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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Seoul National University Hospital
Sponsor:
Collaborator:
Gambro Renal Products, Inc.
Information provided by (Responsible Party):
Dong Ki Kim, Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01191905
First received: August 29, 2010
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • Overall mortality [ Time Frame: 0 to 28 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 60-day mortality [ Time Frame: 0 to 60 days ] [ Designated as safety issue: No ]
  • 90-day mortality [ Time Frame: 0 to 90 days ] [ Designated as safety issue: No ]
  • ICU mortality [ Time Frame: 0 to 90 days ] [ Designated as safety issue: No ]
  • In-hospital mortality [ Time Frame: 0 to 90 days ] [ Designated as safety issue: No ]
  • duration of CRRT [ Time Frame: 0 to 90 days ] [ Designated as safety issue: No ]
  • duration of renal replacement therapy [ Time Frame: 0 to 90 days ] [ Designated as safety issue: No ]
  • duration of mechanical ventilation [ Time Frame: 0 to 90 days ] [ Designated as safety issue: No ]
  • cytokine removal rate [ Time Frame: 0 to 12h ] [ Designated as safety issue: No ]
  • changes in SOFA and APACHE II score [ Time Frame: 0 to 72 hr ] [ Designated as safety issue: No ]
  • hemofilter circuit life [ Time Frame: 0 to 72 hr] ] [ Designated as safety issue: No ]

Estimated Enrollment: 218
Study Start Date: January 2011
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: December 2013 (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)

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01191905

Contacts
Contact: Dong Ki Kim, MD, PhD. 82-2-2072-2303 dkkim73@gmail.com

Locations
Korea, Republic of
National Health Insurance Corporation Ilsan Hospital Recruiting
Koyang, Korea, Republic of, 410-719
Contact: Tae Ik Chang, MD    82-31-900-0246    tichang@hanmail.net   
Seoul National University Bundang Hospital Not yet recruiting
Seongnam city, Korea, Republic of, 463-707
Contact: Sejoong Kim, MD, PhD    82-2-11-9196-5245    imsejoong@hanmail.net   
Seoul National University Boramae Medical Center Active, not recruiting
Seoul, Korea, Republic of, 156-707
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-752
Contact: Hajeong Lee, MD    82-10-8647-6524    dewyhj@hanmail.net   
Severance Hospital Recruiting
Seoul, Korea, Republic of, 120-752
Contact: Jung Tak Park, MD    82-2-2228-5345    jtpark@yuhs.ac   
Sponsors and Collaborators
Seoul National University Hospital
Gambro Renal Products, Inc.
Investigators
Study Chair: Tae-Hyun Yoo, MD, PhD Yonsei University
Principal Investigator: Dong Ki Kim, MD, PhD Seoul National University Hospital
  More Information

No publications provided

Responsible Party: Dong Ki Kim, M.D, PhD, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01191905     History of Changes
Other Study ID Numbers: SSGAM-001
Study First Received: August 29, 2010
Last Updated: December 12, 2013
Health Authority: South Korea: Institutional Review Board

Additional relevant MeSH terms:
Acute Kidney Injury
Renal Insufficiency
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on November 20, 2014