<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/NCT03256461</url>
  </required_header>
  <id_info>
    <org_study_id>LCGRIS-01</org_study_id>
    <nct_id>NCT03256461</nct_id>
  </id_info>
  <brief_title>Lactate Clearance Goal-directed Therapy in Sepsis</brief_title>
  <official_title>Multi-center Clinical Trial of Lactate Clearance Goal-directed Fluid Resuscitation in Patients With Sepsis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nanfang Hospital, Southern Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nanfang Hospital, Southern Medical 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Serum lactate level is depended on the balance between lactate production and clearance. It&#xD;
      is seen as a sensitive indicator reflecting not only the low systemic perfusion but&#xD;
      microcirculatory dysfunction which cause global or regional tissue hypoxia (as a result of&#xD;
      impaired mitochondrial oxidation). 2016 Surviving Sepsis Campaign guideline stated &quot;We&#xD;
      suggest guiding resuscitation to normalize lactate in patients with elevated lactate levels&#xD;
      as a marker of tissue hypoperfusion&quot;, with weak recommendation and low quality of evidence.&#xD;
      Several trials which evaluated the resuscitation strategy included lactate clearance as a&#xD;
      target while based on 2.0 diagnostic criteria for sepsis, finally showed conflicting results.&#xD;
      The aim of this study is to explore the feasibility of lactate clearance guide resuscitation&#xD;
      in sepsis that defined by The Third International Consensus Definitions for Sepsis and Septic&#xD;
      shock through multi-center, central-randomization clinical trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sepsis remains a great challenge for clinicians, early goal-directed therapy(EGDT), referring&#xD;
      to a number of target-achieving indicators including systemic central venous oxygen&#xD;
      saturation(ScvO2) after initial fluid resuscitation within 6 hours, has been one of the main&#xD;
      treatment for sepsis. ScvO2 is the only indicator that reflects tissue oxygen metabolism.&#xD;
      However, there're studies confirmed that ScvO2 oriented EGDT cannot reduce the mortality of&#xD;
      sepsis. So it is important to find out a more effective indicator. Lactic acid is a product&#xD;
      of anaerobic metabolism of the body, lactate clearance has been found to effectively predict&#xD;
      the prognosis of sepsis. Few studies have shown that lactate clearance oriented fluid&#xD;
      resuscitation can be of benefit in patients with sepsis. Nevertheless, whether lactate&#xD;
      clearance could be combined with sepsis Bundle as a new marker to improve the prognosis&#xD;
      remains a problem. The objective of this study is to discuss the feasibility of lactate&#xD;
      clearance oriented sepsis treatment through multi-center clinical trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">August 21, 2017</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 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>
    <intervention_model_description>This trial is a prospective, multicenter, single-blind, parallel-group, central-randomized, controlled trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>28-d mortality</measure>
    <time_frame>Four years</time_frame>
    <description>All-cause mortality at 28 days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ICU Length of stay</measure>
    <time_frame>Four years</time_frame>
    <description>Length of stay in the intensive care unit (ICU)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Length of stay</measure>
    <time_frame>Four years</time_frame>
    <description>Length of stay in hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>90-d mortality</measure>
    <time_frame>Four years</time_frame>
    <description>All-cause mortality at 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In-hospital mortality</measure>
    <time_frame>Four years</time_frame>
    <description>All-cause mortality during hospitalization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In-ICU mortality</measure>
    <time_frame>Four years</time_frame>
    <description>All-cause mortality during ICU stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Administered treatments</measure>
    <time_frame>Four years</time_frame>
    <description>Administered treatments included: crystalloid volume, vasopressor administered, dobutamine, red blood cell(RBC) transfusion, mechanical ventilation, renal-replacement therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SOFA at 24h</measure>
    <time_frame>Four years</time_frame>
    <description>Sequential Organ Failure Assessment(SOFA) at 24 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Four years</time_frame>
    <description>Proportion of patients reporting treatment-emergent adverse events</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">1128</enrollment>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>Lactate clearance 10% target group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lactate clearance falls by 10-percent every two hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lactate clearance 20% target group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lactate clearance falls by 20-percent every two hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard EGDT group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Refer to the Surviving Sepsis Campaign(SSC) 2012 sepsis guidelines within 6 h liquid resuscitation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Lactate clearance 10% target group</intervention_name>
    <description>Participants receive the protocolized resuscitation to achieve the goal of 10-percent lactate clearance every two hours within the initial six hours of treatment.</description>
    <arm_group_label>Lactate clearance 10% target group</arm_group_label>
    <other_name>Lac% 10% group</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Lactate clearance 20% target group</intervention_name>
    <description>Participants receive the protocolized resuscitation to achieve the goal of 20-percent lactate clearance every two hours within the initial six hours of treatment.</description>
    <arm_group_label>Lactate clearance 20% target group</arm_group_label>
    <other_name>Lac% 20% group</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Standard EGDT group</intervention_name>
    <description>Participants receive the strategy of early goal-directed treatment of sepsis fluid resuscitation.</description>
    <arm_group_label>Standard EGDT group</arm_group_label>
    <other_name>EGDT group</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Older than 17 years old.&#xD;
&#xD;
          -  Primary diagnosis is sepsis, means being confirmed or suspected infection while have&#xD;
             at least 2 points of quickSOFA(qSOFA).&#xD;
&#xD;
          -  Be transferred to intensive care unit (ICU) for the first time during this&#xD;
             hospitalization.&#xD;
&#xD;
          -  Elevated lactate ≥3.0mmol/L.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute hemorrhage uncontrolled.&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Known liver disease - Child-Pugh classes C, acute hepatic failure, severe hepatopathy&#xD;
             accompany with prominent portal hypertension.&#xD;
&#xD;
          -  Known being in an immunosuppressive state:&#xD;
&#xD;
               1. Suffering from any disease that is unrelated with sepsis that severely inhibits&#xD;
                  the immune to infection, such as: active hematological or lymphoma malignancy, or&#xD;
                  during immunosuppressive therapy, such as chemotherapy or radiotherapy.&#xD;
&#xD;
               2. Known human immunodeficiency virus (HIV) serology positive.&#xD;
&#xD;
          -  Known chronic kidney disease.&#xD;
&#xD;
          -  Suffering from any disease that affects lactate kinetics, such as mitochondrial&#xD;
             encephalopathy, congenital hyperlipidemia, Wernicke encephalopathy, etc. Or other&#xD;
             probable cause of hyperlactatemia.&#xD;
&#xD;
          -  Took any drugs that affect lactate kinetics within the effective time window, such as&#xD;
             taking metformin or phenylephrine within 1 week.&#xD;
&#xD;
          -  Suffering from any disease that restricts resuscitation, such as heart failure,&#xD;
             cardiac surgery, severe heart disease etc, or suffered from a cardio-pulmonary&#xD;
             resuscitation,.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chen Zhongqing, Ph.D</last_name>
    <role>Study Chair</role>
    <affiliation>Southern Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chen Zhongqing, Ph.D</last_name>
    <phone>020-61641886</phone>
    <email>13503049103@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>NanFang hospital</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510515</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhongqing Chen, Ph.D</last_name>
      <phone>+86 20 6164 1886</phone>
      <email>13503049103@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Yaoyuan Zhang, Master</last_name>
      <email>m18620660446@163.com</email>
    </contact_backup>
    <investigator>
      <last_name>Weijun Fu, Master</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Xingui Dai, Master</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yaoyuan Zhang, Master</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>August 21, 2017</last_update_submitted>
  <last_update_submitted_qc>August 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sepsis</keyword>
  <keyword>lactate clearance</keyword>
  <keyword>protocolized resuscitation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/61/NCT03256461/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/61/NCT03256461/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03256461
org study id: LCGRIS-01
nct id: NCT03256461
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Serum lactate level is depended on the balance between lactate production and clearance. It
      is seen as a sensitive indicator reflecting not only the low systemic perfusion but
      microcirculatory dysfunction which cause global or regional tissue hypoxia (as a result of
      impaired mitochondrial oxidation). 2016 Surviving Sepsis Campaign guideline stated "We
      suggest guiding resuscitation to normalize lactate in patients with elevated lactate levels
      as a marker of tissue hypoperfusion", with weak recommendation and low quality of evidence.
      Several trials which evaluated the resuscitation strategy included lactate clearance as a
      target while based on 2.0 diagnostic criteria for sepsis, finally showed conflicting results.
      The aim of this study is to explore the feasibility of lactate clearance guide resuscitation
      in sepsis that defined by The Third International Consensus Definitions for Sepsis and Septic
      shock through multi-center, central-randomization clinical trial.
Sepsis remains a great challenge for clinicians, early goal-directed therapy(EGDT), referring
      to a number of target-achieving indicators including systemic central venous oxygen
      saturation(ScvO2) after initial fluid resuscitation within 6 hours, has been one of the main
      treatment for sepsis. ScvO2 is the only indicator that reflects tissue oxygen metabolism.
      However, there're studies confirmed that ScvO2 oriented EGDT cannot reduce the mortality of
      sepsis. So it is important to find out a more effective indicator. Lactic acid is a product
      of anaerobic metabolism of the body, lactate clearance has been found to effectively predict
      the prognosis of sepsis. Few studies have shown that lactate clearance oriented fluid
      resuscitation can be of benefit in patients with sepsis. Nevertheless, whether lactate
      clearance could be combined with sepsis Bundle as a new marker to improve the prognosis
      remains a problem. The objective of this study is to discuss the feasibility of lactate
      clearance oriented sepsis treatment through multi-center clinical trial.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This trial is a prospective, multicenter, single-blind, parallel-group, central-randomized, controlled trial
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: 28-d mortality
time frame: Four years
description: All-cause mortality at 28 days
measure: ICU Length of stay
time frame: Four years
description: Length of stay in the intensive care unit (ICU)
measure: Hospital Length of stay
time frame: Four years
description: Length of stay in hospital
measure: 90-d mortality
time frame: Four years
description: All-cause mortality at 90 days
measure: In-hospital mortality
time frame: Four years
description: All-cause mortality during hospitalization
measure: In-ICU mortality
time frame: Four years
description: All-cause mortality during ICU stay
measure: Administered treatments
time frame: Four years
description: Administered treatments included: crystalloid volume, vasopressor administered, dobutamine, red blood cell(RBC) transfusion, mechanical ventilation, renal-replacement therapy
measure: SOFA at 24h
time frame: Four years
description: Sequential Organ Failure Assessment(SOFA) at 24 hours
measure: Adverse events
time frame: Four years
description: Proportion of patients reporting treatment-emergent adverse events
arm group label: Lactate clearance 10% target group
arm group type: Experimental
description: Lactate clearance falls by 10-percent every two hours.
arm group label: Lactate clearance 20% target group
arm group type: Experimental
description: Lactate clearance falls by 20-percent every two hours.
arm group label: Standard EGDT group
arm group type: Placebo Comparator
description: Refer to the Surviving Sepsis Campaign(SSC) 2012 sepsis guidelines within 6 h liquid resuscitation.
intervention type: Behavioral
intervention name: Lactate clearance 10% target group
description: Participants receive the protocolized resuscitation to achieve the goal of 10-percent lactate clearance every two hours within the initial six hours of treatment.
arm group label: Lactate clearance 10% target group
other name: Lac% 10% group
intervention type: Behavioral
intervention name: Lactate clearance 20% target group
description: Participants receive the protocolized resuscitation to achieve the goal of 20-percent lactate clearance every two hours within the initial six hours of treatment.
arm group label: Lactate clearance 20% target group
other name: Lac% 20% group
intervention type: Behavioral
intervention name: Standard EGDT group
description: Participants receive the strategy of early goal-directed treatment of sepsis fluid resuscitation.
arm group label: Standard EGDT group
other name: EGDT group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Chen Zhongqing, Ph.D
role: Study Chair
affiliation: Southern Medical University
last name: Chen Zhongqing, Ph.D
phone: 020-61641886
email: 13503049103@163.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
country: China
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Toxemia
sharing ipd: No
provided document: 
provided document: 