On Demand Versus Protocol-guided Renal Replacement Therapy for Management of Stage 3 Acute Kidney Injury in Patients With Cirrhosis

Study Overview
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Brief Summary
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Intervention: All patients at presentation would be assessed for the underlying cause of and will be managed by removal of all precipitants(careful review of medications, diuretics, nephrotoxic drugs,vasodilators or non-steroidal anti-inflammatory drugs). The second step would be to consider plasma volume expansion in patients with hypovolemia (the choice of fluid could either be a crystalloid or albumin or even blood as indicated) along with identification and early treatment of bacterial infections. Along with this patients with a differential diagnosis of HRS-AKI would be given terlipressin ( or noradrenaline/octreotide midodrine in case of contraindication to terlipressin). Patients with a clinical diagnosis of ATN would be randomized to the on-demand versus protocol-guided dialysis groups. Further, patients with urine output of less than 0.5ml/kg/hour for 4-6 hours despite adequate fluid resuscitation and vasoconstrictors would also be subjected to randomization. In the on-demand group patients would get dialysis only when patient fulfills absolute criteria requiring dialysis such as metabolic acidosis with ph<7.2, hyperkalemia, refractory fluid overload (non-responsive to diuretics) or oliguria with urine output of less than 0.5ml/kg for more than 24-48 hours from the time of randomization In the protocol guided group patients all patients would be considered for dialysis within 6 hours of randomization After randomization patients would receive dialysis as three sessions per week of at least 4 h with a blood flow >200 mL/min and a dialysate flow >500 mL/min in intermittent group and as 20-25 mL/kg/h of effluent, by filtration and/or diffusion in continuous form until recovery of renal functions

Official Title
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On Demand Versus Protocol-guided Renal Replacement Therapy for Management of Stage 3 Acute Kidney Injury in Patients With Cirrhosis -A Prospective Randomized Controlled Trial

Conditions
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Acute Kidney Injury With Cirrhosis

Intervention / Treatment
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* Biological: Protocol Guided Renal Replacement Therapy
* Biological: On Demand Renal Replacement Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with cirrhosis (diagnosed based on clinical, biochemical,radiological or histological diagnosis) with stage 3 Acute Kidney Injury defined as an increase of serum creatinine to more than 300 fold and more than 4 mg/dl. Exclusion Criteria: Patients with age less than 18 years Severe known cardiopulmonary disease (structural or valvular heart disease, coronary artery disease, COPD Chronic Obstructive Pulmonary Disease) Pregnancy Chronic kidney disease on hemodialysis Patients with post renal obstructive AKI (Acute Kidney Injury), AKI (Acute Kidney Injury) suspected due to glomerulonephritis, interstitial nephritis or vasculitis based on clinical history and urine analysis Patients already meeting emergency criteria for immediate hemodialysis at the time of randomization (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
Maximum Age: 65 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: Protocol Guided-RRT<br>In the on-demand group patients would get dialysis only when patient fulfills absolute criteria requiring dialysis such as metabolic acidosis with ph<7.2, hyperkalemia, refractory fluid overload (non-responsive to diuretics) or oliguria with urine output of less than 0.5ml/kg for more than 24-48 hours from the time of randomization. | Biological: Protocol Guided Renal Replacement Therapy<br>* In the on-demand group patients would get dialysis only when patient fulfills absolute criteria requiring dialysis such as metabolic acidosis with ph<7.2, hyperkalemia, refractory fluid overload (non-responsive to diuretics) or oliguria with urine output of less than 0.5ml/kg for more than 24-48 hours from the time of randomization.<br>|
| Active Comparator: On Demand-RRT<br>In the protocol guided group patients all patients would be considered for dialysis within 6 hours of randomization After randomization patients would receive dialysis as three sessions per week of at least 4 h with a blood flow >200 mL/min and a dialysate flow >500 mL/min in intermittent group and as 20-25 mL/kg/h of effluent, by filtration and/or diffusion in continuous form until recovery of renal functions | Biological: On Demand Renal Replacement Therapy<br>* Patients to be randomized to the intervention as per standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recovery of renal functions in both groups |  | day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse effects of dialysis in the first session in both groups |  | 48 hours | 
| Improvement in SOFA (by 2 points) scores in both groups |  | 48 hours | 
| Improvement in MELD ( by 2 points) scores in both groups |  | 48 hours | 
| Improvement in APACHE ( by 2 points) scores in both groups |  | 48 hours | 
| Change to End Stage Renal Disease with requirement of maintenance hemodialysis at least twice a week in both groups |  | 4 weeks | 
| Improvement in renal functions in both groups |  | 7 days | 
| Mortality in both groups |  | 1 month | 
| Mortality in both groups |  | 3 month | 
| Response to vasoconstrictors in patients with Hepatorenal Syndrome-Acute Kidney Injury in both groups. | Response as assessed by either improvement in urine output >0.5ml/kg/hour, acid-base status or renal functions. | 6 hours | 
| Response to vasoconstrictors in patients with Hepatorenal Syndrome-Acute Kidney Injury in both groups. | Response as assessed by either improvement in urine output >0.5ml/kg/hour, acid-base status or renal functions. | 12 hours | 
| Response to vasoconstrictors in patients with Hepatorenal Syndrome-Acute Kidney Injury | Response as assessed by either improvement in urine output >0.5ml/kg/hour, acid-base status or renal functions. | 24 hours | 
| Response to vasoconstrictors in patients with Hepatorenal Syndrome-Acute Kidney Injury in both groups | Response as assessed by either improvement in urine output >0.5ml/kg/hour, acid-base status or renal functions. | 24 hours |