<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/NCT03038503</url>
  </required_header>
  <id_info>
    <org_study_id>ID 09-59-14</org_study_id>
    <nct_id>NCT03038503</nct_id>
  </id_info>
  <brief_title>What Should be the Next Vasopressor for Severe Septic Shock? Methylene Blue or Terlipressin</brief_title>
  <official_title>What Should be the Next Vasopressor for Severe Septic Shock Patients? Methylene Blue or Terlipressin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ramathibodi Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ramathibodi Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The ICU mortality rate of patients with septic shock was still high upto 54.1%.In first 6&#xD;
      hours of resuscitation, the goals of resuscitation in sepsis shock after adequate fluid&#xD;
      resuscitation is MAP ≥65 mmHg. In refractory septic shock patient, prolong shock correlate&#xD;
      with poor outcome due to multiple organ failure. Alternative vasopressor in septic shock with&#xD;
      catecholamine resistance has been studied such as terlipressin, methylene blue&#xD;
&#xD;
        -  Terlipressin (TP) mediate vasoconstriction via V1 receptors coupled to phospholipase C,&#xD;
           and increases intracellular Ca2+ concentration&#xD;
&#xD;
        -  Methylene blue (MB) directly inhibits nitric oxide synthase (NOS) by inhibit the enzyme&#xD;
           guanylate cyclase (GC)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>mortality rate</measure>
    <time_frame>7 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>time to wean of vasopressor</measure>
    <time_frame>through complete weaning off vasopressor, an average of 24 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>ICU duration</measure>
    <time_frame>through out off indication need ICU care, an average of 7 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>hemodynamic parameter: Mean arterial pressure (mmHg)</measure>
    <time_frame>every 30 min after start protocol up to 6 hr then every 1 hr up to 24 hours</time_frame>
    <description>mmHg, A-line monitoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>hemodynamic parameter: lactate (mmol/l)</measure>
    <time_frame>every 2 hr until 6 hr then every 4 hr until wean off vasopressor up to 24 hours</time_frame>
    <description>mmol/l</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>hemodynamic parameter: urine output (ml)</measure>
    <time_frame>every 2 hr until wean off vasopressor up to 24 hours</time_frame>
    <description>ml</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Septic Shock</condition>
  <condition>Refractory Shock</condition>
  <arm_group>
    <arm_group_label>A</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>standard care septic shock according sepsis bundles</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>after defined refractory shock (adequate fluid resuscitation + add NE&gt;0.5 mcg/kg/min) add Methylene blue 1 mg/kg iv drip then 2 hr later drip 0.5 mg/kg/hr*4 hr (intervention add on to standard care)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>after defined refractory shock (adequate fluid resuscitation + add NE&gt;0.5 mcg/kg/min) add terlipressin 1 mg IV then repeated dose 20 min later if unstable BP (intervention add on to standard care)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylene Blue</intervention_name>
    <description>after defined refractory shock (need NE&gt;0.5 mcg/kg/min) add Methylene blue 1 mg/kg iv drip then 2 hr later drip 0.5 mg/kg/hr*4 hr (intervention add on to standard care)</description>
    <arm_group_label>B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Terlipressin</intervention_name>
    <description>after defined refractory shock (need NE&gt;0.5 mcg/kg/min) add terlipressin 1 mg IV then repeated dose 20 min later if unstable BP (intervention add on to standard care)</description>
    <arm_group_label>C</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;15 years old&#xD;
&#xD;
          -  Diagnosis septic shock as SCCM/ACCP&#xD;
&#xD;
          -  Refractory septic shock defined as hypotension although adequate fluid resuscitate and&#xD;
             high dose vasopressor(NE &gt;0.5 mcg/kg/min)&#xD;
&#xD;
          -  Concent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known case G6PD deficiency&#xD;
&#xD;
          -  Acute respiratory distress syndrome (ARDS)&#xD;
&#xD;
          -  Hx of drug allergy MB, NE, terlipressin&#xD;
&#xD;
          -  Hx of Raynaud's phenomenon, systemic sclerosis, PHT&#xD;
&#xD;
          -  Known case coronary heart disease without treatment&#xD;
&#xD;
          -  Current drug use serotonin reuptake inhibitors (SSRI), Serotonin and norepinephrine&#xD;
             reuptake inhibitors (SNRIs)&#xD;
&#xD;
          -  Reject to join project&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>viratch tangsujaritvijit, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Mahidol University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>munthana sundusadee, MD</last_name>
    <phone>66639010178</phone>
    <email>opal_janeway@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Ramathibodi hospital</name>
      <address>
        <city>Bangkok</city>
        <zip>066</zip>
        <country>Thailand</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>munthana sundusadee, md</last_name>
      <phone>66639010178</phone>
      <email>opal_janeway@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>December 22, 2016</study_first_submitted>
  <study_first_submitted_qc>January 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>August 28, 2018</last_update_submitted>
  <last_update_submitted_qc>August 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ramathibodi Hospital</investigator_affiliation>
    <investigator_full_name>munthana sundusadee</investigator_full_name>
    <investigator_title>fellowship in department of pulmonary and critical care department</investigator_title>
  </responsible_party>
  <keyword>refractory septic shock</keyword>
  <keyword>catecholamine resistance septic shock</keyword>
  <keyword>terlipressin</keyword>
  <keyword>methylene blue</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>Terlipressin</mesh_term>
    <mesh_term>Methylene Blue</mesh_term>
  </intervention_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/NCT03038503
org study id: ID 09-59-14
nct id: NCT03038503
lead sponsor: 
has dmc: No
The ICU mortality rate of patients with septic shock was still high upto 54.1%.In first 6
      hours of resuscitation, the goals of resuscitation in sepsis shock after adequate fluid
      resuscitation is MAP ≥65 mmHg. In refractory septic shock patient, prolong shock correlate
      with poor outcome due to multiple organ failure. Alternative vasopressor in septic shock with
      catecholamine resistance has been studied such as terlipressin, methylene blue

        -  Terlipressin (TP) mediate vasoconstriction via V1 receptors coupled to phospholipase C,
           and increases intracellular Ca2+ concentration

        -  Methylene blue (MB) directly inhibits nitric oxide synthase (NOS) by inhibit the enzyme
           guanylate cyclase (GC)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: mortality rate
time frame: 7 days
measure: time to wean of vasopressor
time frame: through complete weaning off vasopressor, an average of 24 hours
measure: ICU duration
time frame: through out off indication need ICU care, an average of 7 days
measure: hemodynamic parameter: Mean arterial pressure (mmHg)
time frame: every 30 min after start protocol up to 6 hr then every 1 hr up to 24 hours
description: mmHg, A-line monitoring
measure: hemodynamic parameter: lactate (mmol/l)
time frame: every 2 hr until 6 hr then every 4 hr until wean off vasopressor up to 24 hours
description: mmol/l
measure: hemodynamic parameter: urine output (ml)
time frame: every 2 hr until wean off vasopressor up to 24 hours
description: ml
arm group label: A
arm group type: No Intervention
description: standard care septic shock according sepsis bundles
arm group label: B
arm group type: Experimental
description: after defined refractory shock (adequate fluid resuscitation + add NE>0.5 mcg/kg/min) add Methylene blue 1 mg/kg iv drip then 2 hr later drip 0.5 mg/kg/hr*4 hr (intervention add on to standard care)
arm group label: C
arm group type: Experimental
description: after defined refractory shock (adequate fluid resuscitation + add NE>0.5 mcg/kg/min) add terlipressin 1 mg IV then repeated dose 20 min later if unstable BP (intervention add on to standard care)
intervention type: Drug
intervention name: Methylene Blue
description: after defined refractory shock (need NE>0.5 mcg/kg/min) add Methylene blue 1 mg/kg iv drip then 2 hr later drip 0.5 mg/kg/hr*4 hr (intervention add on to standard care)
arm group label: B
intervention type: Drug
intervention name: Terlipressin
description: after defined refractory shock (need NE>0.5 mcg/kg/min) add terlipressin 1 mg IV then repeated dose 20 min later if unstable BP (intervention add on to standard care)
arm group label: C
criteria: 
gender: All
minimum age: 15 Years
maximum age: N/A
healthy volunteers: No
last name: viratch tangsujaritvijit, MD
role: Study Chair
affiliation: Mahidol University
last name: munthana sundusadee, MD
phone: 66639010178
email: opal_janeway@hotmail.com
facility: 
status: Recruiting
contact: 
country: Thailand
responsible party type: Principal Investigator
investigator affiliation: Ramathibodi Hospital
investigator full name: munthana sundusadee
investigator title: fellowship in department of pulmonary and critical care department
mesh term: Shock, Septic
mesh term: Shock
mesh term: Terlipressin
mesh term: Methylene Blue
sharing ipd: No