Early vs Late CRRT, a Propensity Matched Multicenter Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 50,000
- 试验地点
- 1
- 主要终点
- Mortality
研究概览
简要总结
Background: Severe acute kidney injury (AKI) among critically ill patients is sometimes treated with renal replacement therapy (RRT), and in Sweden continuous RRT (CRRT) is the dominant modality used in this population.
- The optimal timing of renal replacement therapy (RRT) initiation in critically ill patients with acute kidney injury (AKI) is unknown
- No consensus to guide clinical practice on this issue
- Lack of consistency regarding outcome measurements; should we look at morbidity or mortality?
- Wide variability in the timing of RRT initiation in the intensive care unit (ICU) population
Hypothesis: This is an important knowledge gap in the support of critically ill patients with AKI and we hypothesize that early initiation of RRT is beneficial.
Methods: The present study aims to test this hypothesis by using a large scale high resolution intensive care database, the Clinisoft repository. In this database, we have information on >60 000 patients from three different hospitals and five ICUs, during the years 2005 up until today. The repository will be crossmatched, using the unique Swedish national ID number, with hospital records; to gather information on preexisting illnesses, chronic medication and post-ICU outcomes. It is likely that over 5%, more than 3000 patients, have been treated with RRT. We will categorize these patients into "early" and "late" groups using both biomarker data and clinical data. Importantly, early and late RRT can be categorized using biomarkers, like urea and creatinine; using degree of fluid accumulation, by level of pH in blood and just by using hours-days after ICU admission. All possible definitions of early/late RRT initiation can be tested in this study.
Outcomes: Our primary outcome is 90 day mortality. Secondary outcomes include: mortality at 30, 60, 180 and 365 days. Two- and three year mortality.
Morbidity, measured as end-stage renal disease (ESRD) for 90-day survivors. ICU length of stay, hospital length of stay.
详细描述
Background
- Optimal timing of renal replacement therapy (RRT) initiation in critically ill patients with acute kidney injury (AKI) is unknown
- No consensus guides clinical practice on this issue
- Conflicting results from randomized controlled trials
- Lack of consistency regarding outcome; should we look at morbidity or mortality?
- Wide variability in the timing of RRT initiation in this population
- This is an important knowledge gap in the support of critically ill patients with AKI
Most previous studies have pointed to benefits of early RRT:
- The SOAP study (Payen 2008) enrolled> 3100 patients and 278 patients required RRT - in these patients, "early RRT" was defined as RRT initiation within two days of ICU admission while "late RRT" was defined as RRT initiation occurring thereafter. The early RRT group was significantly sicker, including higher SAPS II/SOFA scores, greater need for mechanical ventilation, and lower urine output compared to the late RRT group. Despite this (and without adjustment for these clinical differences at baseline), both ICU and hospital mortality along with ICU length of stay were significantly lower in the early RRT group.
- A secondary analysis of the FINNAKI (Vaara 2014) studied 239 critically ill patients with acute kidney injury treated with renal replacement therapy. The exposure was timing relative to evidence of developing ≥ 1 "conventional" indications, and three groups were defined. A) "Pre-emptive" - no conventional indication. B) "Classic - urgent" - renal replacement therapy started < 12 hr of indication. C) "Classic - delayed" - renal replacement therapy started ≥ 12 hr after indication. The analysis was stratified by group + propensity-matched analysis of "pre-emptive" to non-renal replacement therapy treated. 90-Day Mortality results were quite striking.
Pre-emptive renal replacement therapy vs. Classic renal replacement therapy 30% vs. 49%; OR 2.05; 95%, CI 1.0-4.1 Classic Urgent vs. Classic Delayed 39% vs. 68%; OR 3.85; 95% CI, 1.5-10.2 Pre-emptive vs. no renal replacement therapy (67% matched) 27% vs. 49% (diff 22.4%; 95% CI, 7.5-35.9) 3. Karvellas (2011) performed a meta-analysis comparing early vs late initiation of renal replacement therapy. 15 unique studies (2 randomised, 4 prospective cohort, 9 retrospective cohort) out of 1,494 citations. The overall methodological quality was low. Early, compared with late therapy, was associated with a significant improvement in 28-day mortality (odds ratio (OR) 0.45; 95% confidence interval (CI), 0.28 to 0.72). 4. Leite (2013) performed a study of 150 patients with AKIN stage 3. Mortality was lower in the early renal replacement therapy group (51.5 vs. 77.9%, P = 0.001). After achieving balance between the groups using a propensity score, there was a significant 30.5 (95% confidence interval [CI] 14.4 to 45.2%, P = 0.002) relative decrease of mortality in the early renal replacement therapy group. Moreover, patients on the early renal replacement therapy group had lower duration of mechanical ventilation, time on renal replacement therapy and a trend to lower intensive care unit (ICU) length of stay. 5. Shiao (2012) looked at 648 postoperative renal replacement therapy cases. Definitions were: early (EG, ≦1 day), intermediate (IG, 2-3 days), and late (LG, ≧4 days) groups. The in-hospital mortality rate censored at 180 day was defined as the endpoint. A U-shaped curve was found, indicating that intermediate start of renal replacement therapy was beneficial in this cohort. 6. The two RCTs; the AKIKI and ELAIN-studies (2016) from NEJM and JAMA report conflicting results. AKIKI showed no benefit with early initiation of renal replacement therapy but ELAIN did. Complicating matters were the fact that AKIKI dosing was unknown, and IHD was used in around 50% of those patients.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •*Critically ill patients admitted to intensive care units in Stockholm at: Karolinska University Hospital (Solna and Huddinge) and at Södersjukhuset.
- •*Patients over 18 years of age
排除标准
- •Patients <18 years
- •Patients with DNAR (do not attempt resuscitation)-orders
- •Patients dying within 12 hours of commencing renal replacement therapy.
结局指标
主要结局
Mortality
时间窗: 90-day mortality (mortality within 90 days of intensive care unit admission)
Date of death
次要结局
- ICU Length of Stay (LOS)(We will measure ICU LOS from ICU admission to ICU discharge, within 30 days of admission)
- Hospital LOS(We will measure Hospital LOS from ICU admission to hospital discharge, within 60 days of admission)
- End Stage Renal Disease(ESRD from 90 days after ICU discharge up to a maximum of 10 years)
- Mortality at other specified time-points(30-, 60-, 180-, 1-year, 2-year and 3-year mortality (mortality within those time points of intensive care unit admission))
研究者
Max Bell
MD, PhD, Associate Professor
Karolinska University Hospital