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Safety and Effectiveness of Delamanid-containing Regimen for MDR-TB Patients in China

Primary Purpose

Multidrug Resistant Tuberculosis

Status
Active
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Delamanid
Sponsored by
Beijing Chest Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multidrug Resistant Tuberculosis focused on measuring safety, Delamanid, effectiveness

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients with microbiologically confirmed multidrug-resistant/rifampicin resistant tuberculosis ;
  2. Age 18 to 65 years old;
  3. MDR-TB treatment has not been started, or treatment has been started but treatment regimen need to be intensified;
  4. According to the guidelines of WHO's consolidated guidelines for the treatment of drug-resistant TB and the consensus of Chinese experts in the treatment of multidrug-resistant and rifampicin resistant TB (2019 edition), effective treatment regimens can only be formed by adding Delamanid based on the results of drug susceptibility testing and the previous treatment history;
  5. No history of respiratory failure, no history of cardiac dysfunction and clinically significant arrhythmia, QTcF < 450ms;
  6. Patients should be able to take medicines and clinical monitoring according to the requirements of the trial during the treatment and follow-up phases, and adverse effects should be reported to the responsible doctor timely ;
  7. Patients should sign the informed consent.

Exclusion Criteria:

  1. A history of allergy to nitroimidazole and pyrrole drugs such as Delamanid, metronidazole, tinidazole, or any excipient.
  2. Serum transaminase increased ≥3 times the upper limit of normal value or total bilirubin increased ≥2.5 times the upper limit of normal, serum albumin <2.8 g / dL, severe renal impairment.
  3. Taking strong CYP3A4 inducer drugs (such as carbamazepine).
  4. Is known to be pregnant (or planning to become pregnant) .
  5. Participants took part in trials of other new unlisted drugs within the past three months;
  6. Congenital QT interval prolongation is known or has any disease that may prolong the QT interval or QTc no less than 500 ms;
  7. A history of symptomatic arrhythmia or suffering from clinically related bradycardia;
  8. Any cardiac disease that can induce arrhythmias, such as severe hypertension, left ventricular hypertrophy (including hypertrophic cardiomyopathy), or congestive heart failure with reduced left ventricular ejection fraction;
  9. Electrolyte disturbance, especially hypokalemia, hypocalcemia or hypomagnesemia;
  10. Taking drugs known to prolong the QT interval such as the following drugs (but not limited to) :

    ① Anti-arrhythmic drugs, such as amiodarone, disopyramide, dofetilide, ibutilide, procainamide, quinidine, hydroquinidine, sotalol, etc .;

    • Antipsychotic drugs, such as phenothiazine, sertindole, sultopride, chlorpromazine, haloperidol, mesoridazine, pimozide or thioridazine, and antidepressants; ③ Certain antibiotics, including:

      • Macrolides, such as erythromycin, clarithromycin, etc ;
      • Moxifloxacin, Sparfloxacin;
      • Triazole antifungal drugs;
      • Spray him with amidine;
      • Saquinavir;

        ④ Some non-sedative antihistamines, such as terfenadine, astemizole, mizolastine, etc.

  11. Other drugs with protential cardiac risk : cisapride, haloperidol, domperidone, bepridil, diphemanil, probucol, dimepheptanol, methadone, vinblastine, arsenic trioxide.

Deletion criteria:

  1. Those who are found to have exclusion items after enrolled;
  2. Serious adverse reactions caused by Delamanid, such as allergic reactions, mental disorders, and liver injury (transaminases increase greater than 3 times the upper limit of normal value or total bilirubin increase greater than 2.5 times the upper limit of normal);
  3. QTcF ≥500ms or clinically significant ventricular arrhythmia is confirmed;
  4. The expert group made decision that it is not appropriate for the patient to continue the treatment with Delamanid;
  5. The patient cannot tolerate the background treatment regimen, or the modified background treatment regimen cannot meet the 3 definitive sensitive drugs or 4 probably sensitive drugs;
  6. The patient requests dropout.

Sites / Locations

  • Beijing Chest Hospital, Capital Medical University
  • Changsha Central Hospital
  • Public Health Clinical Center of Chengdu
  • Chongqing Infectious Disease Medical Center
  • Fuzhou Pulmonary Hospital of Fujian
  • Guangzhou Chest Hospital
  • Guiyang Public Health Clinical Center
  • Heilongjiang Province center for tuberculosis Control and Prevention
  • Hangzhou Red Cross Hospital
  • Jiamusi Tumor Hospital
  • Tuberculosis Hospital in Jilin Province
  • Shandong Provincial Chest Hospital
  • The Third People's Hospital of Kunming City
  • Lanzhou Pulmonary Hospital
  • Longtan Hospital of Guangxi Zhuang Autonomous Region
  • Jiangxi Chest (Third People) Hospital
  • Shanghai Pulmonary Hospital
  • Hebei Chest Hospital
  • The Fifth People Hospital of Suzhou
  • The Fourth People's Hospital of Taiyuan
  • Wuhan Institute For Tuberculosis Control
  • Wuhan Jinyintan Hospital
  • Xi'an Chest Hospital
  • Shanxi Provincial Tuberculosis Institute
  • Henan Provincial Chest Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

delamanid containing regimen arm

Arm Description

the only one arm to be studied with delamid-containing regimen.

Outcomes

Primary Outcome Measures

Proportion of participants experiencing all-cause mortality
the percentage of participants who died during the trial.
Proportion of participants experiencing treatment-emergent AEs
the percentage of participants who experienced adverse effect during treatment phase.

Secondary Outcome Measures

The Percentage of Participants With Sputum Culture Conversion
Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multidrug-resistant tuberculosis (MDR-TB) taken at least 25 days apart.
The Median Time to Sputum Culture Conversion
Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multidrug-resistant tuberculosis (MDR-TB) taken at least 25 days apart.

Full Information

First Posted
June 1, 2020
Last Updated
July 5, 2022
Sponsor
Beijing Chest Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04421495
Brief Title
Safety and Effectiveness of Delamanid-containing Regimen for MDR-TB Patients in China
Official Title
Safety and Effectiveness of Delamanid-containing Regimen for Treatment of Patients With Multidrug-resistant Tuberculosis in China
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 16, 2020 (Actual)
Primary Completion Date
June 16, 2022 (Actual)
Study Completion Date
July 16, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beijing Chest Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multidrug Resistant Tuberculosis
Keywords
safety, Delamanid, effectiveness

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
608 (Actual)

8. Arms, Groups, and Interventions

Arm Title
delamanid containing regimen arm
Arm Type
Experimental
Arm Description
the only one arm to be studied with delamid-containing regimen.
Intervention Type
Drug
Intervention Name(s)
Delamanid
Other Intervention Name(s)
anti-TB new drug containing regimen
Intervention Description
the eligible patients will be give damanid-containing regimen
Primary Outcome Measure Information:
Title
Proportion of participants experiencing all-cause mortality
Description
the percentage of participants who died during the trial.
Time Frame
from enrollment to the completion of the trial ,an average of 30-32months
Title
Proportion of participants experiencing treatment-emergent AEs
Description
the percentage of participants who experienced adverse effect during treatment phase.
Time Frame
the whole treatment phase,an average of 18-20 months
Secondary Outcome Measure Information:
Title
The Percentage of Participants With Sputum Culture Conversion
Description
Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multidrug-resistant tuberculosis (MDR-TB) taken at least 25 days apart.
Time Frame
up to 24 weeks after enrollment
Title
The Median Time to Sputum Culture Conversion
Description
Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multidrug-resistant tuberculosis (MDR-TB) taken at least 25 days apart.
Time Frame
upto 24 weeks after enrollment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with microbiologically confirmed multidrug-resistant/rifampicin resistant tuberculosis ; Age 18 to 65 years old; MDR-TB treatment has not been started, or treatment has been started but treatment regimen need to be intensified; According to the guidelines of WHO's consolidated guidelines for the treatment of drug-resistant TB and the consensus of Chinese experts in the treatment of multidrug-resistant and rifampicin resistant TB (2019 edition), effective treatment regimens can only be formed by adding Delamanid based on the results of drug susceptibility testing and the previous treatment history; No history of respiratory failure, no history of cardiac dysfunction and clinically significant arrhythmia, QTcF < 450ms; Patients should be able to take medicines and clinical monitoring according to the requirements of the trial during the treatment and follow-up phases, and adverse effects should be reported to the responsible doctor timely ; Patients should sign the informed consent. Exclusion Criteria: A history of allergy to nitroimidazole and pyrrole drugs such as Delamanid, metronidazole, tinidazole, or any excipient. Serum transaminase increased ≥3 times the upper limit of normal value or total bilirubin increased ≥2.5 times the upper limit of normal, serum albumin <2.8 g / dL, severe renal impairment. Taking strong CYP3A4 inducer drugs (such as carbamazepine). Is known to be pregnant (or planning to become pregnant) . Participants took part in trials of other new unlisted drugs within the past three months; Congenital QT interval prolongation is known or has any disease that may prolong the QT interval or QTc no less than 500 ms; A history of symptomatic arrhythmia or suffering from clinically related bradycardia; Any cardiac disease that can induce arrhythmias, such as severe hypertension, left ventricular hypertrophy (including hypertrophic cardiomyopathy), or congestive heart failure with reduced left ventricular ejection fraction; Electrolyte disturbance, especially hypokalemia, hypocalcemia or hypomagnesemia; Taking drugs known to prolong the QT interval such as the following drugs (but not limited to) : ① Anti-arrhythmic drugs, such as amiodarone, disopyramide, dofetilide, ibutilide, procainamide, quinidine, hydroquinidine, sotalol, etc .; Antipsychotic drugs, such as phenothiazine, sertindole, sultopride, chlorpromazine, haloperidol, mesoridazine, pimozide or thioridazine, and antidepressants; ③ Certain antibiotics, including: Macrolides, such as erythromycin, clarithromycin, etc ; Moxifloxacin, Sparfloxacin; Triazole antifungal drugs; Spray him with amidine; Saquinavir; ④ Some non-sedative antihistamines, such as terfenadine, astemizole, mizolastine, etc. Other drugs with protential cardiac risk : cisapride, haloperidol, domperidone, bepridil, diphemanil, probucol, dimepheptanol, methadone, vinblastine, arsenic trioxide. Deletion criteria: Those who are found to have exclusion items after enrolled; Serious adverse reactions caused by Delamanid, such as allergic reactions, mental disorders, and liver injury (transaminases increase greater than 3 times the upper limit of normal value or total bilirubin increase greater than 2.5 times the upper limit of normal); QTcF ≥500ms or clinically significant ventricular arrhythmia is confirmed; The expert group made decision that it is not appropriate for the patient to continue the treatment with Delamanid; The patient cannot tolerate the background treatment regimen, or the modified background treatment regimen cannot meet the 3 definitive sensitive drugs or 4 probably sensitive drugs; The patient requests dropout.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Liang Li
Organizational Affiliation
Beijing Chest Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Chest Hospital, Capital Medical University
City
Beijing
ZIP/Postal Code
101149
Country
China
Facility Name
Changsha Central Hospital
City
Changsha
Country
China
Facility Name
Public Health Clinical Center of Chengdu
City
Chengdu
Country
China
Facility Name
Chongqing Infectious Disease Medical Center
City
Chongqing
Country
China
Facility Name
Fuzhou Pulmonary Hospital of Fujian
City
Fuzhou
Country
China
Facility Name
Guangzhou Chest Hospital
City
Guangzhou
Country
China
Facility Name
Guiyang Public Health Clinical Center
City
Guiyang
Country
China
Facility Name
Heilongjiang Province center for tuberculosis Control and Prevention
City
Haerbin
Country
China
Facility Name
Hangzhou Red Cross Hospital
City
Hangzhou
Country
China
Facility Name
Jiamusi Tumor Hospital
City
Jiamusi
Country
China
Facility Name
Tuberculosis Hospital in Jilin Province
City
Jilin
Country
China
Facility Name
Shandong Provincial Chest Hospital
City
Jinan
Country
China
Facility Name
The Third People's Hospital of Kunming City
City
Kunming
Country
China
Facility Name
Lanzhou Pulmonary Hospital
City
Lanzhou
Country
China
Facility Name
Longtan Hospital of Guangxi Zhuang Autonomous Region
City
Liuzhou
Country
China
Facility Name
Jiangxi Chest (Third People) Hospital
City
Nanchang
Country
China
Facility Name
Shanghai Pulmonary Hospital
City
Shanghai
Country
China
Facility Name
Hebei Chest Hospital
City
Shijiangzhuang
Country
China
Facility Name
The Fifth People Hospital of Suzhou
City
Suzhou
Country
China
Facility Name
The Fourth People's Hospital of Taiyuan
City
Taiyuan
Country
China
Facility Name
Wuhan Institute For Tuberculosis Control
City
Wuhan
Country
China
Facility Name
Wuhan Jinyintan Hospital
City
Wuhan
Country
China
Facility Name
Xi'an Chest Hospital
City
Xi'an
Country
China
Facility Name
Shanxi Provincial Tuberculosis Institute
City
Xian
Country
China
Facility Name
Henan Provincial Chest Hospital
City
Zhengzhou
Country
China

12. IPD Sharing Statement

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Safety and Effectiveness of Delamanid-containing Regimen for MDR-TB Patients in China

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