<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/NCT03277677</url>
  </required_header>
  <id_info>
    <org_study_id>IRB.113/60</org_study_id>
    <nct_id>NCT03277677</nct_id>
  </id_info>
  <brief_title>The Effect of Fluid Resuscitation With 0.9% Sodium Chloride Versus Balanced Crystalloid Solution on Renal Function of Sepsis Patients</brief_title>
  <official_title>The Effect of Fluid Resuscitation With 0.9% Sodium Chloride Versus Balanced Crystalloid Solution on Renal Function of Sepsis Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chulalongkorn University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chulalongkorn University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The high chloride content of 0.9%sodium chloride (0.9%NaCl) leads to adverse&#xD;
      pathophysiological effects in both animals and healthy human volunteers. Small randomized&#xD;
      trials confirm that the hyperchloremic acidosis induced by 0.9%NaCl also occurs in patients.&#xD;
      A strong signal is emerging from recent large propensity-matched and cohort studies for the&#xD;
      adverse effects that 0.9% NaCl has on the clinical outcome in surgical and critically ill&#xD;
      patients when compared with balanced crystalloids. Major complications are the increased&#xD;
      incidences of acute kidney injury and the need for renal replacement therapy, and that&#xD;
      pathological hyperchloremia may increase postoperative mortality.&#xD;
&#xD;
      Fluid resuscitation with 0.9% NaCl in animals with sepsis resulted in hyperchloremic&#xD;
      metabolic acidosis, worsened AKI, and increased mortality when compared with resuscitation&#xD;
      with a balanced crystalloid solution.&#xD;
&#xD;
      Furthermore, hyperchloremic acidosis also resulted in increased concentrations of circulating&#xD;
      inflammatory mediators in an experimental model of severe sepsis in rats, with a&#xD;
      dose-dependent increase in circulating interleukin-6, tumor necrosis factor-a, and&#xD;
      interleukin-10 concentrations with increasing acidosis.&#xD;
&#xD;
      Thus, in this study, investigators compared the effects of a balanced crystalloid solution&#xD;
      with 0.9% NaCl on the renal function in severe sepsis/septic shock patients. Investigators&#xD;
      hypothesized that balanced crystalloid solution resuscitation would decrease AKI incidence&#xD;
      and severity and would improve immunomodulatory effect when compared with 0.9% NaCl&#xD;
      resuscitation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Actual">March 1, 2021</completion_date>
  <primary_completion_date type="Actual">July 1, 2018</primary_completion_date>
  <phase>Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The incidence of acute kidney injury for any stage and severity</measure>
    <time_frame>at day 7</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The neutrophil function (chemotaxis, CD11b ) between two randomized groups at</measure>
    <time_frame>0, 24, and 72 hours after resuscitation.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The monocyte function (HLA-DR) between two randomized groupsafter resuscitation.</measure>
    <time_frame>at 0, 24, and 72 hours after resuscitation.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The inflammatory marker (IL-6, IL-10) between two randomized groups at</measure>
    <time_frame>0, 24, and 72 hours after resuscitation.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urinary neutrophil gelatinase-associated lipocalin (NGAL) after randomization and after resuscitation with trial fluid</measure>
    <time_frame>at 0,24 and 72 hours after resuscitation.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urinary liver-type fatty acid binding protein (L-FABP)</measure>
    <time_frame>at 0,24 and 72 hours after resuscitation.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sequential [Sepsis-related] Organ Failure Assessment (SOFA) Score. (excluding Glasgow Coma Score) at 72 hours after randomization.</measure>
    <time_frame>at 72 hours after randomization.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need of renal replacement therapy within 72 hours after randomization</measure>
    <time_frame>within 72 hours after randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days alive without renal replacement therapy</measure>
    <time_frame>in 28 days after randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay for survivors sanctioned</measure>
    <time_frame>at 28 days after randomization</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">116</enrollment>
  <condition>Sepsis</condition>
  <condition>Septic Shock</condition>
  <condition>Acute Kidney Injury</condition>
  <arm_group>
    <arm_group_label>normal saline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>balanced solution</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal saline</intervention_name>
    <description>for resuscitation in sepsis patients</description>
    <arm_group_label>normal saline</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ringer's Acetate</intervention_name>
    <description>for resuscitation in sepsis patients</description>
    <arm_group_label>balanced solution</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years old&#xD;
&#xD;
          -  Who need fluid resuscitation in the Emergency Room (ER).&#xD;
&#xD;
          -  Who have fulfilled the criteria for sepsis/septic shock within the previous 24 hours&#xD;
             according to sepsis is defined as life-threatening organ dysfunction caused by a&#xD;
             dysregulated host response to infection.&#xD;
&#xD;
             o Patients with infection and resulted from a host's systemic inflammatory response&#xD;
             syndrome (SIRS) to infection are defined as sepsis if meet the criteria 2 or more of&#xD;
&#xD;
               -  Temperature &gt;38°C or &lt;36°C&#xD;
&#xD;
               -  Heart rate &gt;90/min&#xD;
&#xD;
               -  Respiratory rate &gt;20/min or PaCo2 &lt;32 mm Hg (4.3 kPa)&#xD;
&#xD;
               -  White blood cell count &gt;12000/mm3 or &lt;4000/mm3 or &gt;10% immature bands.&#xD;
&#xD;
          -  Patient who have Septic shock is a subset of sepsis in which underlying circulatory&#xD;
             and cellular/metabolic abnormalities are profound enough to substantially increase&#xD;
             mortality.&#xD;
&#xD;
             o Patients with septic shock can be identified with a clinical construct of sepsis&#xD;
             with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and&#xD;
             having a serum lactate level &gt;2 mmol/L (18 mg/dL) despite adequate volume&#xD;
             resuscitation.&#xD;
&#xD;
          -  AND where informed consent is obtainable either from the patient or by proxy (first&#xD;
             degree relative, spouse) if patients aren't in fully conscious status (eg.comatose,&#xD;
             drowsiness, irritable).&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with chronic kidney disease (CKD) defined by baseline serum creatinine &gt; 2.0&#xD;
             in male and 1.5 in female.&#xD;
&#xD;
          -  Patients with End stage renal disease (ESRD) with or without renal replacement&#xD;
             therapy.&#xD;
&#xD;
          -  Patients with active cardiac disease : severe valvular heart, cardiomyopathy,&#xD;
             decompensated heart failure NYHA II-IV, severe pulmonary hypertension.&#xD;
&#xD;
          -  HIV/AIDs Patients.&#xD;
&#xD;
          -  Allergy towards 0.9% NaCl or Ringer's Acetate.&#xD;
&#xD;
          -  Any form of renal replacement therapy.&#xD;
&#xD;
          -  Intracranial bleeding within current hospitalization.&#xD;
&#xD;
          -  Therapy with corticosteroid or non steroidal anti-inflammatory substance.&#xD;
&#xD;
          -  Patients who predicted not to survive more than 24 hours.&#xD;
&#xD;
          -  Pregnant and lactating patients.&#xD;
&#xD;
          -  Withdrawal of active therapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Chulalongkorn university</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <last_update_submitted>March 5, 2021</last_update_submitted>
  <last_update_submitted_qc>March 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chulalongkorn University</investigator_affiliation>
    <investigator_full_name>Nattachai Srisawat ,M.D.</investigator_full_name>
    <investigator_title>Associated professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
    <mesh_term>Acute Kidney Injury</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03277677
org study id: IRB.113/60
nct id: NCT03277677
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The high chloride content of 0.9%sodium chloride (0.9%NaCl) leads to adverse
      pathophysiological effects in both animals and healthy human volunteers. Small randomized
      trials confirm that the hyperchloremic acidosis induced by 0.9%NaCl also occurs in patients.
      A strong signal is emerging from recent large propensity-matched and cohort studies for the
      adverse effects that 0.9% NaCl has on the clinical outcome in surgical and critically ill
      patients when compared with balanced crystalloids. Major complications are the increased
      incidences of acute kidney injury and the need for renal replacement therapy, and that
      pathological hyperchloremia may increase postoperative mortality.

      Fluid resuscitation with 0.9% NaCl in animals with sepsis resulted in hyperchloremic
      metabolic acidosis, worsened AKI, and increased mortality when compared with resuscitation
      with a balanced crystalloid solution.

      Furthermore, hyperchloremic acidosis also resulted in increased concentrations of circulating
      inflammatory mediators in an experimental model of severe sepsis in rats, with a
      dose-dependent increase in circulating interleukin-6, tumor necrosis factor-a, and
      interleukin-10 concentrations with increasing acidosis.

      Thus, in this study, investigators compared the effects of a balanced crystalloid solution
      with 0.9% NaCl on the renal function in severe sepsis/septic shock patients. Investigators
      hypothesized that balanced crystalloid solution resuscitation would decrease AKI incidence
      and severity and would improve immunomodulatory effect when compared with 0.9% NaCl
      resuscitation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The incidence of acute kidney injury for any stage and severity
time frame: at day 7
measure: The neutrophil function (chemotaxis, CD11b ) between two randomized groups at
time frame: 0, 24, and 72 hours after resuscitation.
measure: The monocyte function (HLA-DR) between two randomized groupsafter resuscitation.
time frame: at 0, 24, and 72 hours after resuscitation.
measure: The inflammatory marker (IL-6, IL-10) between two randomized groups at
time frame: 0, 24, and 72 hours after resuscitation.
measure: Urinary neutrophil gelatinase-associated lipocalin (NGAL) after randomization and after resuscitation with trial fluid
time frame: at 0,24 and 72 hours after resuscitation.
measure: Urinary liver-type fatty acid binding protein (L-FABP)
time frame: at 0,24 and 72 hours after resuscitation.
measure: Sequential [Sepsis-related] Organ Failure Assessment (SOFA) Score. (excluding Glasgow Coma Score) at 72 hours after randomization.
time frame: at 72 hours after randomization.
measure: Need of renal replacement therapy within 72 hours after randomization
time frame: within 72 hours after randomization
measure: Days alive without renal replacement therapy
time frame: in 28 days after randomization
measure: Hospital length of stay for survivors sanctioned
time frame: at 28 days after randomization
arm group label: normal saline
arm group type: Active Comparator
arm group label: balanced solution
arm group type: Active Comparator
intervention type: Drug
intervention name: Normal saline
description: for resuscitation in sepsis patients
arm group label: normal saline
intervention type: Drug
intervention name: Ringer's Acetate
description: for resuscitation in sepsis patients
arm group label: balanced solution
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
facility: 
country: Thailand
responsible party type: Principal Investigator
investigator affiliation: Chulalongkorn University
investigator full name: Nattachai Srisawat ,M.D.
investigator title: Associated professor
mesh term: Sepsis
mesh term: Toxemia
mesh term: Acute Kidney Injury
sharing ipd: No