xml: <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/NCT06005558</url>
    </required_header>
    <id_info>
      <org_study_id>Methylene blue</org_study_id>
      <nct_id>NCT06005558</nct_id>
    </id_info>
    <brief_title>Low Dose Versus High Dose Methylene Blue in Septic Patients</brief_title>
    <official_title>Comparative Study Between High and Low Dose Methylene Blue Infusion in Septic Cancer Patients. A Randomized Blinded Controlled Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National Cancer Institute, Egypt</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>National Cancer Institute, Egypt</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 main aim of this study is to examine the various effects of continuous methylene blue&#xD;
        infusion in septic cancer patients and to compare it with the traditional infusion of&#xD;
        noradrenaline in such patients .&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Exaggerated host response to infection, may result in sepsis, which is life-threatening organ&#xD;
        dysfunction . Though considered the number one cause of in-hospital deaths , it can be&#xD;
        treatable with early prompt interventions.&#xD;
  &#xD;
        The 2021 SSC Guidelines use the Third International Consensus definitions, also known as&#xD;
        Sepsis-3. Where sepsis is defined as &quot;life-threatening organ dysfunction caused by a&#xD;
        dysregulated host response to infection.&quot; Organ dysfunction is evidenced by an increased&#xD;
        score of 2 or more in the Quick Sequential [Sepsis-related] Organ Failure Assessment (QSOFA),&#xD;
        and septic shock is considered as &quot;a subset of sepsis in which particularly profound&#xD;
        circulatory, cellular, and metabolic abnormalities are associated with a greater risk of&#xD;
        mortality than with sepsis alone.&quot; To diagnose septic shock, an euvolemic patient must&#xD;
        require vasopressor support to achieve a mean arterial pressure of at least 65 mm Hg and have&#xD;
        a lactate level above 2 mmol/L.&#xD;
  &#xD;
        The triad of intravenous fluid, vasopressors and antibiotics in the first hour is the&#xD;
        mainstay of septic shock management. Aim of management is to maintain patient hemodynamically&#xD;
        stable until antibiotics kick in and fight infection. In case of non-responders, low dose&#xD;
        corticosteroids are prescribed. Other drugs need to be studied to also help in cases of&#xD;
        non-responders and to improve outcome in general. Methylene blue (MB) is a nitric oxide&#xD;
        inhibitor that can counteract the vasodilatation in early septic shock.&#xD;
  &#xD;
        Nitric oxide (NO) activates soluble guanylyl cyclase (sGC) which activates cyclic guanosine&#xD;
        monophosphate (cGMP)-dependent protein kinases (PKGs) that cause vasodilatation. Methylene&#xD;
        blue selectively blocks sGC and inhibits iNOS. Therefore, it selectively acts on the&#xD;
        microcirculation.&#xD;
  &#xD;
        Onset of action of intravenous MB is 30-60 min. Peak concentration at 30 min. It is excreted&#xD;
        through bile and fecal routes plus through the kidneys. Due to the short Plasma half-life of&#xD;
        5-6 hours, some studies used continuous infusion of 0.25-2 mg/kg/h, for up to 3 days&#xD;
        following the initial bolus dose&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 1, 2023</start_date>
    <completion_date type="Anticipated">February 15, 2024</completion_date>
    <primary_completion_date type="Anticipated">January 30, 2024</primary_completion_date>
    <phase>Phase 2/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>Double (Participant, Care Provider)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Discontinuation of vasopressor</measure>
      <time_frame>7 days</time_frame>
      <description>Time for noradrenaline discontinuation</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Mortality</measure>
      <time_frame>28 days</time_frame>
      <description>Number of deaths</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">90</enrollment>
    <condition>Septic Shock</condition>
    <arm_group>
      <arm_group_label>Normal saline</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>30 patients will receive placebo of 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of Nacl for 72 hours.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>methylene blue low dose</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>30 patients will receive a bolus of MB 1mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>methylene blue high dose</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>30 patients will receive a bolus of MB 4mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Normal saline</intervention_name>
      <description>100 ml 0.9% Nacl over 20 minutes, followed by continuous infusion of normal saline for 72 hours.</description>
      <arm_group_label>methylene blue high dose</arm_group_label>
      <arm_group_label>methylene blue low dose</arm_group_label>
      <other_name>Control</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Methylene Blue low dose</intervention_name>
      <description>A bolus of MB 1mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.</description>
      <arm_group_label>Normal saline</arm_group_label>
      <arm_group_label>methylene blue high dose</arm_group_label>
      <other_name>Low dose</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Methylene Blue high dose</intervention_name>
      <description>A bolus of MB 4mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.</description>
      <arm_group_label>Normal saline</arm_group_label>
      <arm_group_label>methylene blue low dose</arm_group_label>
      <other_name>High dose</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients aged ≥ 18 years and ≤ 65 with septic shock as defined by Sepsis-3 criteria&#xD;
               (confirmed infection, requiring vasopressor to maintain a mean arterial blood pressure&#xD;
               (MAP) ≥ 65 mmHg, and serum lactate &gt; 2 mmol/L after adequate fluid resuscitation), and&#xD;
               requiring mechanical ventilation.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  myocardial infarction or cerebrovascular accident within the last 3 months.&#xD;
  &#xD;
            -  severe lung , liver or kidney disease (creatinine &gt;3.5 mg/dL).&#xD;
  &#xD;
            -  pregnancy.&#xD;
  &#xD;
            -  glucose 6-phosphate-dehydrogenase deficiency.&#xD;
  &#xD;
            -  known allergy to MB or food dyes and the use of nitrates within the last 3 days.&#xD;
  &#xD;
            -  more than 24 hrs since initiation of norepinephrine.&#xD;
  &#xD;
            -  other causes of shock than sepsis .&#xD;
  &#xD;
            -  recent intake (4-weeks) of selective serotonin re-uptake inhibitors or MAOi.&#xD;
  &#xD;
            -  refusal of the patient guardian to participate.&#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_official>
      <last_name>Ehab H Shaker, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>National Cancer Institute (NCI)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Ehab H Shaker, MD</last_name>
      <phone>01222438820</phone>
      <email>ehabhanafy2006@yahoo.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Mai Elrawas, MD</last_name>
      <phone>01222177242</phone>
      <email>mai.elrawas@nci.cu.edu.eg</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>National Cancer Institute</name>
        <address>
          <city>Cairo</city>
          <zip>12588</zip>
          <country>Egypt</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Ehab H Shaker, MD</last_name>
        <phone>01222438820</phone>
        <email>ehabhanafy2006@yahoo.com</email>
      </contact>
    </location>
    <location_countries>
      <country>Egypt</country>
    </location_countries>
    <results_reference>
      <citation>Chalise SN, Sahib TA, Boyer GA, Pathak V. Methylene Blue in Refractory Shock. Cureus. 2022 Nov 6;14(11):e31158. doi: 10.7759/cureus.31158. eCollection 2022 Nov.</citation>
      <PMID>36505110</PMID>
    </results_reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 15, 2023</study_first_submitted>
    <study_first_submitted_qc>August 15, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>August 15, 2023</last_update_submitted>
    <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 22, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>National Cancer Institute, Egypt</investigator_affiliation>
      <investigator_full_name>Ehab Hanafy Shaker</investigator_full_name>
      <investigator_title>Associate Professor of Anesthesia, ICU and Pain management</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Shock, Septic</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Methylene Blue</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>After study completion and study publication we can share IPD upon request.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06005558
  org study id: Methylene blue
  nct id: NCT06005558
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  The main aim of this study is to examine the various effects of continuous methylene blue
        infusion in septic cancer patients and to compare it with the traditional infusion of
        noradrenaline in such patients .
  Exaggerated host response to infection, may result in sepsis, which is life-threatening organ
        dysfunction . Though considered the number one cause of in-hospital deaths , it can be
        treatable with early prompt interventions.
  
        The 2021 SSC Guidelines use the Third International Consensus definitions, also known as
        Sepsis-3. Where sepsis is defined as "life-threatening organ dysfunction caused by a
        dysregulated host response to infection." Organ dysfunction is evidenced by an increased
        score of 2 or more in the Quick Sequential [Sepsis-related] Organ Failure Assessment (QSOFA),
        and septic shock is considered as "a subset of sepsis in which particularly profound
        circulatory, cellular, and metabolic abnormalities are associated with a greater risk of
        mortality than with sepsis alone." To diagnose septic shock, an euvolemic patient must
        require vasopressor support to achieve a mean arterial pressure of at least 65 mm Hg and have
        a lactate level above 2 mmol/L.
  
        The triad of intravenous fluid, vasopressors and antibiotics in the first hour is the
        mainstay of septic shock management. Aim of management is to maintain patient hemodynamically
        stable until antibiotics kick in and fight infection. In case of non-responders, low dose
        corticosteroids are prescribed. Other drugs need to be studied to also help in cases of
        non-responders and to improve outcome in general. Methylene blue (MB) is a nitric oxide
        inhibitor that can counteract the vasodilatation in early septic shock.
  
        Nitric oxide (NO) activates soluble guanylyl cyclase (sGC) which activates cyclic guanosine
        monophosphate (cGMP)-dependent protein kinases (PKGs) that cause vasodilatation. Methylene
        blue selectively blocks sGC and inhibits iNOS. Therefore, it selectively acts on the
        microcirculation.
  
        Onset of action of intravenous MB is 30-60 min. Peak concentration at 30 min. It is excreted
        through bile and fecal routes plus through the kidneys. Due to the short Plasma half-life of
        5-6 hours, some studies used continuous infusion of 0.25-2 mg/kg/h, for up to 3 days
        following the initial bolus dose
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Care Provider)
  measure: Discontinuation of vasopressor
  time frame: 7 days
  description: Time for noradrenaline discontinuation
  measure: Mortality
  time frame: 28 days
  description: Number of deaths
  arm group label: Normal saline
  arm group type: Active Comparator
  description: 30 patients will receive placebo of 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of Nacl for 72 hours.
  arm group label: methylene blue low dose
  arm group type: Active Comparator
  description: 30 patients will receive a bolus of MB 1mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
  arm group label: methylene blue high dose
  arm group type: Active Comparator
  description: 30 patients will receive a bolus of MB 4mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
  intervention type: Drug
  intervention name: Normal saline
  description: 100 ml 0.9% Nacl over 20 minutes, followed by continuous infusion of normal saline for 72 hours.
  arm group label: methylene blue high dose
  arm group label: methylene blue low dose
  other name: Control
  intervention type: Drug
  intervention name: Methylene Blue low dose
  description: A bolus of MB 1mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
  arm group label: Normal saline
  arm group label: methylene blue high dose
  other name: Low dose
  intervention type: Drug
  intervention name: Methylene Blue high dose
  description: A bolus of MB 4mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
  arm group label: Normal saline
  arm group label: methylene blue low dose
  other name: High dose
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Ehab H Shaker, MD
  role: Principal Investigator
  affiliation: National Cancer Institute (NCI)
  last name: Ehab H Shaker, MD
  phone: 01222438820
  email: ehabhanafy2006@yahoo.com
  last name: Mai Elrawas, MD
  phone: 01222177242
  email: mai.elrawas@nci.cu.edu.eg
  facility: 
  status: Recruiting
  contact: 
  country: Egypt
  citation: Chalise SN, Sahib TA, Boyer GA, Pathak V. Methylene Blue in Refractory Shock. Cureus. 2022 Nov 6;14(11):e31158. doi: 10.7759/cureus.31158. eCollection 2022 Nov.
  PMID: 36505110
  responsible party type: Principal Investigator
  investigator affiliation: National Cancer Institute, Egypt
  investigator full name: Ehab Hanafy Shaker
  investigator title: Associate Professor of Anesthesia, ICU and Pain management
  mesh term: Shock, Septic
  mesh term: Methylene Blue
  sharing ipd: No
  ipd description: After study completion and study publication we can share IPD upon request.