Low-intensity Versus Medium-intensity Continuous Kidney Replacement Therapy for Critically Ill Patients

Study Overview
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Brief Summary
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This clinical trial aims to investigate whether the low treatment intensity (12 mL/kg/hr, low-dose hemodialysis/filtration) or the medium treatment intensity (25 mL/kg/hr, standard-dose hemodialysis/filtration) is more effective and safer for continuous renal replacement therapy in critically ill patients.

Official Title
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Low-Intensity Versus Medium-Intensity Continuous Kidney Replacement Therapy for Critically Ill Patients (LIMIT): A Multicenter Randomized Clinical Trial

Conditions
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Acute Kidney Injury Requiring Continuous Renal Replacement Therapy

Intervention / Treatment
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* Drug: Dialysate fluid, Filtration replacement fluid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient who meets all of the following criteria and who has given informed consent. Adults (18 years of age or older, regardless of the time since ICU admission) currently admitted to an intensive care unit*. *Includes high care units, where continuous monitoring is conducted and intensive care physicians are in charge of medical care. A diagnosis of acute kidney injury is made according to the Kidney Disease: Improving Global Outcomes (KDIGO) international diagnostic criteria (one of the following is met) Serum creatinine increased by more than 0.3 mg/dL within 48 hours Serum creatinine increased more than 1.5-fold from baseline and the increase is considered to have occurred within 7 days Oliguria (< 0.5 mL/kg/hr) lasting more than 6 hours The treating intensivist believes that continuous kidney replacement therapy is necessary Exclusion Criteria: Patient who meets any of the following exclusion criteria will be excluded. Receiving chronic dialysis or scheduled for initiation of chronic dialysis Undergoing any kidney replacement therapy or blood purification therapy within 48 hours When kidney replacement therapy using other dialysate or replacement fluids, such as citrate dialysis, is preferred due to coexisting bleeding disorders or allergy to acetate Concomitant blood purification therapy other than hemofiltration/dialysis, such as plasma exchange The patient is in a very critical condition and the treating physician believes that survival for more than 24 hours is unlikely Previous participation in the study After receiving a full explanation of the study and with full understanding, a patient do not consent to participate in the study of their own (or their substitute decision maker's) will. The principal investigator (or an investigator) thinks it to be inappropriate to participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low intensity<br>12 mL/kg/hr | Drug: Dialysate fluid, Filtration replacement fluid<br>* Dose of continuous hemodialysis and/or hemofiltration<br>|
| Active Comparator: Medium intensity<br>25 mL/kg/hr | Drug: Dialysate fluid, Filtration replacement fluid<br>* Dose of continuous hemodialysis and/or hemofiltration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day kidney replacement therapy free days | Composite endpoint of death and duration of kidney replacement therapy at 28 days | 28 days or hospital discharge whichever comes first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU mortality |  | 90 days or hospital discharge whichever comes first | 
| Hospital mortality |  | 90 days or hospital discharge whichever comes first | 
| Dialysis dependence at hospital discharge |  | 90 days or hospital discharge whichever comes first | 
| 28-day vasopressor-free days |  | 28 days or hospital discharge whichever comes first | 
| 28-day ventilator-free days |  | 28 days or hospital discharge whichever comes first | 
| Serum creatinine level at the end of kidney replacement therapy | Serum creatinine level on the day of final kidney replacement therapy and the day before | 90 days or hospital discharge whichever comes first | 
| 24-hour urine output at the end of kidney replacement therapy | 24-hour urine output on the day of final kidney replacement therapy and the day before | 90 days or hospital discharge whichever comes first |