Sustained Low Efficiency Dialysis Versus Continuous Renal Replacement Therapy for Acute Kidney Injury in Critically Ill Cirrhotics
Condition: Liver Cirrhosis
MeSH terms: Liver Cirrhosis; Acute Kidney Injury
Study type: Interventional

Summary: 
      The current prospective pliot randomized controlled trial has been designed to demonstrate
      non-inferiority of sustained low efficiency dialysis (SLED) when compared to continuous renal
      replacement therapy in managing AKI in context of cirrhotics with septic shock who are
      hemodynamically unstable. The patients would be randomized 1:1 to either SLED or CRRT after
      screening for the inclusion and exclusion criteria.
    

Detailed description: 
      Aim & Objectives

      Primary objective To study the efficacy of sustained low efficiency dialysis versus
      continuous renal replacement therapy in cirrhotics with septic shock and severe AKI

      Secondary Objectives Effects on renal recovery rates in the two groups To assess the effects
      on 7-day and 28-day mortality Efficacy on Lactate Clearance Duration of mechanical
      ventilation and ICU stay Effect on systemic hemodynamics and reversal of shock Clearance of
      endotoxin and pro-inflammatory cytokines Effect on coagulation and endothelial function
      Improvement in SOFA scores at 48 hours and day 5

      Methodology All included patients would be randomised to receive either continuous renal
      replacement therapy or sustained low efficiency dialysis (SLED) Patients with septic shock
      would be screened. Following this, patients meeting the inclusion and exclusion criteria will
      be screened and randomized to the two treatment groups. Standard criteria will be considered
      to define refractoriness to fluids and initiation of dialysis. Fluid management would be
      performed using the dynamic indices in patients on mechanical ventilation or using IVC
      diameter and passive-leg rasing in non-intubated patients. In all patients, baseline
      endotoxin activity assay and blood and urine sample will be stored for looking at the effect
      of therapy on cytokine profile (TNF alpha, IL-IB, IL6, IFN-gamma, MCP-1, IL-10 and ADAMTS and
      vWillebrand factor). Septic shock would be defined as a clinical construct of sepsis with
      persisting hypotension requiring vasopressors to maintain MAP>=65 mm of Hg and having a serum
      lactate >2 mmol/L despite adequate volume resuscitation. The blood flow rate, dialysis flow
      rate and need of ultrafiltration would be recorded for all enrolled patients. Subsequent
      sessions of therapy would be done as per requirement and recorded. The dose of vasopressor in
      norepinephrine equivalent would be recorded for all patients at enrolment as under

      Study Population:

      Patients with cirrhosis with septic shock and AKI requiring dialysis

      Indications for initiation of dialysis

        1. Metabolic acidosis with ph<7.2 or serum bicarbonate <15 mEq/lt

        2. Hyperkalemia with serum potassium >5.5 Meq/L non-responsive to standard treatment

        3. Oliguria with or without fluid overload (non-responsive to diuretics) with urine output
           of less than 0.5ml/kg/hr despite fluid resuscitation

        4. Uremic complications (encephalopathy, pericarditis etc.)

      Study Design:

        -  A randomized controlled study- Non-inferiority trial

        -  The study will be conducted on patients admitted to Department of Hepatology from June
           2020 to December 2020 at ILBS, New Delhi

        -  Study group will comprise critically ill patients with cirrhosis with septic shock and
           AKI requiring dialysis

      Study Period: The study will be conducted on patients admitted to Department of Hepatology
      from May 2020 to December 2020 at ILBS, New Delhi

      Sample Size Calculation: The study will be designed as a pilot RCT with an aim to enrol 25
      patients in each group. At completion a decision for termination versus continuation of the
      study would be taken.

      Intervention: CRRT versus SLED until renal recovery

      Renal recovery would be defined as increase in urine output to more than 400ml/day in
      patients with anuria, resolution of metabolic complications or spontaneous decline in urea
      and creatinine necessitating stopping dialytic support

      Monitoring and Assessment: Hourly till the patient is in the intensive care then every 7 days
      until day 28

      Statistical analysis

        -  All variables shall be expressed in mean (sd) or median (range)

        -  Variables will be compared by Mann- Whitney U test

        -  For Categorical variables we will use Chi-Square or Fisher's test

        -  Survival analysis will be done using Cox-proportional regression analysis

      Actuarial probability of survival shall be calculated by Kaplan- Meier graph and compared by
      log- rank test.

      Adverse Effects: Worsening of hypotension, bleeding any cardiac side-effects, worsening
      lactate, hypothermia, bradycardia

      Stopping Rule: clinically relevant bleeding (i.e., transfusion requirements of at least 2
      units of packed red cells), arrythmias (brady or tachyarryhthmias), poorly tolerated
      supraventricular arrhythmia related blood stream infections, development of electrolyte
      abnormalities hypokalemia, hypophosphatemia or hypomagnesemia refractory to medical
      management, renal recovery
    

Intervention name(s): Sustained Low Efficiency Dialysis (SLED); Continuous Renal Replacement Therapy
Intervention type(s): Procedure; Procedure
Intervention description(s): sustained low efficiency dialysis (SLED); Continuous Renal Replacement Therapy
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment