental drug (D28))
- Respiratory function comparison between the two groups(28 days after administration of experimental drug (D28))
- Occurrence of myocardial ischemia comparison between the two groups(28 days after administration of experimental drug (D28))
- Occurrence of cardiogenic shock comparison between the two groups(28 days after administration of experimental drug (D28))
- Occurrence of mesenteric ischemia comparison between the two groups(28 days after administration of experimental drug (D28))
- Occurrence of digital ischemia comparison between the two groups(28 days after administration of experimental drug (D28))
- Occurrence of atrial fibrillation comparison between the two groups(28 days after administration of experimental drug (D28))
- Occurrence of a thromboembolic event comparison between the two groups(28 days after administration of experimental drug (D28))