Clinical trial NCT03175328: CRRT Timing in Sepsis-associated AKI in ICU
Official title: The Timing of Continuous Renal Replacement Therapy Initiation in Sepsis-associated Acute Kidney Injury in the Intensive Care Unit
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Sepsis-Associated Organ Dysfunction
RTT
Lead sponsor: Second Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
First posted: 2017-06-05
Enrollment: 460
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Sepsis continues to be a major global cause of both mortality and morbidity. Furthermore, the development of acute kidney injury (AKI) in sepsis increases the risk of unfavorable outcomes. Besides source control, fluid resuscitation and the use of antibiotics, application of extracorporeal renal replacement therapies (RRT) is the predominant treatment for sepsis-associated AKI (SAKI). However, the timing of initiation of RRT remains controversial. It is reported that a correlation was observed between the concentrations of circulating inflammatory cytokines and mortality in patients with septic shock. Therefore, it is hypothesis that adequate removal of inflammatory mediators from the circulation may provide a potential therapy for this devastating condition. Indeed, data from meta-analyses, observational studies and randomized controlled trial (RCT) suggests that initiating RRT in critical ill patients (including patients with sepsis and non-sepsis) at early stage may be beneficial. But in some studies, initiating RRT at early stage do not shown to improve survival compared with initiating RRT at late stage. At present, large-scale prospective RCT about the timing for initiating RRT in SAKI was still lack.The decision when to start RRT is not merely academic but may impact on outcomes. Therefore, in our study, 460 patients with SAKI at KDIGO 2 from multicenter in China will be recruited. And then the patients will be divided into early group and delayed group randomly. In the early group, continuous RRT (CRRT) was started immediately after randomization. In the delay group, CRRT was initiated if at least one of the following criteria was met: KDIGO 3, severe hyperkalemia, pulmonary edema, blood urea nitrogen level higher than 112 mg per deciliter after randomization. Overall survival at day 90 will be observed in order to understand whether different CRRT strategy would affect the outcomes of SAKI. This clinical study will be a large-scale, multi center, prospective, randomized trial about SAKI. It will help clinician choose appropriate timing to initiate CRRT and improve outcomes of SAKI.

Detailed description: In our study, 460 patients with SAKI at KDIGO 2 from multicenter in China will be recruited. And then the patients will be divided into early group and delayed group randomly. In the early group, CRRT was started immediately after randomization. In the delay group, CRRT was initiated if at least one of the following criteria was met: KDIGO 3, severe hyperkalemia, pulmonary edema, blood urea nitrogen level higher than 112 mg per deciliter after randomization. Overall survival at day 90 will be observed in order to understand whether different CRRT strategy would affect the outcomes of SAKI.

Eligibility criteria: Inclusion criteria

1. Age between 18 and 90 years.
2. Patients admitted into ICU with Sepsis (sepsis-3) compatible with the diagnosis of AKI at stage 2 of KDIGO classification.
3. Informed consent provided by the patient or person with decisional responsibility.

Exclusion criteria

1. Presence of one of the emergent CRRT conditions before randomization:

1. Hyperkalemia \> 6.0 mmol/L or \> 5.5 mmol/L persisting despite medical treatment.
2. Acute pulmonary edema due to fluid overload responsible for severe hypoxemia requiring oxygen flow rate \> 5 L/min to maintain a percutaneous oxygen saturation (SpO2) \> 95% or a fraction of inspiration oxygen (FiO2) \> 50% in patients already on invasive or non-invasive mechanical ventilation and despite diuretic therapy.
3. Blood urea nitrogen (BUN) \> 112 mg/dl (40 mmol/L). 2. Pre-existing severe chronic renal failure \[estimated glomerular filtration rate (eGFR) \< 30 ml/min\].

3. Previous renal replacement therapy. 4. Prior kidney t

Primary outcomes:
measure: overall mortality
timeFrame: 90 days
Secondary outcomes:
measure: recovery rate of renal function
timeFrame: 90 days
measure: organ dysfunction
timeFrame: 90 days
measure: length of ICU stay and in-hospital stay
timeFrame: 90 days
measure: the percentage of receipt of CRRT at least once in the delayed group
timeFrame: 90 days
measure: the number of days alive without CRRT, mechanical ventilation and vasopressor
timeFrame: 90 days
measure: difference of the Sequential Organ Failure Assessment score
timeFrame: 28 days
measure: the rate of complications potentially related to CRRT
timeFrame: 90 days
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: the Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: the Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: Second Affiliated Hospital of Guangzhou Medical University
name: Xu-ming Xiong, PHD
role: STUDY_DIRECTOR
References:
citation: Chen WY, Cai LH, Zhang ZH, Tao LL, Wen YC, Li ZB, Li L, Ling Y, Li JW, Xing R, Liu XY, Lin ZD, Deng ZT, Wang SH, Lin QH, Zhou DR, He ZJ, Xiong XM. The timing of continuous renal replacement therapy initiation in sepsis-associated acute kidney injury in the intensive care unit: the CRTSAKI Study (Continuous RRT Timing in Sepsis-associated AKI in ICU): study protocol for a multicentre, randomised controlled trial. BMJ Open. 2021 Feb 19;11(2):e040718. doi: 10.1136/bmjopen-2020-040718.