<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/NCT02254655</url>
  </required_header>
  <id_info>
    <org_study_id>E-2012-063</org_study_id>
    <secondary_id>No. BWS11J067</secondary_id>
    <nct_id>NCT02254655</nct_id>
  </id_info>
  <brief_title>The Effect of Puerarin Injection on Carotid Intima-Media Thickness in Patients With Rheumatoid Arthritis</brief_title>
  <official_title>The Effect of Puerarin Injection on Carotid Intima-Media Thickness in Patients With Rheumatoid Arthritis, a Controlled and Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chengdu PLA General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chengdu PLA General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to access the effect (week 12/week 24) of puerarin injection on&#xD;
      carotid intima-media thickness (CIMT) in rheumatoid arthritis (RA) patients despite routine&#xD;
      anti-rheumatic treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -  Controlled, randomized trial&#xD;
&#xD;
        -  RA patients under routine anti-rheumatic care were randomized to receive the treatment&#xD;
           with or without 400 mg puerarin injection&#xD;
&#xD;
        -  Assessments were made at entry, 12 and 24 weeks&#xD;
&#xD;
        -  The overall sample size was assessed before the enrollment&#xD;
&#xD;
        -  Randomization was performed using concealed random allocation method&#xD;
&#xD;
        -  The collected data was processed and assessed by two reviewers&#xD;
&#xD;
        -  All the measurement and analysis procedures concerning CIMT were performed by a single&#xD;
           ultra sonographer and a single reader, who were blinded to patient profiles and group&#xD;
           assignment&#xD;
&#xD;
        -  The reproducibility of the ultrasonographic method was test before the trial&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2013</start_date>
  <completion_date type="Actual">November 2017</completion_date>
  <primary_completion_date type="Actual">September 2017</primary_completion_date>
  <phase>Phase 2</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>Supportive Care</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes from baseline in Carotid intima-media thickness at 24 weeks</measure>
    <time_frame>At 0 week, 12 weeks, 24 weeks</time_frame>
    <description>Carotid intima-media thickness (CIMT) was using a high-resolution B-mode ultrasound machine (iU22 xMATRIX, Philips, Germany). CIMT was measured twice by a single experienced operator using an 10-MHz linear vascular probe. Patients were let resting in a relaxed supine position, with the head turned gently to the contralateral side when the electrocardiogram was recorded. The imaging system (QLab 6.0, Philips, Germany) was applied to measure the CIMT signals from the proximal internal carotid artery (the arterial segment 10 mm distal to the carotid bifurcation), the carotid bulb and the distal common carotid artery (the arterial segment 10 mm proximal to the carotid bulb). The mean CIMT was calculated from the value of five arterial segments. All the measurement and analysis procedures were performed by a single ultra sonographer and a single reader, who were blinded to patient profiles and group assignment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>low-density lipoprotein cholesterol (LDL-C)</measure>
    <time_frame>at 0 week, 12 weeks, 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>erythrocyte sedimentation rate (ESR)</measure>
    <time_frame>at 0 week, 12 weeks, 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C reactive protein (CRP)</measure>
    <time_frame>at 0 week, 12 weeks, 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total cholesterol (TC)</measure>
    <time_frame>at 0 week, 12 weeks, 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>triglycerides (TGs)</measure>
    <time_frame>at 0 week, 12 weeks, 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tumor necrosis factor (TNFα)</measure>
    <time_frame>at 0 week，12 weeks, 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>interleukin-8 (IL-8)</measure>
    <time_frame>at 0 week，12 weeks, 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>interleukin-1 (IL-1)</measure>
    <time_frame>at 0 week，12 weeks, 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>interleukin-6 (IL-6)</measure>
    <time_frame>at 0 week，12 weeks, 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>disease activity score in 28 joints (DAS28)</measure>
    <time_frame>at 0 week，12 weeks, 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>homeostasis model assessment (HOMA-IR)</measure>
    <time_frame>at 0 week，12 weeks, 24 weeks</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Kidney function</measure>
    <time_frame>at 0 week, 12 weeks, 24 weeks</time_frame>
    <description>from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks</description>
  </other_outcome>
  <other_outcome>
    <measure>Liver function</measure>
    <time_frame>at 0 week, 12 weeks, 24 weeks</time_frame>
    <description>from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks</description>
  </other_outcome>
  <other_outcome>
    <measure>blood cell count</measure>
    <time_frame>at 0 week, 12 weeks, 24 weeks</time_frame>
    <description>from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">119</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>Puerarin injection 400 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients were administrated with 400 mg intravenously infused puerarin injection once a day. Puerarin injection was prepared in 250 mL 0.9% sodium chloride injection before the use. The treatment course consisted of 2 weeks followed by a 15-day interval for 24 weeks. Furthermore, patients receive stable treatment with oral anti-rheumatic agents and/or non-steroidal anti-inflammatory drugs, prednisone, aspirin, statins, bone metabolism regulators and gastric mucosal protective agents on as-needed basis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Patients receive routine anti-rheumatic care only. Patients receive stable treatment with oral anti-rheumatic agents and/or non-steroidal anti-inflammatory drugs, prednisone, aspirin, statins, bone metabolism regulators and gastric mucosal protective agents on as-needed basis.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Puerarin injection 400 mg</intervention_name>
    <description>Patients receive treatment with oral anti-rheumatic agents and/or non-steroidal anti-inflammatory drugs, prednisone, aspirin, statins, bone metabolism regulators and gastric mucosal protective agents on as-needed basis.Furthermore, patients were administrated with 400 mg intravenously infused puerarin injection once a day.Each treatment course lasted for 2 weeks followed by a regular time interval of 15 days.</description>
    <arm_group_label>Puerarin injection 400 mg</arm_group_label>
    <other_name>Puerarin injection 400 mg + routine anti-rheumatic drugs</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Control</intervention_name>
    <description>Patients receive treatment with oral anti-rheumatic agents and/or non-steroidal anti-inflammatory drugs, prednisone, aspirin, statins, bone metabolism regulators and gastric mucosal protective agents on as-needed basis</description>
    <arm_group_label>Control</arm_group_label>
    <other_name>Routine anti-rheumatic drugs</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients with a definite diagnose of rheumatoid arthritis(RA) were included if they&#xD;
             met the classification criteria for RA established by the American Rheumatism&#xD;
             Association (ACR) and European League Against Rheumatism (EULAR) in 2010&#xD;
&#xD;
          -  aged from 18 to 75 years&#xD;
&#xD;
          -  without conflict to the written, informed consent signed prior to the enrollment&#xD;
&#xD;
          -  no severe hepatic or renal disorders&#xD;
&#xD;
          -  no known carotid artery stenosis&#xD;
&#xD;
          -  no coagulation disorders&#xD;
&#xD;
          -  no hypertension&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  being in pregnancy, lactation period or under a pregnancy plan&#xD;
&#xD;
          -  being allergic to the test drug&#xD;
&#xD;
          -  not compatible for the trial medication&#xD;
&#xD;
          -  without full legal capacity&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Min Yang, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>General Hospital of Chengdu Military Area Command PLA</affiliation>
  </overall_official>
  <removed_countries>
    <country>China</country>
  </removed_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>November 18, 2013</study_first_submitted>
  <study_first_submitted_qc>October 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2014</study_first_posted>
  <last_update_submitted>January 15, 2018</last_update_submitted>
  <last_update_submitted_qc>January 15, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chengdu PLA General Hospital</investigator_affiliation>
    <investigator_full_name>Yang Min</investigator_full_name>
    <investigator_title>Dr.</investigator_title>
  </responsible_party>
  <keyword>puerarin</keyword>
  <keyword>rheumatoid arthritis</keyword>
  <keyword>atherosclerosis</keyword>
  <keyword>carotid intima-media thickness</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antirheumatic Agents</mesh_term>
    <mesh_term>Puerarin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02254655
org study id: E-2012-063
secondary id: No. BWS11J067
nct id: NCT02254655
lead sponsor: 
has dmc: Yes
The purpose of this study is to access the effect (week 12/week 24) of puerarin injection on
      carotid intima-media thickness (CIMT) in rheumatoid arthritis (RA) patients despite routine
      anti-rheumatic treatment.
-  Controlled, randomized trial

        -  RA patients under routine anti-rheumatic care were randomized to receive the treatment
           with or without 400 mg puerarin injection

        -  Assessments were made at entry, 12 and 24 weeks

        -  The overall sample size was assessed before the enrollment

        -  Randomization was performed using concealed random allocation method

        -  The collected data was processed and assessed by two reviewers

        -  All the measurement and analysis procedures concerning CIMT were performed by a single
           ultra sonographer and a single reader, who were blinded to patient profiles and group
           assignment

        -  The reproducibility of the ultrasonographic method was test before the trial
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Single (Outcomes Assessor)
measure: Changes from baseline in Carotid intima-media thickness at 24 weeks
time frame: At 0 week, 12 weeks, 24 weeks
description: Carotid intima-media thickness (CIMT) was using a high-resolution B-mode ultrasound machine (iU22 xMATRIX, Philips, Germany). CIMT was measured twice by a single experienced operator using an 10-MHz linear vascular probe. Patients were let resting in a relaxed supine position, with the head turned gently to the contralateral side when the electrocardiogram was recorded. The imaging system (QLab 6.0, Philips, Germany) was applied to measure the CIMT signals from the proximal internal carotid artery (the arterial segment 10 mm distal to the carotid bifurcation), the carotid bulb and the distal common carotid artery (the arterial segment 10 mm proximal to the carotid bulb). The mean CIMT was calculated from the value of five arterial segments. All the measurement and analysis procedures were performed by a single ultra sonographer and a single reader, who were blinded to patient profiles and group assignment.
measure: low-density lipoprotein cholesterol (LDL-C)
time frame: at 0 week, 12 weeks, 24 weeks
measure: erythrocyte sedimentation rate (ESR)
time frame: at 0 week, 12 weeks, 24 weeks
measure: C reactive protein (CRP)
time frame: at 0 week, 12 weeks, 24 weeks
measure: Total cholesterol (TC)
time frame: at 0 week, 12 weeks, 24 weeks
measure: triglycerides (TGs)
time frame: at 0 week, 12 weeks, 24 weeks
measure: tumor necrosis factor (TNFα)
time frame: at 0 week，12 weeks, 24 weeks
measure: interleukin-8 (IL-8)
time frame: at 0 week，12 weeks, 24 weeks
measure: interleukin-1 (IL-1)
time frame: at 0 week，12 weeks, 24 weeks
measure: interleukin-6 (IL-6)
time frame: at 0 week，12 weeks, 24 weeks
measure: disease activity score in 28 joints (DAS28)
time frame: at 0 week，12 weeks, 24 weeks
measure: homeostasis model assessment (HOMA-IR)
time frame: at 0 week，12 weeks, 24 weeks
measure: Kidney function
time frame: at 0 week, 12 weeks, 24 weeks
description: from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks
measure: Liver function
time frame: at 0 week, 12 weeks, 24 weeks
description: from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks
measure: blood cell count
time frame: at 0 week, 12 weeks, 24 weeks
description: from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks
arm group label: Puerarin injection 400 mg
arm group type: Experimental
description: Patients were administrated with 400 mg intravenously infused puerarin injection once a day. Puerarin injection was prepared in 250 mL 0.9% sodium chloride injection before the use. The treatment course consisted of 2 weeks followed by a 15-day interval for 24 weeks. Furthermore, patients receive stable treatment with oral anti-rheumatic agents and/or non-steroidal anti-inflammatory drugs, prednisone, aspirin, statins, bone metabolism regulators and gastric mucosal protective agents on as-needed basis.
arm group label: Control
arm group type: Sham Comparator
description: Patients receive routine anti-rheumatic care only. Patients receive stable treatment with oral anti-rheumatic agents and/or non-steroidal anti-inflammatory drugs, prednisone, aspirin, statins, bone metabolism regulators and gastric mucosal protective agents on as-needed basis.
intervention type: Drug
intervention name: Puerarin injection 400 mg
description: Patients receive treatment with oral anti-rheumatic agents and/or non-steroidal anti-inflammatory drugs, prednisone, aspirin, statins, bone metabolism regulators and gastric mucosal protective agents on as-needed basis.Furthermore, patients were administrated with 400 mg intravenously infused puerarin injection once a day.Each treatment course lasted for 2 weeks followed by a regular time interval of 15 days.
arm group label: Puerarin injection 400 mg
other name: Puerarin injection 400 mg + routine anti-rheumatic drugs
intervention type: Drug
intervention name: Control
description: Patients receive treatment with oral anti-rheumatic agents and/or non-steroidal anti-inflammatory drugs, prednisone, aspirin, statins, bone metabolism regulators and gastric mucosal protective agents on as-needed basis
arm group label: Control
other name: Routine anti-rheumatic drugs
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Min Yang, Ph.D.
role: Principal Investigator
affiliation: General Hospital of Chengdu Military Area Command PLA
country: China
responsible party type: Principal Investigator
investigator affiliation: Chengdu PLA General Hospital
investigator full name: Yang Min
investigator title: Dr.
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Antirheumatic Agents
mesh term: Puerarin