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

This study has been completed.
Gambro Renal Products, Inc.
Information provided by (Responsible Party):
Dong Ki Kim, Seoul National University Hospital Identifier:
First received: August 29, 2010
Last updated: August 18, 2015
Last verified: August 2015

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.

Condition Intervention
Kidney Failure, Acute
Renal Replacement Therapy
Drug: high dose CRRT
Drug: Conventional dose CRRT

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of HIgh Volume COntinuous REnal Replacement Therapy in Patients With Septic Acute Kidney Injury

Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • Overall mortality [ Time Frame: 0 to 28 days ]

Secondary Outcome Measures:
  • 60-day mortality [ Time Frame: 0 to 60 days ]
  • 90-day mortality [ Time Frame: 0 to 90 days ]
  • ICU mortality [ Time Frame: 0 to 90 days ]
  • In-hospital mortality [ Time Frame: 0 to 90 days ]
  • duration of CRRT [ Time Frame: 0 to 90 days ]
  • duration of renal replacement therapy [ Time Frame: 0 to 90 days ]
  • duration of mechanical ventilation [ Time Frame: 0 to 90 days ]
  • cytokine removal rate [ Time Frame: 0 to 12h ]
  • changes in SOFA and APACHE II score [ Time Frame: 0 to 72 hr ]
  • hemofilter circuit life [ Time Frame: 0 to 72 hr] ]

Enrollment: 212
Study Start Date: January 2011
Study Completion Date: July 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High dose CRRT
Clearance of 80 mL/Kg/hr (1:1 balanced pre-dilution CVVHDF)
Drug: high dose CRRT
clearance of 80 mL/Kg/hr (1:1 balanced pre-dilution CVVHDF)
Active Comparator: Conventional dose CRRT
clearance of 40 mL/Kg/hr (1:1 balanced pre-dilution CVVHDF)
Drug: Conventional dose CRRT
clearance of 40 mL/Kg/hr (1:1 balanced pre-dilution CVVHDF)


Ages Eligible for Study:   20 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01191905

Korea, Republic of
National Health Insurance Corporation Ilsan Hospital
Koyang, Korea, Republic of, 410-719
Seoul National University Bundang Hospital
Seongnam city, Korea, Republic of, 463-707
Seoul National University Hospital
Seoul, Korea, Republic of, 110-752
Severance Hospital
Seoul, Korea, Republic of, 120-752
Seoul National University Boramae Medical Center
Seoul, Korea, Republic of, 156-707
Sponsors and Collaborators
Seoul National University Hospital
Gambro Renal Products, Inc.
Study Chair: Tae-Hyun Yoo, MD, PhD Yonsei University
Principal Investigator: Dong Ki Kim, MD, PhD Seoul National University Hospital
  More Information

Responsible Party: Dong Ki Kim, M.D, PhD, Seoul National University Hospital Identifier: NCT01191905     History of Changes
Other Study ID Numbers: SSGAM-001
Study First Received: August 29, 2010
Last Updated: August 18, 2015

Additional relevant MeSH terms:
Acute Kidney Injury
Renal Insufficiency
Kidney Diseases
Urologic Diseases processed this record on April 28, 2017