<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/NCT04449757</url>
  </required_header>
  <id_info>
    <org_study_id>2020044</org_study_id>
    <nct_id>NCT04449757</nct_id>
  </id_info>
  <brief_title>Bicarbonated Ringer's Solution Versus Lactated Ringer's Solution in Patients With Septic Shock</brief_title>
  <official_title>Fluid Resuscitation Management for Patients With Septic Shock: the Efficacy and Safety Comparison Between Bicarbonated Ringer's Solution and Lactated Ringer's Solution</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhongnan Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zhongnan Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this prospective randomized controlled trial, investigators aim to study the effects and&#xD;
      safety of bicarbonated Ringer's solution in patients with septic shock compared with lactated&#xD;
      ringer's solution, and provide evidence for current fluid resuscitation strategies for septic&#xD;
      shock.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Although the latest guidelines recommend crystalloids as the first choice for the patients'&#xD;
      fluid resuscitation, it still remains controversial that which crystalloid solution is the&#xD;
      best choice. It is reported that balanced crystalloid can result in better outcomes than&#xD;
      saline for critically ill patients. However, there are few studies conducted between&#xD;
      different crystalloid solutions.&#xD;
&#xD;
      Lactated ringer's solution is the longest-used crystalloid solution. Compared with lactated&#xD;
      ringer's solution whose anion is lactate, the anion of bicarbonate ringer's solution is&#xD;
      bicarbonate. And lactate needs to be metabolized into bicarbonate through the mitochondria of&#xD;
      the liver before it can play an alkalization role. Therefore, in theory, bicarbonate ringer's&#xD;
      solution does not need to rely on liver metabolism, the onset time to maintain acid-base&#xD;
      balance is shorter, and it may be more suitable for patients with severe acidosis. In&#xD;
      patients with septic shock, the incidence of moderate to severe metabolic is increased.&#xD;
      Bicarbonate ringer's solution can directly supplement the concentration of bicarbonate, while&#xD;
      lactated ringer's solution needs to take time and be metabolized in the liver. Thus, we&#xD;
      hypothesize that bicarbonate ringer's solution is more effective for patients with shock and&#xD;
      metabolic acidosis than lactated ringer's solution.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 1, 2020</start_date>
  <completion_date type="Anticipated">May 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">May 30, 2021</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>the average doses of vasopressors</measure>
    <time_frame>From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate &lt;2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.</time_frame>
    <description>total doses of norepinephrine÷weight÷duration of usage</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>the PH value</measure>
    <time_frame>0, 3 hours, 6 hours, 12 hours, 24 hours</time_frame>
    <description>the potencial of hydrogen of arterial blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the BE value</measure>
    <time_frame>0, 3 hours, 6 hours, 12 hours, 24 hours</time_frame>
    <description>the base excess of arterial blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>shock reversal time</measure>
    <time_frame>From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate &lt;2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.</time_frame>
    <description>From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate &lt;2.2mmol/l, or discontinuation of vasoactive drugs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>total volume of fluids before hemodynamic stabilization</measure>
    <time_frame>From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate &lt;2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.</time_frame>
    <description>total volume of bicarbonated ringers/lactated ringers before hemodynamic stabilization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the change of serum lactate value at the 6th hour</measure>
    <time_frame>6 hours</time_frame>
    <description>serum lactate (6h) - serum lactate (0h)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the proportion of patients whose serum lactate decreases 30%</measure>
    <time_frame>From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate &lt;2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.</time_frame>
    <description>the proportion of patients whose serum lactate decreases 30%</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>mortality from any cause</measure>
    <time_frame>on the day28 after enrollment</time_frame>
    <description>the rate of death from any cause within 28 days after enrollment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the rate of metabolic alkalosis</measure>
    <time_frame>From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate &lt;2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.</time_frame>
    <description>the percentage of metabolic alkalosis (PH&gt;7.45 and HCO3&gt;26mmol/L)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">260</enrollment>
  <condition>Septic Shock</condition>
  <condition>Fluid Resuscitation</condition>
  <condition>Crystalloid Solution</condition>
  <condition>Intensive Care Unit</condition>
  <arm_group>
    <arm_group_label>bicarbonated ringer's solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>We apply bicarbonated ringer's solution as resuscitation fluid to patients with septic shock.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>lactated ringer's solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>We apply lactated ringer's solution as resuscitation fluid to patients with septic shock.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bicarbonated Ringer's solution</intervention_name>
    <description>Method of administration: intravenous infusion; 500-1000ml each time; Speed of infusion: it is decided by the clinicians.</description>
    <arm_group_label>bicarbonated ringer's solution</arm_group_label>
    <other_name>Ringers Bicarbonate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lactated Ringer's solution</intervention_name>
    <description>Method of administration: intravenous infusion; 500-1000ml each time; Speed of infusion: it is decided by the clinicians.</description>
    <arm_group_label>lactated ringer's solution</arm_group_label>
    <other_name>Ringers Lactate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. At the age of 18 to 75;&#xD;
&#xD;
          -  2. Being treated in the ICU;&#xD;
&#xD;
          -  3. Diagnosed as septic shock according tho the definition of Sepsis 3.0 with fluid&#xD;
             resuscitation requirement.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Severe hepatic failure;&#xD;
&#xD;
          -  2. Possible brain injury;&#xD;
&#xD;
          -  3. With absolute contraindications for central vena catheterization;&#xD;
&#xD;
          -  4. Ever participated in another clinical trial within 30 days prior enrollment;&#xD;
&#xD;
          -  5. Have corrected metabolic acidosis through alkaline drug application within 24 hours&#xD;
             prior to enrollment;&#xD;
&#xD;
          -  6. Hypermagnesemia or hypothyroidism;&#xD;
&#xD;
          -  7. Pregnant of breast-feeding women;&#xD;
&#xD;
          -  8. Considered inevitable death;&#xD;
&#xD;
          -  9. Other situations where investigators think enrollment is not appropriate.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Zhongnan Hospital of Wuhan University</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 29, 2020</study_first_posted>
  <last_update_submitted>June 23, 2020</last_update_submitted>
  <last_update_submitted_qc>June 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Zhongnan Hospital</investigator_affiliation>
    <investigator_full_name>ZhiYong Peng</investigator_full_name>
    <investigator_title>Professor; Chief physician</investigator_title>
  </responsible_party>
  <keyword>septic shock</keyword>
  <keyword>fluid resuscitation</keyword>
  <keyword>crystalloid solution</keyword>
  <keyword>intensive care unit</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Shock, Septic</mesh_term>
    <mesh_term>Shock</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pharmaceutical Solutions</mesh_term>
  </intervention_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/NCT04449757
org study id: 2020044
nct id: NCT04449757
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
In this prospective randomized controlled trial, investigators aim to study the effects and
      safety of bicarbonated Ringer's solution in patients with septic shock compared with lactated
      ringer's solution, and provide evidence for current fluid resuscitation strategies for septic
      shock.
Although the latest guidelines recommend crystalloids as the first choice for the patients'
      fluid resuscitation, it still remains controversial that which crystalloid solution is the
      best choice. It is reported that balanced crystalloid can result in better outcomes than
      saline for critically ill patients. However, there are few studies conducted between
      different crystalloid solutions.

      Lactated ringer's solution is the longest-used crystalloid solution. Compared with lactated
      ringer's solution whose anion is lactate, the anion of bicarbonate ringer's solution is
      bicarbonate. And lactate needs to be metabolized into bicarbonate through the mitochondria of
      the liver before it can play an alkalization role. Therefore, in theory, bicarbonate ringer's
      solution does not need to rely on liver metabolism, the onset time to maintain acid-base
      balance is shorter, and it may be more suitable for patients with severe acidosis. In
      patients with septic shock, the incidence of moderate to severe metabolic is increased.
      Bicarbonate ringer's solution can directly supplement the concentration of bicarbonate, while
      lactated ringer's solution needs to take time and be metabolized in the liver. Thus, we
      hypothesize that bicarbonate ringer's solution is more effective for patients with shock and
      metabolic acidosis than lactated ringer's solution.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: the average doses of vasopressors
time frame: From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate <2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.
description: total doses of norepinephrine÷weight÷duration of usage
measure: the PH value
time frame: 0, 3 hours, 6 hours, 12 hours, 24 hours
description: the potencial of hydrogen of arterial blood
measure: the BE value
time frame: 0, 3 hours, 6 hours, 12 hours, 24 hours
description: the base excess of arterial blood
measure: shock reversal time
time frame: From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate <2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.
description: From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate <2.2mmol/l, or discontinuation of vasoactive drugs
measure: total volume of fluids before hemodynamic stabilization
time frame: From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate <2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.
description: total volume of bicarbonated ringers/lactated ringers before hemodynamic stabilization
measure: the change of serum lactate value at the 6th hour
time frame: 6 hours
description: serum lactate (6h) - serum lactate (0h)
measure: the proportion of patients whose serum lactate decreases 30%
time frame: From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate <2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.
description: the proportion of patients whose serum lactate decreases 30%
measure: mortality from any cause
time frame: on the day28 after enrollment
description: the rate of death from any cause within 28 days after enrollment
measure: the rate of metabolic alkalosis
time frame: From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate <2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.
description: the percentage of metabolic alkalosis (PH>7.45 and HCO3>26mmol/L)
arm group label: bicarbonated ringer's solution
arm group type: Experimental
description: We apply bicarbonated ringer's solution as resuscitation fluid to patients with septic shock.
arm group label: lactated ringer's solution
arm group type: Experimental
description: We apply lactated ringer's solution as resuscitation fluid to patients with septic shock.
intervention type: Drug
intervention name: Bicarbonated Ringer's solution
description: Method of administration: intravenous infusion; 500-1000ml each time; Speed of infusion: it is decided by the clinicians.
arm group label: bicarbonated ringer's solution
other name: Ringers Bicarbonate
intervention type: Drug
intervention name: Lactated Ringer's solution
description: Method of administration: intravenous infusion; 500-1000ml each time; Speed of infusion: it is decided by the clinicians.
arm group label: lactated ringer's solution
other name: Ringers Lactate
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Zhongnan Hospital
investigator full name: ZhiYong Peng
investigator title: Professor; Chief physician
mesh term: Shock, Septic
mesh term: Shock
mesh term: Pharmaceutical Solutions
sharing ipd: Undecided