Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effects of HIgh Volume COntinuous REnal Replacement Therapy in Patients With Septic Acute Kidney Injury
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.


Options:
A: Inclusion Criteria:

* Intensive care patients scheduled for continuous venovenous hemofiltration

Exclusion Criteria:

* Severe pre-existent liver failure (cirrhosis Child C), acute liver dysfunction as occurring with septic shock is not a reason for exclusion
* Active bleeding or bleeding necessitating the infusion of two red blood cell units within 24 hours before starting hemofiltration or a fall in hemoglobin of \> 0.5 mmol/l. A fall in hemoglobin/hematocrit as a result of fluid loading is not regarded as bleeding.
* Surgery within 24 h prior to CVVH.
* Patients needing full systemic anticoagulation (unfractionated heparin in a dose of \> 10000 IU/day, or nadroparin \> 3800 IU/day) for other reasons
* Expectation to die within 24 hours
* Chronic dialysis
* Proven or suspected heparin-induced thrombocytopenia
B: 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
C: Inclusion Criteria:

* Need for hemodialysis in the ICU for at least one treatment
* No prior hemodialysis treatment in the ICU except continuous renal replacement therapy

Exclusion Criteria:

* Need for systemic anticoagulation with unfractionated or fractionated heparin, oral anticoagulants or intravenous anti-aggregants for other reasons
* Need for continued thrombolysis therapy within the 6 hours before inclusion
* Need for continued treatment with activated protein C (drotrecogin alfa) within the 12 hours before inclusion
* Need for continued treatment with intravenous anti-aggregants (abciximab, eptifabide) within 12 hours before inclusion
* Liver failure (acute and acute-on-chronic)
* Confirmed or suspected Heparin Induced Thrombocytopenia (HIT)
* Heparin allergies
* Severe uncorrected hypocalcemia (ionized calcium \< 0,8 mmol/l)
* Refusal of informed consent
D: Inclusion Criteria:

1. Patients admitted to intensive care unit (ICU) of age \>18 years with decision based on the clinical situation of the patient taken by the physician in charge that continuous renal replacement therapy will be started.
2. Vasoconstrictor and volume dependent septic shock with known Gram-negative infectious agent in blood culture.
3. Vasoconstrictor and volume dependent septic shock suspected to be caused by a Gram-negative agent and with positive plasma endotoxin test.

Exclusion Criteria:

1. Infected with Hepatitis B or C or HIV.
2. Dependence on dialysis treatment before the actual ICU episode.

Answer: B