CRRT Timing in Sepsis-associated AKI in ICU (CRTSAKI)

The Timing of Continuous Renal Replacement Therapy Initiation in Sepsis-associated Acute Kidney Injury in the Intensive Care Unit

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.

Study Overview

• Status: Recruiting
• Conditions: RTT; Sepsis-Associated Organ Dysfunction
• Intervention / Treatment: Procedure: continuous renal replacement therapies

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.

• Study Type: Interventional
• Enrollment (Anticipated): 460
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xu-ming Xiong; Phone Number: +86 20 34152225; Email: xiongxuming9@126.com
• Study Contact Backup: Name: Wei-yan Chen, MD; Phone Number: +86 20 34153246; Email: sam11124@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510260
      • Recruiting
      • The second Affiliated Hospital of Guangzhou Medical University
      • Contact: Xu-ming Xiong, PHD; Phone Number: +86 18926298697; Email: xiongxuming9@126.com
      • Contact: Wei-yan Chen, MD; Phone Number: +86 13751845652; Email: sam11124@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: early group; In the early group, continuous renal replacement therapies was started within 8 hours after randomization.	Procedure: continuous renal replacement therapies; The choice of the method of continuous renal replacement therapy (device setting and anticoagulation method) is left to the discretion of each study site and was prescribed and monitored according to national guidelines.
Experimental: delayed group; In the delayed group, continuous renal replacement therapies 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.	Procedure: continuous renal replacement therapies; The choice of the method of continuous renal replacement therapy (device setting and anticoagulation method) is left to the discretion of each study site and was prescribed and monitored according to national guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall mortality	overall survival measured from randomization to death or day 90	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
recovery rate of renal function	the recovery rate of renal function will be compared between groups	90 days
organ dysfunction	the frequency of occurrence at least one organ dysfunction besides the kidney	90 days
length of ICU stay and in-hospital stay	average length of ICU stay and in-hospital stay will be compared	90 days
the percentage of receipt of CRRT at least once in the delayed group	the percentage of receipt of CRRT at least once in the delayed group	90 days
the number of days alive without CRRT, mechanical ventilation and vasopressor	the numbers of CRRT-free days, mechanical ventilation-free days and vasopressor-free days, between D0 and up to D90	90 days
difference of the Sequential Organ Failure Assessment score	difference of the Sequential Organ Failure Assessment (SOFA) score (0~24) at day 0, 1, 3, 7, 14 and day 28 between groups. Higher score means more illness.	28 days
the rate of complications potentially related to CRRT	the rate of complications potentially related to CRRT	90 days

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Guangzhou Medical University
• Investigators: Study Director: Xu-ming Xiong, PHD, Second Affiliated Hospital of Guangzhou Medical University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2019
• Primary Completion (Anticipated): August 21, 2023
• Study Completion (Anticipated): August 21, 2024

Study Registration Dates

• First Submitted: June 1, 2017
• First Submitted That Met QC Criteria: June 1, 2017
• First Posted (Actual): June 5, 2017

Study Record Updates

• Last Update Posted (Actual): December 22, 2021
• Last Update Submitted That Met QC Criteria: December 21, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: ICU-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No