Angiotensin II for Septic Shock Treatment: Effects On Macro- and Microcirculation A Randomized, Controlled Pilot Trial (ANGSTROM Trial)
试验速览
- 阶段
- 3 期
- 状态
- 暂停
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Mean flow index
研究概览
简要总结
This study aims to investigate the effect of angiotensin II on microcirculation and peripheral perfusion in patients with septic shock.
详细描述
Shock is a syndrome characterized by acute circulatory failure resulting in impaired peripheral tissue perfusion. Distributive shock is the most common type of shock and is usually caused by severe sepsis. Distributive shock is characterized by profound vasodilatation leading to decreased arterial blood pressure and impaired organ perfusion despite high cardiac output.
The use of vasopressors is an essential management line for distributive sock. Two groups of vasopressors are usually used for management of shock: catecholamines and vasopressin-like peptides. There is a continuous need for other vasopressors because:
1- Available vasopressors have narrow therapeutic window. 2- Patients with severe hypotension refractory to the currently available classes usually die.
A third system is usually engaged in the physiology of shock which is Renin-Angiotensin-aldosterone system. Angiotensin II is a natural hormone which is a potent vasopressor; moreover, angiotensin II stimulates the production of both antidiuretic hormone and adrenocorticotropin hormone.
In a pilot study, angiotensin II was reported as an effective rescue vasopressor in septic shock patients on multiple vasopressors. Angiotensin II improved mean arterial pressure and helped in reduction of the doses of catecholamines. In a recent large randomized controlled trial, angiotensin II improved blood pressure in catecholamine-resistant distributive shock patients.
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)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Septic shock patients.
- •Aged above 18 years.
- •With cardiac index > 2.4 L/min/BSA 1.73 m
- •On high dose vasopressors (defined as norepinephrine infusion above 0.1 mcg/Kg/min)
排除标准
- •Acute coronary syndrome.
- •Impaired cardiac contractility
- •Bronchospasm.
- •Major burns
- •Liver failure.
- •Active bleeding.
研究组 & 干预措施
Angiotensin group
Patients will receive Angiotensin II at a starting dose of 20 ng/Kg/min. During the first 30 minutes after randomization, the angiotensin II infusion will be titrated to achieve a mean arterial pressure of 65-75 mmHg while the norepinephrine infusion will be withdrawn and stopped. Following a stabilization of 60 minutes, the angiotensin II infusion is titrated to achieve a mean arterial pressure of 85-95 mmHg. Following a 30 minutes wash-in period and a 60 minutes stabilization period, a third set of measurements will be taken. Then, the angiotensin II infusion will be withdrawn in small steps and replaced by a norepinephrine infusion which will then be titrated to achieve a mean arterial pressure of 65-75 mmHg. Then, the final set of measurements will be taken.
干预措施: Angiotensin II (Drug)
Angiotensin group
Patients will receive Angiotensin II at a starting dose of 20 ng/Kg/min. During the first 30 minutes after randomization, the angiotensin II infusion will be titrated to achieve a mean arterial pressure of 65-75 mmHg while the norepinephrine infusion will be withdrawn and stopped. Following a stabilization of 60 minutes, the angiotensin II infusion is titrated to achieve a mean arterial pressure of 85-95 mmHg. Following a 30 minutes wash-in period and a 60 minutes stabilization period, a third set of measurements will be taken. Then, the angiotensin II infusion will be withdrawn in small steps and replaced by a norepinephrine infusion which will then be titrated to achieve a mean arterial pressure of 65-75 mmHg. Then, the final set of measurements will be taken.
干预措施: Norepinephrine (Drug)
Normal saline group
Patients will receive normal saline infusion in addition to norepinephrine infusion. The same mean arterial pressure levels (65-75 mmHg > 85-95 mmHg > 65-75 mmHg) will be achieved by titration of the norepinephrine infusion. Identical wash-in and stabilization periods will be kept as in the study group. Measurements will be taken at the same time points as in the study group. The maximum dose of norepinephrine applied will be 0.7 mcg/kg/min.
干预措施: Normal saline (Drug)
Normal saline group
Patients will receive normal saline infusion in addition to norepinephrine infusion. The same mean arterial pressure levels (65-75 mmHg > 85-95 mmHg > 65-75 mmHg) will be achieved by titration of the norepinephrine infusion. Identical wash-in and stabilization periods will be kept as in the study group. Measurements will be taken at the same time points as in the study group. The maximum dose of norepinephrine applied will be 0.7 mcg/kg/min.
干预措施: Norepinephrine (Drug)
结局指标
主要结局
Mean flow index
时间窗: 6 Hours
Mean flow index measured by Side stream dark field imaging optical probe (Microscan; MicroVision Medical, Amsterdam, Netherlands). Briefly, after gentle cleansing of the tongue by isotonic-saline-drenched gauze, avoiding pressure artifacts, 5 steady images of at least 20 seconds each will be obtained and stored under a random number. Offline blind analysis of each video will be done using a dedicated software (Automated Vascular Analysis 3.0; Academic Medical Center, University of Amsterdam, The Netherlands). The microvascular flow index (MFI) will be used to quantify microvascular blood flow. In this score, flow is characterized as absent (0), intermittent (1), sluggish (2), or normal (3), for each patient the values from 5 videos will be averaged. Since our investigation will be focused on small vessels, calculations will be separately performed for vessels with a diameter less than 20 ųm.
次要结局
- Heart rate(6 hours)
- Serum Sodium(24 hours)
- Serum potassium(24 hours)
- total fluid intake(24 hours)
- Perfused vessel density(6 Hours)
- Serum lactate(6 hours)
- Proportion of perfused vessels(6 Hours)
- systolic blood pressure(6 hours)
- Diastolic blood pressure(6 hours)
- Urine output(6 hours)
- Serum Creatinine(24 hours)
- Cardiac output(6 hours)
- systemic vascular resistance(6 hours)
- Norepinephrine requirements(6 hours)
- perfusion index(6 hours)
研究者
Ahmed Hasanin
Assistant professor
Cairo University