Five Percent Albumin Versus Normal Saline as Fluid Resuscitation Strategies for the Management of Early Suspected Septic Shock
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 6
- 主要终点
- Comparison of thrombin generation and protein C and APC levels
研究概览
简要总结
Severe infection in the intensive care unit is common accounting for about 10% of admissions and has a death rate of approximately 40-50%. It is almost always associated with significant reductions in blood pressure. Administration of fluid often in large volumes is essential to normalize blood pressure and prevent failure of organs and death. Two common classes of fluid solutions are crystalloid fluids (salt based, normal saline) and colloid fluids (protein based, albumin). Due to its properties, the albumin fluid may remain in the vascular space better than the normal saline solution. Hence, there may be faster attainment of normal blood pressure as well as a reduction in failed organs and death. Preliminary clinical trial data suggests a potential for benefit with albumin in this setting but these findings require confirmation in a large clinical trial.
There are few data to explain how albumin may exert its protective effects and lead to better outcomes for patients with severe infections. We will conduct a clinical study that will examine potential biological mechanisms for albumin's protective effects in 50 patients across 6 Canadian academic hospitals. We will also examine our ability to successfully recruit patients into this trial.
This study will provide information that will help to understand the biological mechanisms of albumin in severe infection. The information gained will guide the investigative team for future fluid related mechanistic questions. The study will also provide essential information that will aid in the design and conduct of the future large clinical trial that will examine death as its primary outcome.
详细描述
Background: Severe sepsis and septic shock are the most common causes of mortality among critically ill patients and account for approximately 10% of admissions to the intensive care unit (ICU) and 3% of all admissions to hospital. Despite decades of therapeutic investigation, mortality of septic shock has remained at approximately 40-50%. Fluid resuscitation is an integral component of early treatment, as several liters of fluid may be administered in the first hours of septic shock in an attempt to re-establish hemodynamic stability. The two main classes of fluid expand the plasma volume include crystalloids and colloids.
In Canada, the main crystalloid fluids used for resuscitation are normal saline and ringers lactate; the main colloid fluids used for resuscitation are hydroxyethyl starches (HES) and albumin. Until recently, no randomized controlled (RCT) or systematic review had confirmed benefit or harm with either colloidal or crystalloid fluids in this patient population. An RCT published in 2008 demonstrated that 10% pentastarch (HES fluid) causes acute renal failure defined by the requirement for renal replacement therapy. In contrast, a subgroup analysis from a RCT of severe sepsis suggests that 4% albumin fluid may reduce death. However, these hypothesis-generating findings require confirmation in the context of a large RCT.
There are limited observational mechanistic studies designed to understand the potential biological mechanisms for albumin's potential protective effects in sepsis. Moreover, mechanistic data in the clinical trial setting are lacking. The PRECISE pilot RCT (Five Percent Albumin versus Normal Saline as Fluid Resuscitation Strategies for the Management of Early Suspected Septic Shock) will help to understand the biological mechanisms of albumin in early septic shock and explore feasibility issues in preparation for a large RCT.
Study Hypotheses: We hypothesize that resuscitation with 5% albumin as compared to normal saline in early septic shock may exert some of its protective effects through the following biological mechanisms: 1) Limiting thrombin generation, 2) Supporting endogenous protein C and activated protein C (APC) generation, 3) Limiting the production of systemic pro-inflammatory cytokines and chemokines and supporting the production of cytokines and chemokines with anti-inflammatory potential, and 4) Reducing the ability of septic plasma to generate Neutrophil Extracellular Traps (NETs).
Study Design/Setting: A multi-centre randomized controlled trial conducted in 6 Canadian academic centres.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligible patients will meet the following 2 inclusion criteria.
- •Refractory Hypotension: The patient has received at least 1 litre of normal saline or ringers lactate crystalloid fluid for hypotension (defined as a systolic blood pressure less than 90 mm Hg, or a systolic blood pressure more than 40 mm Hg below baseline, or a mean arterial blood pressure less than 65 mm Hg) within 8 hours of the first hypotensive event and has refractory hypotension defined by: a) Presence of hypotension OR b) Initiation of a vasopressor agent(s).
- •Two or more criteria for the systemic inflammatory response syndrome (SIRS): i) heart rate greater than 90 beats per minute; ii) respiratory rate greater than 20 breathes per minute, or a PaC02 less than 32 mm Hg, or mechanically ventilated; iii) temperature greater than 38 or less than 36 degrees Celsius; iv) or a white blood cell count greater than 12,000 x 109/L or less than 4,000 x 109/L, or more than 10% bands on the differential.
排除标准
- •Clinically apparent other forms of shock including cardiogenic, obstructive (massive pulmonary embolism, cardiac tamponade, tension pneumothorax) or hemorrhagic shock
- •Previous admission to ICU with severe sepsis or septic shock during the index hospitalization
- •More than 250 mls of colloid fluid (Pentaspan, Voluven, Hextend, or albumin) from the first episode of hypotension
- •A known previous severe reaction to albumin
- •Known cirrhosis
- •Traumatic brain injury
- •Religious objection to albumin use
- •Less than 18 years of age
- •Family or patient not committed to aggressive care
- •Currently enrolled in another related interventional study.
研究组 & 干预措施
1
5% albumin
干预措施: 5% albumin (Drug)
2
Normal saline
干预措施: Normal Saline (Drug)
结局指标
主要结局
Comparison of thrombin generation and protein C and APC levels
时间窗: Thrombin generation at 72 hours and protein C and APC levels at 7 days after randomization
次要结局
- Comparison of blood and urine pro and anti-inflammatory cytokine and chemokine levels.Clinical outcomes include mortality, length of stay,organ failure, and organ support measures.(Inflammatory markers measured first 7 days of care. Mortality in ICU/hospital/30 days. Length of stay ICU/hospital. Organ failure first 7 days of care.)