Albumin To Enhance Recovery After Acute Kidney Injury: A Multi-Centre, Randomized, Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 856
- 试验地点
- 16
- 主要终点
- Organ-support-free days (OSFD)
研究概览
简要总结
Study objectives:
To determine whether, in critically ill patients with Acute Kidney Injury requiring renal replacement therapy (AKI-RRT), randomization to receive intravenous hyperoncotic albumin 20-25% (100 mL X two doses) compared to control/placebo normal saline boluses (100 mL X two doses) given during RRT sessions, leads to:
- An increase in organ support-free days (primary outcome) at 28 days following randomization; and
- An increase in RRT-free days (principal secondary outcome) at 28 days following randomization.
详细描述
Background: Severe Acute Kidney Injury that necessitates renal replacement therapy (AKI-RRT) is a frequent complication of critical illness and portends severe outcomes: high morbidity, an approximately 50% risk of in-hospital death, and increased healthcare resource utilization. Although life-saving when needed, RRT itself may contribute to the poor outcomes associated with AKI-RRT. Since RRT treatments frequently cause hypotension, repeated episodes of kidney and other organ ischemia may occur during RRT. Hypotension during RRT is often triggered by fluid removal. At the same time, there is some evidence that more aggressive ultrafiltration could be beneficial in AKI-RRT.
Albumin is a protein that is the primary contributor to the colloid oncotic pressure maintaining the effective circulating volume (ECV) during RRT. Critically ill patients with AKI-RRT are nearly always hypoalbuminemic. Despite its high cost and limited evidence to support the practice, intravenous hyperoncotic albumin is commonly administered to patients with AKI-RRT in an effort to boost the colloid oncotic pressure and maintain the blood pressure while simultaneously facilitating fluid removal
Objective:
This proposed trial is intended to provide definitive evidence as to the efficacy of a frequently used and expensive intervention to promote hemodynamic stability and augment ultrafiltration during RRT in critically ill patients
Design: A randomized controlled trial with two parallel arms. Setting: The mixed medical-surgical intensive care units of five Canadian tertiary care hospitals with plans to expand to include other centres across Canada and internationally.
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
Blood Banks at participating sites prepare intravenous hyperoncotic albumin and normal saline (control) in identical infusion mini-bags. Opaque bags and intravenous tubing covers will be used to maintain blinding as much as possible.
The packaging for normal saline and 25% albumin will be identical (mini-bags) and be covered. The intravenous tubing will have an opaque sleeve to mask any colour discrepancy in the 2 product
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
- •Age ≥18 years old;
- •Admission to a critical care unit/intensive care unit (ICU) for > 24 hours;
- •Receiving vasoactive therapy AND/OR undergoing mechanical ventilation (including non-invasive mechanical ventilation (NIMV));
- •Immediate initiation of RRT for management of AKI is planned OR additional RRT sessions are imminently planned for patients who already received RRT during their ICU admission;
排除标准
- •Initiation of RRT for reasons other than AKI (e.g. drug intoxication, hypothermia) ;
- •Known pre-hospitalization end-stage kidney disease;
- •Kidney transplant within the past 365 days;
- •Presence or clinical suspicion of renal obstruction, rapidly progressive glomerulonephritis, vasculitis, thrombotic microangiopathy or acute interstitial nephritis;
- •Advanced cirrhosis (Child Pugh class C [score 10-15]), spontaneous bacterial peritonitis or hepatorenal syndrome;
- •Acute peritoneal dialysis used as the initial RRT modality;
- •Contraindications to albumin:
- •Admitted with traumatic brain injury
- •Increased intra-cranial pressure in those with intra-cranial pressure monitoring
- •Prior history of anaphylaxis to intravenous albumin
- •Contraindication or known objection to albumin/blood product transfusions
- •Already received 2 or more RRT sessions during ICU admission.
- •Limitations of medical therapy precluding RRT/mechanical ventilation/vasoactive medications or plan to transition to palliation
研究组 & 干预措施
20-25% Albumin fluid
100 mL 20-25% Albumin fluid at the initiation of continuous renal replacement therapy (CRRT), prolonged intermittent renal replacement therapy (PIRRT), or intermittent hemodialysis (IHD) and another 100 mL 20-25% Albumin fluid and halfway through RRT sessions in ICU.
干预措施: 20-25% Albumin fluid (100 mL) (Biological)
Normal Saline
100 mL at the initiation of CRRT, SLED or IHD and another 100 mL 0.9% Normal Saline halfway through RRT sessions in ICU.
干预措施: 0.9% Normal Saline (100 mL) (Other)
结局指标
主要结局
Organ-support-free days (OSFD)
时间窗: 28 days following randomization
Organ support-free days are defined as days that are both: 1) vasoactive therapy-free; AND 2) mechanical ventilation-free (including NIMV). For patients who die within 28 days following randomization, organ support-free days are counted as -1. An OSFD will be defined as the receipt of \< 2 hours of any vasoactive therapy provided by continuous infusion AND the receipt of \< 2 hours of either invasive or non-invasive mechanical ventilation, within a 24-hour period.
次要结局
- Number of participants with death in ICU(Through 28 days)
- Number of participants with RRT dependence at 90 days among surviving patients(Through 90 days.)
- Number of participants with death in ICU, at 28 days, and in-hospital(Through 90 days)
- Major adverse kidney outcomes, defined as death, RRT dependence, or sustained reduction in kidney function (defined as eGFR < 75% baseline eGFR) at 90 days.(Through 90 days)
- RRT-free days through day 28(Through day 28)
- Vasoactive therapy free days(Through day 28)
- Mechanical ventilation-free days(Though day 28.)
- eGFR will be evaluated in all patients alive at Day 90(At 90 days)
- Daily fluid balance after randomization up until ICU discharge or day 14, whichever comes first(Day 14 or ICU discharge)
- ICU free days(Through 28 days)
- Number of participants with all-cause mortality at 28 days(Through 28 days)
- Number of participants with all-cause mortality at 90 days(Through 90 days.)
- Hospitalization-free days(Through 90 days.)
- EuroQoL EQ-5D-5L which includes a descriptive system (scored from 5 (worst) to 25 (best)) and a visual analogue scale (scored from 0 (worst) to 100 (best)) at day 90.(At 90 days)
- Difference between ordered and achieved ultrafiltration for all intermittent HD / SLED treatments will be determined according to the medical record up until ICU discharge or day 14, whichever comes first(Day 14 or ICU discharge)
- Daily Sequential Organ Failure Assessment score (SOFA) score after enrollment up until ICU discharge or day 14, whichever comes first(Day 14 or ICU discharge)
- Number of participants with all-cause mortality at 365 days(Through 365 days)
- Number of participants with composite of death or RRT dependence at 90 days(Through 90 days.)
- Occurrence of RRT-associated hypotension (for every RRT session in ICU after randomization)(Through 14 days)
- Health Care Costs(Through 365 days.)
- Number of alive participants with RRT-dependence at 365 days(Through 365 days)
研究者
Edward Clark
Principal Investigator
Ottawa Hospital Research Institute