<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04494542</url>
  </required_header>
  <id_info>
    <org_study_id>ILBS-Cirrhosis-36</org_study_id>
    <nct_id>NCT04494542</nct_id>
  </id_info>
  <brief_title>Sustained Low Efficiency Dialysis Versus Continuous Renal Replacement Therapy for Acute Kidney Injury in Critically Ill Cirrhotics</brief_title>
  <official_title>Sustained Low Efficiency Dialysis Versus Continuous Renal Replacement Therapy for Acute Kidney Injury in Critically Ill Cirrhotics-A Pilot Randomized Controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Liver and Biliary Sciences, India</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institute of Liver and Biliary Sciences, India</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current prospective pliot randomized controlled trial has been designed to demonstrate&#xD;
      non-inferiority of sustained low efficiency dialysis (SLED) when compared to continuous renal&#xD;
      replacement therapy in managing AKI in context of cirrhotics with septic shock who are&#xD;
      hemodynamically unstable. The patients would be randomized 1:1 to either SLED or CRRT after&#xD;
      screening for the inclusion and exclusion criteria.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aim &amp; Objectives&#xD;
&#xD;
      Primary objective To study the efficacy of sustained low efficiency dialysis versus&#xD;
      continuous renal replacement therapy in cirrhotics with septic shock and severe AKI&#xD;
&#xD;
      Secondary Objectives Effects on renal recovery rates in the two groups To assess the effects&#xD;
      on 7-day and 28-day mortality Efficacy on Lactate Clearance Duration of mechanical&#xD;
      ventilation and ICU stay Effect on systemic hemodynamics and reversal of shock Clearance of&#xD;
      endotoxin and pro-inflammatory cytokines Effect on coagulation and endothelial function&#xD;
      Improvement in SOFA scores at 48 hours and day 5&#xD;
&#xD;
      Methodology All included patients would be randomised to receive either continuous renal&#xD;
      replacement therapy or sustained low efficiency dialysis (SLED) Patients with septic shock&#xD;
      would be screened. Following this, patients meeting the inclusion and exclusion criteria will&#xD;
      be screened and randomized to the two treatment groups. Standard criteria will be considered&#xD;
      to define refractoriness to fluids and initiation of dialysis. Fluid management would be&#xD;
      performed using the dynamic indices in patients on mechanical ventilation or using IVC&#xD;
      diameter and passive-leg rasing in non-intubated patients. In all patients, baseline&#xD;
      endotoxin activity assay and blood and urine sample will be stored for looking at the effect&#xD;
      of therapy on cytokine profile (TNF alpha, IL-IB, IL6, IFN-gamma, MCP-1, IL-10 and ADAMTS and&#xD;
      vWillebrand factor). Septic shock would be defined as a clinical construct of sepsis with&#xD;
      persisting hypotension requiring vasopressors to maintain MAP&gt;=65 mm of Hg and having a serum&#xD;
      lactate &gt;2 mmol/L despite adequate volume resuscitation. The blood flow rate, dialysis flow&#xD;
      rate and need of ultrafiltration would be recorded for all enrolled patients. Subsequent&#xD;
      sessions of therapy would be done as per requirement and recorded. The dose of vasopressor in&#xD;
      norepinephrine equivalent would be recorded for all patients at enrolment as under&#xD;
&#xD;
      Study Population:&#xD;
&#xD;
      Patients with cirrhosis with septic shock and AKI requiring dialysis&#xD;
&#xD;
      Indications for initiation of dialysis&#xD;
&#xD;
        1. Metabolic acidosis with ph&lt;7.2 or serum bicarbonate &lt;15 mEq/lt&#xD;
&#xD;
        2. Hyperkalemia with serum potassium &gt;5.5 Meq/L non-responsive to standard treatment&#xD;
&#xD;
        3. Oliguria with or without fluid overload (non-responsive to diuretics) with urine output&#xD;
           of less than 0.5ml/kg/hr despite fluid resuscitation&#xD;
&#xD;
        4. Uremic complications (encephalopathy, pericarditis etc.)&#xD;
&#xD;
      Study Design:&#xD;
&#xD;
        -  A randomized controlled study- Non-inferiority trial&#xD;
&#xD;
        -  The study will be conducted on patients admitted to Department of Hepatology from June&#xD;
           2020 to December 2020 at ILBS, New Delhi&#xD;
&#xD;
        -  Study group will comprise critically ill patients with cirrhosis with septic shock and&#xD;
           AKI requiring dialysis&#xD;
&#xD;
      Study Period: The study will be conducted on patients admitted to Department of Hepatology&#xD;
      from May 2020 to December 2020 at ILBS, New Delhi&#xD;
&#xD;
      Sample Size Calculation: The study will be designed as a pilot RCT with an aim to enrol 25&#xD;
      patients in each group. At completion a decision for termination versus continuation of the&#xD;
      study would be taken.&#xD;
&#xD;
      Intervention: CRRT versus SLED until renal recovery&#xD;
&#xD;
      Renal recovery would be defined as increase in urine output to more than 400ml/day in&#xD;
      patients with anuria, resolution of metabolic complications or spontaneous decline in urea&#xD;
      and creatinine necessitating stopping dialytic support&#xD;
&#xD;
      Monitoring and Assessment: Hourly till the patient is in the intensive care then every 7 days&#xD;
      until day 28&#xD;
&#xD;
      Statistical analysis&#xD;
&#xD;
        -  All variables shall be expressed in mean (sd) or median (range)&#xD;
&#xD;
        -  Variables will be compared by Mann- Whitney U test&#xD;
&#xD;
        -  For Categorical variables we will use Chi-Square or Fisher's test&#xD;
&#xD;
        -  Survival analysis will be done using Cox-proportional regression analysis&#xD;
&#xD;
      Actuarial probability of survival shall be calculated by Kaplan- Meier graph and compared by&#xD;
      log- rank test.&#xD;
&#xD;
      Adverse Effects: Worsening of hypotension, bleeding any cardiac side-effects, worsening&#xD;
      lactate, hypothermia, bradycardia&#xD;
&#xD;
      Stopping Rule: clinically relevant bleeding (i.e., transfusion requirements of at least 2&#xD;
      units of packed red cells), arrythmias (brady or tachyarryhthmias), poorly tolerated&#xD;
      supraventricular arrhythmia related blood stream infections, development of electrolyte&#xD;
      abnormalities hypokalemia, hypophosphatemia or hypomagnesemia refractory to medical&#xD;
      management, renal recovery&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 25, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Development of intradialytic hypotension i.e. decrease in defined as a decrease in systolic blood pressure by ≥20 mm Hg or a decrease in MAP by 10 mm Hg after initiation of dialysis</measure>
    <time_frame>at 6 hours after dialysis initiation</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mortality in both groups</measure>
    <time_frame>Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of mechanical ventilation and ICU stay</measure>
    <time_frame>Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AKI recovery at day 14</measure>
    <time_frame>Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal failure related death at day 7</measure>
    <time_frame>Day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lactate clearance at 12 in both groups</measure>
    <time_frame>12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lactate clearance at 24 hours in both groups</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reversal of shock at 48 hours</measure>
    <time_frame>48 hours</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Liver Cirrhosis</condition>
  <arm_group>
    <arm_group_label>Sustained Low Efficiency Dialysis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sustained Low Efficiency Dialysis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continuous Renal Replacement Therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>continuous renal replacement therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sustained Low Efficiency Dialysis (SLED)</intervention_name>
    <description>sustained low efficiency dialysis (SLED)</description>
    <arm_group_label>Sustained Low Efficiency Dialysis</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Continuous Renal Replacement Therapy</intervention_name>
    <description>Continuous Renal Replacement Therapy</description>
    <arm_group_label>Continuous Renal Replacement Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Critically ill cirrhotics with septic shock defined as need of vasopressors to maintain&#xD;
        MAP&gt; 65 mm Hg and lacate &gt;2 mmol/L despite adequate fluid resuscitation with severe AKI&#xD;
        meeting criteria for dialysis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with age less than 18 years or more than 65 years&#xD;
&#xD;
          -  Severe known cardiopulmonary disease (structural or valvular heart disease, coronary&#xD;
             artery disease, COPD, CKD)&#xD;
&#xD;
          -  Patients with ACLF&#xD;
&#xD;
          -  Patients with cerebral edema&#xD;
&#xD;
          -  Patients with refractory shock i.e. requiring norepinephrine or equivalent&#xD;
             &gt;0.5ug/kg/min&#xD;
&#xD;
          -  Severe coagulopathy platelets &lt;20,000 and INR &gt;4&#xD;
&#xD;
          -  Active Bleed (Mucosal or variceal)&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Patients with moderate-severe ARDS i.e. Pa02/Fio2 ratio &lt;200&#xD;
&#xD;
          -  Extremely moribund patients with an expected life expectancy of less than 24 hours&#xD;
&#xD;
          -  Failure to give informed consent from family members.&#xD;
&#xD;
          -  Patient enrolled in other clinical trials&#xD;
&#xD;
          -  Patients with Hepatorenal Syndrome, post renal obstructive AKI, AKI suspected due to&#xD;
             glomerulonephritis, interstitial nephritis or vasculitis based on clinical history and&#xD;
             urine analysis&#xD;
&#xD;
          -  Patients who have already been on hemodialysis before their arrival in the intensive&#xD;
             care unit&#xD;
&#xD;
          -  Patients with severe vasodilatation SVR &lt;400 dyn·s/cm5 and/or lactate &gt; 5 mmol/L&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Dr Rakhi Maiwall, DM</last_name>
    <phone>01146300000</phone>
    <email>rakhi_2011@yahoo.co.in</email>
  </overall_contact>
  <location>
    <facility>
      <name>Institute of Liver &amp; Biliary Sciences</name>
      <address>
        <city>New Delhi</city>
        <state>Delhi</state>
        <zip>110070</zip>
        <country>India</country>
      </address>
    </facility>
    <contact>
      <last_name>Dr Rakhi Maiwall, DM</last_name>
      <phone>01146300000</phone>
      <email>rakhi_2011@yahoo.co.in</email>
    </contact>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>July 28, 2020</last_update_submitted>
  <last_update_submitted_qc>July 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 31, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Acute Kidney Injury</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04494542
org study id: ILBS-Cirrhosis-36
nct id: NCT04494542
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Development of intradialytic hypotension i.e. decrease in defined as a decrease in systolic blood pressure by ≥20 mm Hg or a decrease in MAP by 10 mm Hg after initiation of dialysis
time frame: at 6 hours after dialysis initiation
measure: Mortality in both groups
time frame: Day 28
measure: Duration of mechanical ventilation and ICU stay
time frame: Day 28
measure: AKI recovery at day 14
time frame: Day 14
measure: Renal failure related death at day 7
time frame: Day 7
measure: Lactate clearance at 12 in both groups
time frame: 12 hours
measure: Lactate clearance at 24 hours in both groups
time frame: 24 hours
measure: Reversal of shock at 48 hours
time frame: 48 hours
arm group label: Sustained Low Efficiency Dialysis
arm group type: Experimental
description: Sustained Low Efficiency Dialysis
arm group label: Continuous Renal Replacement Therapy
arm group type: Active Comparator
description: continuous renal replacement therapy
intervention type: Procedure
intervention name: Sustained Low Efficiency Dialysis (SLED)
description: sustained low efficiency dialysis (SLED)
arm group label: Sustained Low Efficiency Dialysis
intervention type: Procedure
intervention name: Continuous Renal Replacement Therapy
description: Continuous Renal Replacement Therapy
arm group label: Continuous Renal Replacement Therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Dr Rakhi Maiwall, DM
phone: 01146300000
email: rakhi_2011@yahoo.co.in
facility: 
contact: 
country: India
responsible party type: Sponsor
mesh term: Liver Cirrhosis
mesh term: Acute Kidney Injury
sharing ipd: Undecided