Effects of HIgh Volume COntinuous REnal Replacement Therapy in Patients With Septic Acute Kidney Injury

Sepsis Clinical Trial

— HICORES  

Official title:

Effects of HIgh Volume COntinuous REnal Replacement Therapy in Patients With Septic Acute Kidney Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01191905
• Other study ID #: SSGAM-001
• Status: Completed
• Phase: N/A
• First received: August 29, 2010
• Last updated: August 18, 2015
• Start date: January 2011
• Est. completion date: July 2015

Study information

• Verified date: August 2015
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 212
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Kidney Injury
• Kidney Failure, Acute
• Renal Insufficiency
• Renal Replacement Therapy
• Sepsis

Intervention

Drug:
• high dose CRRT
clearance of 80 mL/Kg/hr (1:1 balanced pre-dilution CVVHDF)
• Conventional dose CRRT
clearance of 40 mL/Kg/hr (1:1 balanced pre-dilution CVVHDF)

Locations

Country	Name	City	State
Korea, Republic of	National Health Insurance Corporation Ilsan Hospital	Koyang
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam city
Korea, Republic of	Seoul National University Boramae Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Gambro Renal Products, Inc.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall mortality		0 to 28 days	No
Secondary	60-day mortality		0 to 60 days	No
Secondary	90-day mortality		0 to 90 days	No
Secondary	ICU mortality		0 to 90 days	No
Secondary	In-hospital mortality		0 to 90 days	No
Secondary	duration of CRRT		0 to 90 days	No
Secondary	duration of renal replacement therapy		0 to 90 days	No
Secondary	duration of mechanical ventilation		0 to 90 days	No
Secondary	cytokine removal rate		0 to 12h	No
Secondary	changes in SOFA and APACHE II score		0 to 72 hr	No
Secondary	hemofilter circuit life		0 to 72 hr]	No