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

NCT01191905 | Completed DMC

• 1 other identifier: SSGAM-001
• Study Type: interventional
• Target: 212
• Locations: 1 country
• Sites: 5

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.

Conditions

Sepsis; Kidney Failure, Acute; Renal Replacement Therapy

Outcome Measures

Primary Outcomes (1)

• Overall mortality

  0 to 28 days

Secondary Outcomes (10)

• 60-day mortality

  0 to 60 days

• 90-day mortality

  0 to 90 days

• ICU mortality

  0 to 90 days

• In-hospital mortality

  0 to 90 days

• duration of CRRT

  0 to 90 days

Study Arms (2)

High dose CRRT

EXPERIMENTAL

Clearance of 80 mL/Kg/hr (1:1 balanced pre-dilution CVVHDF)

Drug: high dose CRRT

Conventional dose CRRT

ACTIVE COMPARATOR

clearance of 40 mL/Kg/hr (1:1 balanced pre-dilution CVVHDF)

Drug: Conventional dose CRRT

Interventions

high dose CRRT DRUG

clearance of 80 mL/Kg/hr (1:1 balanced pre-dilution CVVHDF)

High dose CRRT

Conventional dose CRRT DRUG

clearance of 40 mL/Kg/hr (1:1 balanced pre-dilution CVVHDF)

Conventional dose CRRT

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Gambro Renal Products, Inc.: collaborator

Study Sites (5)

National Health Insurance Corporation Ilsan Hospital

Koyang, 410-719, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, 463-707, South Korea

Location

Seoul National University Hospital

Seoul, 110-752, South Korea

Location

Severance Hospital

Seoul, 120-752, South Korea

Location

Seoul National University Boramae Medical Center

Seoul, 156-707, South Korea

Location

Related Publications (2)

• Fayad AI, Buamscha DG, Ciapponi A. Timing of kidney replacement therapy initiation for acute kidney injury. Cochrane Database Syst Rev. 2022 Nov 23;11(11):CD010612. doi: 10.1002/14651858.CD010612.pub3.

  PMID: 36416787 DERIVED

• 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.

  PMID: 34519356 DERIVED

MeSH Terms

Conditions

Sepsis; Acute Kidney Injury

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Tae-Hyun Yoo, MD, PhD

  Yonsei University

  STUDY CHAIR

• Dong Ki Kim, MD, PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D, PhD

Study Record Dates

• First Submitted: August 29, 2010
• First Posted: August 31, 2010
• Study Start: January 1, 2011
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: August 19, 2015

Record last verified: 2015-08

Locations

KR (5)