Terlipressin Versus Placebo for Septic Shock Refractory to High Doses Catecholamine Vasopressors: A Randomized-controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Achieve target blood pressure with low dose adrenergic agents
研究概览
简要总结
Norepinephrine was recommended as the first vasopressor for septic shock resuscitation.
For the patient who did not response to high dose norepinephrine, epinephrine was recommended.
Vasopressin was also recommended as an alternative vasopressor, in case patient did not response to norepinephrine and or epinephrine.
Terlipressin, a selective V1 receptor binding with long half life, was reported that it main action is to increase blood pressure via the different mechanism from norepinephrine and epinephrine.
To use terlipressin, combine with norepinephrine and or epinephrine among refractory septic shock, could decrease the usage dose of norepinephrine and epinephrine as well as lower the side effects of too high adrenergic stimuli.
详细描述
Norepinephrine was recommended as the first vasopressor for septic shock resuscitation.
For the patient who did not response to high dose norepinephrine, epinephrine was recommended.
Both norepinephrine and epinephrine action via the alpha adrenergic stimuli to increase vascular smooth muscle contraction, induced vasoconstriction and increase arterial blood pressure. It also action via beta adrenergic stimuli, to increase heart rate and myocardial contractility, then increase stroke volume and cardiac output.
Too much alpha and beta adrenergic stimulation, especially during received high dose norepinephrine and or epinephrine associated with vasoconstriction induce organs ischemia.
The most common organ ischemia included myocardial ischemia, bowel ischemia and limbs ischemia.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Performed a randomization table before enrollment. Prepare the study drug receiving or placebo receiving according to sequential number derived from the randomization table and keep it in a conceal envelop. Prepare study drug and placebo by a pharmacist or an investigation nurse, according to the randomization table number, and keep both study drug and placebo in the identical containment which labeled by a sequential number. Once a patient was enrolled and informed was signed, then study drug or placebo was start according to sequential number.
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
- •Septic shock according to Sepsis-3 definition
- •Evidence of adequate fluid
- •Received norepinephrine 0.2 mcg/kg/min or more
- •Received norepinephrine plus epinephrine (any dose)
- •Mean arterial lower than 65 mmHg or lactate > 2 mmol/liter
排除标准
- •Septic shock diagnosis > 48 hours before
- •Receive intravenous fluid < 30 mL/kg before enrollment
- •Do-not-resuscitation and terminally ill
- •Refractory to treatment malignancy
- •Chronic renal failure stage 5 with no plan for long term renal replacement therapy
- •Cirrhosis child C
- •Cardiogenic shock
- •Acute decompensated heart failure
- •Evidence of left ventricular ejection fraction (LVEF) < 35%
- •Acute coronary syndrome within 72 hours
- •Severe valvular heart disease
- •Documented life-threatening tachyarrhythmia before enrollment
- •Diagnosis of acute mesenteric ischemia before enrollment
- •Previous diagnosis of Raynaud's phenomenon
- •Known peripheral arterial disease
- •Refuse to sign the informed consent by patient or representative
研究组 & 干预措施
Terlipressin group
Terlipressin acetate 1 mg in 0.9% normal saline (NaCl) 50 mL (0.02 mg/mL) Initial dose 20 mcg/hr (1 mL/hr) titrate increase 1 mL/hr every 30 min to 100 mcg/hr (5 mg/hr) to keep mean arterial blood pressure (MAP) > 65 mmHg If MAP > 75 mmHg for > 30 min, decrease epinephrine and norepinephrine until < 0.15 mcg/kg/min, then decrease terlipressin until stop
干预措施: Terlipressin (Drug)
Placebo group
Placebo 0.9% NaCl 50 mL Initial dose 1 mL/hr titrate increase 1 mL/hr every 30 min to 5 mg/hr to keep mean arterial blood pressure (MAP) > 65 mmHg If MAP > 75 mmHg for > 30 min, decrease epinephrine and norepinephrine until < 0.15 mcg/kg/min, then decrease placebo until stop
干预措施: Placebo (Drug)
结局指标
主要结局
Achieve target blood pressure with low dose adrenergic agents
时间窗: 6 hours after initiate study drug
Achieve target mean arterial blood pressure 65 millimeter mercury or more with norepinephrine and/or epinephrine dose 0.2 mcg/kg/min or lower
次要结局
- 28 day mortality(28 days)
- Hospital mortality(90 days)
- ICU mortality(90 days)
- Mean arterial blood pressure(72 hours)