Early Versus Late CRRT in ACLF Patients With Septic Shock and AKI

Study Overview
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Brief Summary
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Consecutive patients with ACLF (Acute on Chronic Liver Failure) and septic shock with AKI (Acute Kidney Injury) who give written informed consent will be included in this prospective trial at ILBS. At baseline s, endotoxin levels, NT-Pro BNP, , urine N-GAL will be done for all patients. A 10 ml serum sample will be stored for doing a cytokine profile. Septic shock will be defined by the presence of two or more diagnostic criteria for the systemic inflammatory response syndrome, proven or suspected infection with hypotension non-responsive to adequate fluid resuscitation assessed by no evidence of stroke volume variation on flow track and need of a vasopressor to achieve a target mean arterial pressure (MAP) of ≥ 65 mm Hg. A record of CVP, IVC diameter and B-lines on ultrasound lung would also be done. Patients with age less than 18 years, severe known cardiopulmonary disease (structural or valvular heart disease, coronary artery disease, COPD) pregnancy, chronic kidney disease, patients already meeting emergency criteria for immediate hemodialysis at the time of randomization as specified in the late group, patients transferred from other hospitals who have already been on hemodialysis before their arrival in the intensive care unit, extremely moribund patients with an expected life expectancy of less than 24 hours, failure to give informed consent from family members.

Official Title
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Early Versus Late CRRT (Continuous Renal Replacement Therpay) in ACLF (Acute on Chronic Liver Failure) Patients With Septic Shock and AKI (Acute Kidney Injury) - A Randomized Controlled Trial

Conditions
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Septic Shock and Acute Kidney Injury

Intervention / Treatment
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* Other: Early CRRT
* Other: Late CRRT
* Other: Standard Medical Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Patients with ACLF defined based on APASL criteria with septic shock associated AKI Exclusion Criteria: Patients with age less than 18 years Severe known cardiopulmonary disease (structural or valvular heart disease, coronary artery disease, COPD) Pregnancy Chronic kidney disease on hemodialysis Patients with Hepatorenal Syndrome, post renal obstructive AKI, AKI due to glomerulonephritis, interstitial nephritis or vasculitis Patients already meeting emergency criteria for immediate hemodialysis at the time of randomization as specified in the late group (serum potassium>6 meq/lt, metabolic acidosis ph<7.12, acute pulmonary edema, severe volume overload with hypoxemia non-responsive to diuretic treatment) Patients transferred from other hospitals who have already been on hemodialysis before their arrival in the intensive care unit Extremely moribund patients with an expected life expectancy of less than 24 hours Failure to give informed consent from family members. Hemodynamic instability requiring very high dose of vasopressors

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: Early CRRT<br>Early Continous Renal Replacement Therapy within 6 hours + Standard Medical Therapy | Other: Early CRRT<br>* Continous Renal Replacement Therapy<br>Other: Standard Medical Therapy<br>* Standard Medical Therapy<br>|
| Active Comparator: Late CRRT<br>Late Continous Renal Replacement Therapy + Standard Medical Therapy | Other: Late CRRT<br>* Continous Renal Replacement Therapy<br>Other: Standard Medical Therapy<br>* Standard Medical Therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplant Free Survival |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of intradialytic hypotension i.e. defined as a decrease in systolic blood pressure by ≥20 mm Hg or a decrease in MAP by 10 mm Hg associated with symptoms |  | 1 year | 
| Hemodynamic stability i.e. maintenance of MAP on dialysis without increase in the vasopressors |  | 1 year | 
| Dialysis efficiency as measured by Urea Reduction ratio at 48 hours |  | 2 days | 
| Achievement of target ultrafiltration goals |  | 1 year | 
| Recovery in renal functions defined as an increase in urine output to more than 400 ml/day |  | 1 year | 
| Duration of mechanical ventilation and ICU (Intensive Care Unit) stay |  | 1 year | 
| Improvement in SOFA (Sequential Organ Failure Assessment ) ( by 2 points) scores |  | 1 year | 
| Improvement in APACHE (Acute Physiology and Chronic Health Evaluation) ( by 2 points) scores |  | 1 year | 
| Improvement in MELD (Model for End Stage Liver Disease) ( by 2 points) scores |  | 1 year | 
| Improvement in lactic acidosis and lactate clearance at 6 hours after initiation of CRRT |  | within 6 hours | 
| Improvement in lactic acidosis and lactate clearance at 12 hours after initiation of CRRT |  | within 12 hours | 
| Improvement in lactic acidosis and lactate clearance at 24 hours after initiation of CRRT |  | within 24 hours |