Effects of HIgh Volume COntinuous REnal Replacement Therapy in Patients With Septic Acute Kidney Injury
Condition: Sepsis; Kidney Failure, Acute; Renal Replacement Therapy
MeSH terms: Acute Kidney Injury; Renal Insufficiency
Study type: Interventional

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.
    


Intervention name(s): high dose CRRT; Conventional dose CRRT
Intervention type(s): Drug; Drug
Intervention description(s): clearance of 80 mL/Kg/hr (1:1 balanced pre-dilution CVVHDF); clearance of 40 mL/Kg/hr (1:1 balanced pre-dilution CVVHDF)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment