<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/NCT02982148</url>
  </required_header>
  <id_info>
    <org_study_id>SLNB5010</org_study_id>
    <nct_id>NCT02982148</nct_id>
  </id_info>
  <brief_title>Methylene Blue Intradermal Injection for Sentinel Lymph Node Biopsy for Breast Cancer Patients</brief_title>
  <official_title>Comparison Between Intradermal Injection and Subcutaneous Injection With Methylene Blue for Sentinel Lymph Node Biopsy for Breast Cancer Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to compare the effectiveness of intradermal injection and subcutaneous&#xD;
      injection with methylene blue for early-stage breast cancer patients who need sentinel lymph&#xD;
      node biopsy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After fully informing and consent, patients recruited would be randomized 1:1 to intradermal&#xD;
      injection group and subcutaneous injection group. Investigators aimed to find out the&#xD;
      difference in sentinel lymph nodes detected rate, blue lymphatic detected rate and&#xD;
      complication incidence between the two groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>May 2015</start_date>
  <completion_date type="Anticipated">January 2017</completion_date>
  <primary_completion_date type="Anticipated">January 2017</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>detective rate of sentinel lymph node</measure>
    <time_frame>through study completion, an average of 1.5 year</time_frame>
    <description>Right after each of the sentinel lymph node biopsy, the investigators would collect data of whether it was successful or not and the amount of sentinel lymph nodes that shown out by the certain intervention.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>detective rate of blue lymphatic</measure>
    <time_frame>through study completion, an average of 1.5 year</time_frame>
    <description>The researcher would record if the surgeons could see blue lymphatic during the procedure of locating sentinel lymph node in use of the certain intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>incidence of adverse events</measure>
    <time_frame>1 month after surgery</time_frame>
    <description>One month after surgery, researchers would record if any adverse events appeared by phone call follow-up.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">352</enrollment>
  <condition>Breast Cancer Female</condition>
  <condition>Early-Stage Breast Cancer</condition>
  <condition>Sentinel Lymph Node</condition>
  <arm_group>
    <arm_group_label>methylene blue intradermal injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For patients randomized to intradermal injection before surgery began, 0.5ml 0.4% methylene blue(1ml methylene blue mixed up with 1.5ml saline) would be injected sub-areola (12 o'clock , 3 o'clock , 6 o'clock , 9 o'clock) intradermally, 0.1ml respectively, or peritumoral depending on the tumor location, 10-15 minutes before skin incision. The breast was massaged for 5 minutes to facilitate the identification of blue lymphatic vessels and the lymph nodes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>methylene blue subcutaneous injection</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>For patients randomized to subcutaneous injection before surgery began, 0.5ml 100% methylene blue would be injected sub-areola subcutaneously(12 o'clock , 3 o'clock , 6 o'clock , 9 o'clock), 0.1ml respectively or peritumoral depending on the tumor location, 10-15 minutes before skin incision. The breast was massaged for 5 minutes to facilitate the identification of blue lymphatic vessels and the lymph nodes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>methylene blue intradermal injection</intervention_name>
    <description>Methylene blue has been prove to be effective and safe as a blue dye for sentinel lymph node biopsy in early breast cancer patient. But it was also reported by some article that adverse skin lesions appeared after methylene blue injections for sentinel lymph node localization. But the effectiveness and safety of methylene blue intradermal injection has not yet been investigated.</description>
    <arm_group_label>methylene blue intradermal injection</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>methylene blue subcutaneous injection</intervention_name>
    <description>Methylene blue subcutaneous injection has become one of the standard method for sentinel lymph node biopsy for breast cancer patients. In such case, we use this method to be an active comparator for the intradermal injection group.</description>
    <arm_group_label>methylene blue subcutaneous injection</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  who sign the informed consent form&#xD;
&#xD;
          -  pathological diagnosed, without distant metastasis, early stage invasive breast cancer&#xD;
             patients&#xD;
&#xD;
          -  did not undergo neoadjuvant chemotherapy, endocrinotherapy or targeted therapy&#xD;
             previously&#xD;
&#xD;
          -  without breast and axillary surgery history&#xD;
&#xD;
          -  Ejection fraction score in normal range accord to cardiac doppler&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group score ≤0-2&#xD;
&#xD;
          -  axillary lymph node clinical negative&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  any history of malignant tumor within five years&#xD;
&#xD;
          -  diagnosis of multi-center, multi-focal or bilateral breast cancer&#xD;
&#xD;
          -  history of breast tumor incision biopsy or vacuum-assisted biopsy&#xD;
&#xD;
          -  methylene blue allergic&#xD;
&#xD;
          -  appear with severe systematic disease or disfunction of any organ&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fengxi Su, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kai Chen, M.D.</last_name>
    <phone>86-15920164730</phone>
  </overall_contact>
  <location>
    <facility>
      <name>Sun-Yat-Sen Memorial Hospital of Sun-Yat-Sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510120</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kai Chen, M.D.</last_name>
      <phone>86-15920164730</phone>
      <email>chenkai23@mail.sysu.edu.cn</email>
    </contact>
    <investigator>
      <last_name>Erwei Song, M.D., Ph.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kai Chen, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Stradling B, Aranha G, Gabram S. Adverse skin lesions after methylene blue injections for sentinel lymph node localization. Am J Surg. 2002 Oct;184(4):350-2. doi: 10.1016/s0002-9610(02)00945-5.</citation>
    <PMID>12383900</PMID>
  </reference>
  <reference>
    <citation>Teknos D, Ramcharan A, Oluwole SF. Pulmonary edema associated with methylene blue dye administration during sentinel lymph node biopsy. J Natl Med Assoc. 2008 Dec;100(12):1483-4. doi: 10.1016/s0027-9684(15)31552-2.</citation>
    <PMID>19110921</PMID>
  </reference>
  <reference>
    <citation>Abdollahi A, Jangjoo A, Dabbagh Kakhki VR, Rasoul Zakavi S, Memar B, Naser Forghani M, Mehrabibahar M, Sadeghi R. Factors affecting sentinel lymph node detection failure in breast cancer patients using intradermal injection of the tracer. Rev Esp Med Nucl. 2010 Mar-Apr;29(2):73-7. doi: 10.1016/j.remn.2009.10.001. Epub 2009 Nov 22.</citation>
    <PMID>19931946</PMID>
  </reference>
  <reference>
    <citation>Golshan M, Nakhlis F. Can methylene blue only be used in sentinel lymph node biopsy for breast cancer? Breast J. 2006 Sep-Oct;12(5):428-30. doi: 10.1111/j.1075-122X.2006.00299.x.</citation>
    <PMID>16958960</PMID>
  </reference>
  <reference>
    <citation>Gumus M, Gumus H, Jones SE, Jones PA, Sever AR, Weeks J. How long will I be blue? Prolonged skin staining following sentinel lymph node biopsy using intradermal patent blue dye. Breast Care (Basel). 2013 Jun;8(3):199-202. doi: 10.1159/000352092.</citation>
    <PMID>24415970</PMID>
  </reference>
  <reference>
    <citation>Scheutz F. Drug addicts and local analgesia--effectivity and general side effects. Scand J Dent Res. 1982 Aug;90(4):299-305. doi: 10.1111/j.1600-0722.1982.tb00741.x.</citation>
    <PMID>6957969</PMID>
  </reference>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 29, 2016</study_first_submitted>
  <study_first_submitted_qc>December 2, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <last_update_submitted>December 2, 2016</last_update_submitted>
  <last_update_submitted_qc>December 2, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 5, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</investigator_affiliation>
    <investigator_full_name>Fengxi Su</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </responsible_party>
  <keyword>sentinel lymph node biopsy</keyword>
  <keyword>methylene blue</keyword>
  <keyword>intradermal injection</keyword>
  <keyword>subcutaneous injection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</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>
  </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/NCT02982148
org study id: SLNB5010
nct id: NCT02982148
lead sponsor: 
has dmc: No
This study is designed to compare the effectiveness of intradermal injection and subcutaneous
      injection with methylene blue for early-stage breast cancer patients who need sentinel lymph
      node biopsy.
After fully informing and consent, patients recruited would be randomized 1:1 to intradermal
      injection group and subcutaneous injection group. Investigators aimed to find out the
      difference in sentinel lymph nodes detected rate, blue lymphatic detected rate and
      complication incidence between the two groups.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: detective rate of sentinel lymph node
time frame: through study completion, an average of 1.5 year
description: Right after each of the sentinel lymph node biopsy, the investigators would collect data of whether it was successful or not and the amount of sentinel lymph nodes that shown out by the certain intervention.
measure: detective rate of blue lymphatic
time frame: through study completion, an average of 1.5 year
description: The researcher would record if the surgeons could see blue lymphatic during the procedure of locating sentinel lymph node in use of the certain intervention.
measure: incidence of adverse events
time frame: 1 month after surgery
description: One month after surgery, researchers would record if any adverse events appeared by phone call follow-up.
arm group label: methylene blue intradermal injection
arm group type: Experimental
description: For patients randomized to intradermal injection before surgery began, 0.5ml 0.4% methylene blue(1ml methylene blue mixed up with 1.5ml saline) would be injected sub-areola (12 o'clock , 3 o'clock , 6 o'clock , 9 o'clock) intradermally, 0.1ml respectively, or peritumoral depending on the tumor location, 10-15 minutes before skin incision. The breast was massaged for 5 minutes to facilitate the identification of blue lymphatic vessels and the lymph nodes.
arm group label: methylene blue subcutaneous injection
arm group type: Active Comparator
description: For patients randomized to subcutaneous injection before surgery began, 0.5ml 100% methylene blue would be injected sub-areola subcutaneously(12 o'clock , 3 o'clock , 6 o'clock , 9 o'clock), 0.1ml respectively or peritumoral depending on the tumor location, 10-15 minutes before skin incision. The breast was massaged for 5 minutes to facilitate the identification of blue lymphatic vessels and the lymph nodes.
intervention type: Device
intervention name: methylene blue intradermal injection
description: Methylene blue has been prove to be effective and safe as a blue dye for sentinel lymph node biopsy in early breast cancer patient. But it was also reported by some article that adverse skin lesions appeared after methylene blue injections for sentinel lymph node localization. But the effectiveness and safety of methylene blue intradermal injection has not yet been investigated.
arm group label: methylene blue intradermal injection
intervention type: Device
intervention name: methylene blue subcutaneous injection
description: Methylene blue subcutaneous injection has become one of the standard method for sentinel lymph node biopsy for breast cancer patients. In such case, we use this method to be an active comparator for the intradermal injection group.
arm group label: methylene blue subcutaneous injection
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Fengxi Su, M.D.
role: Principal Investigator
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
last name: Kai Chen, M.D.
phone: 86-15920164730
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: China
citation: Stradling B, Aranha G, Gabram S. Adverse skin lesions after methylene blue injections for sentinel lymph node localization. Am J Surg. 2002 Oct;184(4):350-2. doi: 10.1016/s0002-9610(02)00945-5.
PMID: 12383900
citation: Teknos D, Ramcharan A, Oluwole SF. Pulmonary edema associated with methylene blue dye administration during sentinel lymph node biopsy. J Natl Med Assoc. 2008 Dec;100(12):1483-4. doi: 10.1016/s0027-9684(15)31552-2.
PMID: 19110921
citation: Abdollahi A, Jangjoo A, Dabbagh Kakhki VR, Rasoul Zakavi S, Memar B, Naser Forghani M, Mehrabibahar M, Sadeghi R. Factors affecting sentinel lymph node detection failure in breast cancer patients using intradermal injection of the tracer. Rev Esp Med Nucl. 2010 Mar-Apr;29(2):73-7. doi: 10.1016/j.remn.2009.10.001. Epub 2009 Nov 22.
PMID: 19931946
citation: Golshan M, Nakhlis F. Can methylene blue only be used in sentinel lymph node biopsy for breast cancer? Breast J. 2006 Sep-Oct;12(5):428-30. doi: 10.1111/j.1075-122X.2006.00299.x.
PMID: 16958960
citation: Gumus M, Gumus H, Jones SE, Jones PA, Sever AR, Weeks J. How long will I be blue? Prolonged skin staining following sentinel lymph node biopsy using intradermal patent blue dye. Breast Care (Basel). 2013 Jun;8(3):199-202. doi: 10.1159/000352092.
PMID: 24415970
citation: Scheutz F. Drug addicts and local analgesia--effectivity and general side effects. Scand J Dent Res. 1982 Aug;90(4):299-305. doi: 10.1111/j.1600-0722.1982.tb00741.x.
PMID: 6957969
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
investigator full name: Fengxi Su
investigator title: professor
mesh term: Breast Neoplasms
mesh term: Methylene Blue
sharing ipd: No