Clinical trial NCT01191905: Effects of HIgh Volume COntinuous REnal Replacement Therapy in Patients With Septic Acute Kidney Injury
Official title: Effects of HIgh Volume COntinuous REnal Replacement Therapy in Patients With Septic Acute Kidney Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Kidney Failure, Acute
Renal Replacement Therapy
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Gambro Renal Products, Inc.
First posted: 2010-08-31
Enrollment: 212
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Acute kidney injury (AKI) is a common and serious problem in critically ill patients, and is known to be an independent risk factor for mortality. Among the various etiologies of AKI, sepsis or septic shock is the most frequent contributing factor especially in an intensive care unit setting. Also, the mortality of septic AKI in these patients still remains extremely high despite recent marked therapeutic advance.

Given the physiologic superiority of continuous renal replacement therapy (CRRT) on uremia and volume control, it has become the modality of choice in critically ill patients with AKI. In addition, CRRT can theoretically provide immunohomeostasis through the convective and adsorptive removal of various immune mediators. Although the pathophysiology of septic AKI remains elusive, it has become increasingly recognized that many pro- and anti-inflammatory mediators, such as TNF, IL-6, IL-8 and IL-10, play an important role in this process. Therefore, it has been speculated that the reduction of cytokines by increasing CRRT dose in patients with septic AKI may reduce mortality risk. Even though recent two large scale randomized controlled trials, ATN and RENAL study, have failed to show the difference in survival rate between the clearance of 20\~25 ml/kg/hr and 35\~40 ml/kg/hr, none of these studies were designed to elucidate the survival benefit of high intensity CRRT in patients with septic AKI. Moreover, the optimal target CRRT dose in these patients is not well established and may be even higher than 35\~40 ml/kg/hr in terms of septic AKI. Indeed, recent several uncontrolled trial have shown the survival benefit of high intensity CRRT in these patients.

To further explore the effects of high dose CRRT on survival of critically ill patients with septic AKI, the investigators will conduct a multicenter prospective randomized controlled open-label trial which compares the difference in survival rate between 1:1 balanced pre-dilution CVVHDF at 80 vs. 40 mL/Kg/hr for initial 72hrs after the start of CRRT. The primary end-point of this study is the effect of high volume pre-dilution CVVHDF on 28-day survival rate. The secondary end-point is 60- and 90-day mortality, ICU and in-hospital mortality, duration of CRRT and renal replacement therapy, duration of mechanical ventilation, cytokine removal rate at 12h after the initiation of CRRT, and changes in SOFA and APACHE II score at 72h after the initiation of CRRT. This is a superiority trial which aims to demonstrate a reduction of 20% or more in mortality rate. For this purpose, at least 109 subjects (a total of 218) would be required for each group if type I error rate is 5% and type II error is 20% given 25% of drop-out rate during the study period. Block randomization will be used by means of a dedicated website.

There are still conflicting data on the optimal target dose of CRRT in patients with septic AKI. Our study will address this issue to answer the unresolved question on the effect of high dose CRRT.


Eligibility criteria: Inclusion Criteria:

* Consensus criteria for sepsis
* Injury stage of RIFLE criteria or more (\>2-fold increase in the serum creatinine or urine output \<0.5 mL/kg/hr for 12 hours)
* Absence of other established non-sepsis-related cause of AKI
* written informed consent

Exclusion Criteria:

* patient age \< 20 years or \> 80 years
* life expectancy less than 3 months (ex. terminal stage of malignancy)
* Child-Pugh class C liver cirrhosis
* Pregnancy or lactation
* History of dialysis prior to the randomization

Primary outcomes:
measure: Overall mortality
timeFrame: 0 to 28 days
Secondary outcomes:
measure: 60-day mortality
timeFrame: 0 to 60 days
measure: 90-day mortality
timeFrame: 0 to 90 days
measure: ICU mortality
timeFrame: 0 to 90 days
measure: In-hospital mortality
timeFrame: 0 to 90 days
measure: duration of CRRT
timeFrame: 0 to 90 days
measure: duration of renal replacement therapy
timeFrame: 0 to 90 days
measure: duration of mechanical ventilation
timeFrame: 0 to 90 days
measure: cytokine removal rate
timeFrame: 0 to 12h
measure: changes in SOFA and APACHE II score
timeFrame: 0 to 72 hr
measure: hemofilter circuit life
timeFrame: 0 to 72 hr]
Other outcomes:
Locations:
city: Koyang
country: Korea, Republic of
facility: National Health Insurance Corporation Ilsan Hospital
city: Seongnam city
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Boramae Medical Center
Study officials:
affiliation: Yonsei University
name: Tae-Hyun Yoo, MD, PhD
role: STUDY_CHAIR
affiliation: Seoul National University Hospital
name: Dong Ki Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tsujimoto Y, Miki S, Shimada H, Tsujimoto H, Yasuda H, Kataoka Y, Fujii T. Non-pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2021 Sep 14;9(9):CD013330. doi: 10.1002/14651858.CD013330.pub2.