<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/NCT04421495</url>
  </required_header>
  <id_info>
    <org_study_id>LCSY-TB-2020-002</org_study_id>
    <nct_id>NCT04421495</nct_id>
  </id_info>
  <brief_title>Safety and Effectiveness of Delamanid-containing Regimen for MDR-TB Patients in China</brief_title>
  <official_title>Safety and Effectiveness of Delamanid-containing Regimen for Treatment of Patients With Multidrug-resistant Tuberculosis in China</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing Chest Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing Chest Hospital</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>
      The purpose of this study is to monitor and evaluate the safety and effectiveness of&#xD;
      Delamanid in combination with an optimal background regimen (OBR) of anti-TB drugs for&#xD;
      treatment of MDR-TB.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-arm, multicenter, phase #, open-label trial to evaluate the safety and&#xD;
      effectiveness of delamanid-containing regimen in men and women aged 18 to 65 years with&#xD;
      microbiologically confirmed pulmonary MDR-TB in China. A target of 600 participants will be&#xD;
      enrolled. The study will consist of a screening phase of up to 8 weeks, an open-label study&#xD;
      treatment phase of 13-20 months, and a follow-up phase of 12-month after end of study&#xD;
      treatment. During the study treatment phase, participants will receive an MDR-TB regimen&#xD;
      consisting of 24 weeks of delamanid in combination with 13-20 months of a background regimen.&#xD;
&#xD;
      Participants will be instructed to take their assigned dose of delamanid with at least 3&#xD;
      additional probably effective background drugs according to national and international&#xD;
      guidelines. Delamanid dosage will be 100 mg twice daily (b.i.d.) for 24 weeks.&#xD;
&#xD;
      Safety evaluations will include monitoring of AEs, visual acuity testing, routine blood&#xD;
      examinations (such as hematology, clinical chemistry, HIV, TSH [for subjects receiving PTO]&#xD;
      measurements), urinalysis, and electrocardiograms (ECGs). Participants will initiate&#xD;
      treatment with the study regimen if they meet the study eligibility criteria.The end of study&#xD;
      will be considered as the last contact for the last participant in the study.&#xD;
&#xD;
      A participant will be considered to have completed the study if he or she has completed the&#xD;
      13-20 months study treatment phase and the required post-treatment follow-up phase.&#xD;
      Participants who prematurely discontinue study treatment (unless they withdraw consent) will&#xD;
      be followed up for 12 months after end of delamanid treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 16, 2020</start_date>
  <completion_date type="Anticipated">July 16, 2024</completion_date>
  <primary_completion_date type="Actual">June 16, 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of participants experiencing all-cause mortality</measure>
    <time_frame>from enrollment to the completion of the trial ,an average of 30-32months</time_frame>
    <description>the percentage of participants who died during the trial.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of participants experiencing treatment-emergent AEs</measure>
    <time_frame>the whole treatment phase,an average of 18-20 months</time_frame>
    <description>the percentage of participants who experienced adverse effect during treatment phase.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Percentage of Participants With Sputum Culture Conversion</measure>
    <time_frame>up to 24 weeks after enrollment</time_frame>
    <description>Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multidrug-resistant tuberculosis (MDR-TB) taken at least 25 days apart.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Median Time to Sputum Culture Conversion</measure>
    <time_frame>upto 24 weeks after enrollment</time_frame>
    <description>Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multidrug-resistant tuberculosis (MDR-TB) taken at least 25 days apart.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">608</enrollment>
  <condition>Multidrug Resistant Tuberculosis</condition>
  <arm_group>
    <arm_group_label>delamanid containing regimen arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>the only one arm to be studied with delamid-containing regimen.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Delamanid</intervention_name>
    <description>the eligible patients will be give damanid-containing regimen</description>
    <arm_group_label>delamanid containing regimen arm</arm_group_label>
    <other_name>anti-TB new drug containing regimen</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with microbiologically confirmed multidrug-resistant/rifampicin resistant&#xD;
             tuberculosis ;&#xD;
&#xD;
          2. Age 18 to 65 years old;&#xD;
&#xD;
          3. MDR-TB treatment has not been started, or treatment has been started but treatment&#xD;
             regimen need to be intensified;&#xD;
&#xD;
          4. According to the guidelines of WHO's consolidated guidelines for the treatment of&#xD;
             drug-resistant TB and the consensus of Chinese experts in the treatment of&#xD;
             multidrug-resistant and rifampicin resistant TB (2019 edition), effective treatment&#xD;
             regimens can only be formed by adding Delamanid based on the results of drug&#xD;
             susceptibility testing and the previous treatment history;&#xD;
&#xD;
          5. No history of respiratory failure, no history of cardiac dysfunction and clinically&#xD;
             significant arrhythmia, QTcF &lt; 450ms;&#xD;
&#xD;
          6. Patients should be able to take medicines and clinical monitoring according to the&#xD;
             requirements of the trial during the treatment and follow-up phases, and adverse&#xD;
             effects should be reported to the responsible doctor timely ;&#xD;
&#xD;
          7. Patients should sign the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. A history of allergy to nitroimidazole and pyrrole drugs such as Delamanid,&#xD;
             metronidazole, tinidazole, or any excipient.&#xD;
&#xD;
          2. Serum transaminase increased ≥3 times the upper limit of normal value or total&#xD;
             bilirubin increased ≥2.5 times the upper limit of normal, serum albumin &lt;2.8 g / dL,&#xD;
             severe renal impairment.&#xD;
&#xD;
          3. Taking strong CYP3A4 inducer drugs (such as carbamazepine).&#xD;
&#xD;
          4. Is known to be pregnant (or planning to become pregnant) .&#xD;
&#xD;
          5. Participants took part in trials of other new unlisted drugs within the past three&#xD;
             months;&#xD;
&#xD;
          6. Congenital QT interval prolongation is known or has any disease that may prolong the&#xD;
             QT interval or QTc no less than 500 ms;&#xD;
&#xD;
          7. A history of symptomatic arrhythmia or suffering from clinically related bradycardia;&#xD;
&#xD;
          8. Any cardiac disease that can induce arrhythmias, such as severe hypertension, left&#xD;
             ventricular hypertrophy (including hypertrophic cardiomyopathy), or congestive heart&#xD;
             failure with reduced left ventricular ejection fraction;&#xD;
&#xD;
          9. Electrolyte disturbance, especially hypokalemia, hypocalcemia or hypomagnesemia;&#xD;
&#xD;
         10. Taking drugs known to prolong the QT interval such as the following drugs (but not&#xD;
             limited to) :&#xD;
&#xD;
             ① Anti-arrhythmic drugs, such as amiodarone, disopyramide, dofetilide, ibutilide,&#xD;
             procainamide, quinidine, hydroquinidine, sotalol, etc .;&#xD;
&#xD;
               -  Antipsychotic drugs, such as phenothiazine, sertindole, sultopride,&#xD;
                  chlorpromazine, haloperidol, mesoridazine, pimozide or thioridazine, and&#xD;
                  antidepressants; ③ Certain antibiotics, including:&#xD;
&#xD;
                    -  Macrolides, such as erythromycin, clarithromycin, etc ;&#xD;
&#xD;
                    -  Moxifloxacin, Sparfloxacin;&#xD;
&#xD;
                    -  Triazole antifungal drugs;&#xD;
&#xD;
                    -  Spray him with amidine;&#xD;
&#xD;
                    -  Saquinavir;&#xD;
&#xD;
                       ④ Some non-sedative antihistamines, such as terfenadine, astemizole,&#xD;
                       mizolastine, etc.&#xD;
&#xD;
         11. Other drugs with protential cardiac risk : cisapride, haloperidol, domperidone,&#xD;
             bepridil, diphemanil, probucol, dimepheptanol, methadone, vinblastine, arsenic&#xD;
             trioxide.&#xD;
&#xD;
        Deletion criteria:&#xD;
&#xD;
          1. Those who are found to have exclusion items after enrolled;&#xD;
&#xD;
          2. Serious adverse reactions caused by Delamanid, such as allergic reactions, mental&#xD;
             disorders, and liver injury (transaminases increase greater than 3 times the upper&#xD;
             limit of normal value or total bilirubin increase greater than 2.5 times the upper&#xD;
             limit of normal);&#xD;
&#xD;
          3. QTcF ≥500ms or clinically significant ventricular arrhythmia is confirmed;&#xD;
&#xD;
          4. The expert group made decision that it is not appropriate for the patient to continue&#xD;
             the treatment with Delamanid;&#xD;
&#xD;
          5. The patient cannot tolerate the background treatment regimen, or the modified&#xD;
             background treatment regimen cannot meet the 3 definitive sensitive drugs or 4&#xD;
             probably sensitive drugs;&#xD;
&#xD;
          6. The patient requests dropout.&#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>Liang Li</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beijing Chest Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Chest Hospital, Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <zip>101149</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Changsha Central Hospital</name>
      <address>
        <city>Changsha</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Public Health Clinical Center of Chengdu</name>
      <address>
        <city>Chengdu</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chongqing Infectious Disease Medical Center</name>
      <address>
        <city>Chongqing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fuzhou Pulmonary Hospital of Fujian</name>
      <address>
        <city>Fuzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guangzhou Chest Hospital</name>
      <address>
        <city>Guangzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guiyang Public Health Clinical Center</name>
      <address>
        <city>Guiyang</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heilongjiang Province center for tuberculosis Control and Prevention</name>
      <address>
        <city>Haerbin</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hangzhou Red Cross Hospital</name>
      <address>
        <city>Hangzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jiamusi Tumor Hospital</name>
      <address>
        <city>Jiamusi</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tuberculosis Hospital in Jilin Province</name>
      <address>
        <city>Jilin</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shandong Provincial Chest Hospital</name>
      <address>
        <city>Jinan</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Third People's Hospital of Kunming City</name>
      <address>
        <city>Kunming</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lanzhou Pulmonary Hospital</name>
      <address>
        <city>Lanzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Longtan Hospital of Guangxi Zhuang Autonomous Region</name>
      <address>
        <city>Liuzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jiangxi Chest (Third People) Hospital</name>
      <address>
        <city>Nanchang</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Pulmonary Hospital</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hebei Chest Hospital</name>
      <address>
        <city>Shijiangzhuang</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Fifth People Hospital of Suzhou</name>
      <address>
        <city>Suzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Fourth People's Hospital of Taiyuan</name>
      <address>
        <city>Taiyuan</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wuhan Institute For Tuberculosis Control</name>
      <address>
        <city>Wuhan</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wuhan Jinyintan Hospital</name>
      <address>
        <city>Wuhan</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Xi'an Chest Hospital</name>
      <address>
        <city>Xi'an</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanxi Provincial Tuberculosis Institute</name>
      <address>
        <city>Xian</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henan Provincial Chest Hospital</name>
      <address>
        <city>Zhengzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>July 5, 2022</last_update_submitted>
  <last_update_submitted_qc>July 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beijing Chest Hospital</investigator_affiliation>
    <investigator_full_name>Liang Li</investigator_full_name>
    <investigator_title>Vice president</investigator_title>
  </responsible_party>
  <keyword>safety</keyword>
  <keyword>Delamanid</keyword>
  <keyword>effectiveness</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
    <mesh_term>Tuberculosis, Multidrug-Resistant</mesh_term>
  </condition_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/NCT04421495
org study id: LCSY-TB-2020-002
nct id: NCT04421495
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to monitor and evaluate the safety and effectiveness of
      Delamanid in combination with an optimal background regimen (OBR) of anti-TB drugs for
      treatment of MDR-TB.
This is a single-arm, multicenter, phase #, open-label trial to evaluate the safety and
      effectiveness of delamanid-containing regimen in men and women aged 18 to 65 years with
      microbiologically confirmed pulmonary MDR-TB in China. A target of 600 participants will be
      enrolled. The study will consist of a screening phase of up to 8 weeks, an open-label study
      treatment phase of 13-20 months, and a follow-up phase of 12-month after end of study
      treatment. During the study treatment phase, participants will receive an MDR-TB regimen
      consisting of 24 weeks of delamanid in combination with 13-20 months of a background regimen.

      Participants will be instructed to take their assigned dose of delamanid with at least 3
      additional probably effective background drugs according to national and international
      guidelines. Delamanid dosage will be 100 mg twice daily (b.i.d.) for 24 weeks.

      Safety evaluations will include monitoring of AEs, visual acuity testing, routine blood
      examinations (such as hematology, clinical chemistry, HIV, TSH [for subjects receiving PTO]
      measurements), urinalysis, and electrocardiograms (ECGs). Participants will initiate
      treatment with the study regimen if they meet the study eligibility criteria.The end of study
      will be considered as the last contact for the last participant in the study.

      A participant will be considered to have completed the study if he or she has completed the
      13-20 months study treatment phase and the required post-treatment follow-up phase.
      Participants who prematurely discontinue study treatment (unless they withdraw consent) will
      be followed up for 12 months after end of delamanid treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of participants experiencing all-cause mortality
time frame: from enrollment to the completion of the trial ,an average of 30-32months
description: the percentage of participants who died during the trial.
measure: Proportion of participants experiencing treatment-emergent AEs
time frame: the whole treatment phase,an average of 18-20 months
description: the percentage of participants who experienced adverse effect during treatment phase.
measure: The Percentage of Participants With Sputum Culture Conversion
time frame: up to 24 weeks after enrollment
description: Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multidrug-resistant tuberculosis (MDR-TB) taken at least 25 days apart.
measure: The Median Time to Sputum Culture Conversion
time frame: upto 24 weeks after enrollment
description: Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multidrug-resistant tuberculosis (MDR-TB) taken at least 25 days apart.
arm group label: delamanid containing regimen arm
arm group type: Experimental
description: the only one arm to be studied with delamid-containing regimen.
intervention type: Drug
intervention name: Delamanid
description: the eligible patients will be give damanid-containing regimen
arm group label: delamanid containing regimen arm
other name: anti-TB new drug containing regimen
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Liang Li
role: Principal Investigator
affiliation: Beijing Chest Hospital
facility: 
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country: China
responsible party type: Principal Investigator
investigator affiliation: Beijing Chest Hospital
investigator full name: Liang Li
investigator title: Vice president
mesh term: Tuberculosis
mesh term: Tuberculosis, Multidrug-Resistant