REstrictive Versus LIberal Rate of Extracorporeal Volume Removal Evaluation in Acute Kidney Injury
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 99
- 试验地点
- 4
- 主要终点
- Delivered UFnet Rates.
研究概览
简要总结
Critically ill patients with acute kidney injury and fluid overload who are frequently treated by fluid removal during dialysis are at an increased risk of complications and death. Both slower and faster rates of fluid removal may cause injury to the vital organs. This proposed clinical trial will examine the feasibility of restrictive compared with a liberal rate of fluid removal in order to develop effective treatments for fluid overload and to improve the health of critically ill patients.
详细描述
"Net ultrafiltration (UFnet)," also known as net fluid removal during kidney replacement therapy, has been used in the treatment of fluid overload among critically ill patients with acute kidney injury (AKI) for more than seven decades. However, the optimal rate of fluid removal (i.e., UFnet rate) remains uncertain, complications such as hypotension and cardiac arrhythmias occur frequently, and more than 40% of patients die. Observational studies in critically ill patients receiving continuous kidney replacement therapy (CKRT) show that UFnet rate has a "J" shaped association with mortality with both slower and faster UFnet rates associated with increased risk of death compared with moderate UFnet rates.
The overall objective of this randomized trial is to establish the feasibility of maintaining patients in the restrictive UFnet rate strategy during treatment with CKRT. The investigator's central hypothesis is that a restrictive UFnet rate strategy embracing a "slow and steady" approach to fluid removal is associated with fewer complications, including cardiac arrhythmias, hypotension, and death, compared with a more liberal "sprint and pause" strategy among critically ill patients.
The trial is a prospective, two-center, unblinded, parallel-group, 2-arm, comparative effectiveness, stepped-wedge cluster-randomized trial among 112 critically ill patients with AKI treated with CKRT in 10 ICUs across two hospital systems. The trial will be conducted at 5 ICUs at University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania, as well as 5 ICUs at Mayo Clinic, Rochester, Minnesota. ICUs will be randomized 1:1 to either a restrictive or a liberal UFnet rate strategy. During the first six months, all ICUs will continue with a liberal UFnet rate strategy. Every two months thereafter or when 10 patients have been enrolled, whichever occurs first, one ICU will be randomized to deploy the restrictive UFnet rate strategy.
In the liberal group, the UFnet rate will be titrated between 2.0-5.0 mL/kg/h and maintained throughout fluid removal. In the restrictive group, the UFnet rate will be titrated between 0.5-1.5 mL/kg/h and maintained throughout fluid removal. The UFnet rates used in both strategies are used in current clinical practice.This feasibility trial will be used to support the rationale and design of a future multicenter phase III randomized trial to examine the effects of alternative UFnet rate strategies on patient-centered clinical outcomes.
Amendment changes- The "Delivered UFnet rates" outcome measure was amended based on a new calculation of effect size when we lowered the sample size from 144 patients to 112 patients in the trial.
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
- None
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 or older
- •Stage 3 acute kidney injury according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria
- •Started or intending to start CKRT for volume management
- •Attending intensivist or nephrologist intending to remove net fluid using CKRT for at least 48 hours
排除标准
- •Respiratory distress due to pulmonary edema or fluid overload in unintubated patients
- •Massive volume infusion (i.e., >200 mL/h for >6 hours of continuous infusion)
- •No intention to remove net fluid as determined by attending intensivist or nephrologist
- •Attending intensivist or nephrologist believes that the protocol will not be followed
- •Continuous net fluid removal for >48 hours prior to study enrollment
- •Patients on chronic outpatient hemodialysis
- •Patients with history of, or current admission for kidney transplantation
- •Patients on comfort measures only orders.
- •Moribund not expected to survive >24 hours
- •Confirmed pregnancy
- •Patients treated with extracorporeal membrane oxygenation, ventricular assist device, or intra-aortic balloon pump
- •Organ donors with neurological determination of death (i.e., brain dead donors)
- •Drug overdose requiring CKRT for drug clearance
- •Enrollment in a concurrent interventional clinical trial with direct impact on fluid balance (e.g., >500 mL study drug administration)
结局指标
主要结局
Delivered UFnet Rates.
时间窗: Until the end of continuous kidney replacement therapy or day 28, whichever occurs first.
A minimum separation of 0.53-0.57 mL/kg/h in mean delivered UFnet rates between the two intervention arms.
No. of Participants With Protocol Deviation.
时间窗: Until the end of continuous kidney replacement therapy or day 28, whichever occurs first.
Protocol deviation defined as delivered UFnet rate that lies \>0.5 mL/kg/h outside of the target UFnet rate range for greater than six consecutive hours.
Participant Recruitment/ICU/ 2 Months
时间窗: 24 months
An enrollment rate of 1 patient per ICU per time period.
次要结局
- Daily Fluid Balance (Average)(Average daily fluid balance from enrollment to ICU discharge or until day 28, whichever occurs first.)
- Cumulative Fluid Balance(Daily from enrollment to ICU discharge or until day 28, whichever occurs first.)
- Duration of Kidney Replacement Therapy(Daily from enrollment to hospital discharge or until day 28, whichever occurs first.)
- Duration of Mechanical Ventilation(Daily from study enrollment to ICU discharge or until day 28, whichever occurs first.)
- Organ Failure Free Days(Daily from study enrollment to ICU discharge or until day 28, whichever occurs first.)
- ICU Length of Stay(Daily from study enrollment to ICU discharge or day 28, whichever occurs first.)
- Hospital Length of Stay(Daily from study enrollment to hospital discharge or day 28.)
- Hospital Mortality(From study enrollment to hospital discharge or day 28, whichever occurs first.)
- Dependence on Kidney Replacement Therapy(From study enrollment until hospital discharge or day 28, whichever occurs first.)
研究者
Raghavan Murugan
Professor
University of Pittsburgh