Back to resultsA Study of an Oral Short-course Regimen Including Bedaquiline for the Treatment of Participants With Multidrug-resistant Tuberculosis in China (PROSPECT)
Primary Purpose
Tuberculosis, Multidrug-Resistant
Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Bedaquiline
Levofloxacin
Linezolid
Cycloserine
Clofazimine
Pyrazinamide
Protionamide
Sponsored by
About this trial
This is an interventional treatment trial for Tuberculosis, Multidrug-Resistant
Eligibility Criteria
Inclusion Criteria:
- Has a positive sputum Mycobacterium tuberculosis culture from a test performed at screening
- Has microbiological confirmation of rifampicin resistance by GeneXpert and to isoniazid (INH) via molecular drug-susceptibility testing (DST) showing katG mutation
- Has a chest imaging result compatible with a diagnosis of pulmonary Tuberculosis (TB)
- Agrees to use effective contraception during the 40-week study treatment phase. A female participant must be: of nonchildbearing potential; of childbearing potential and practicing effective methods of contraception during the 40-week study treatment phase
- Is willing to undergo human immunodeficiency virus (HIV) testing
Exclusion Criteria:
- Has received prior treatment with bedaquiline
- Has prior exposure to at least 1 second-line drug in the regimen for at least 4 weeks
- Has any grade 3 or 4 laboratory abnormality as confirmed by a clinical expert
- Has a known allergy or intolerance to bedaquiline or other drugs in the regimen
- Is infected with a strain of nontuberculous mycobacteria
- Is HIV-positive
Sites / Locations
- Beijing Chest HospitalRecruiting
- The Eighth Medical Center of PLA General HospitalRecruiting
- Changsha Central HospitalRecruiting
- Public health clinical medical center of ChengduRecruiting
- Chongqing Public Health Medical CenterRecruiting
- The Pulmonary Hospital of Fuzhou in Fujian Province（The tuberculosis control and prevention Hospital of Fuzhou in Fujian Province）Recruiting
- Guiyang Public Health Clinical CenterRecruiting
- Anhui Chest HospitalRecruiting
- Infectious Disease Hospital of Heilongjiang ProvinceRecruiting
- Jiamusi Tumor Hospital
- Jiangxi Chest Hospital
- Shandong public health clinical centerRecruiting
- Shanghai Pulmonary HospitalRecruiting
- Shenyang Chest HospitalRecruiting
- Wuhan Pulmonary HospitalRecruiting
- Xi'an Chest HospitalRecruiting
- The First Affiliated Hospital of Xinxiang Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Bedaquiline-containing Short-course Regimen (SCR)
Non-bedaquiline-containing Short-course Regimen (SCR)
Arm Description
Participants will receive an oral dose of bedaquiline 400 milligrams (mg) once daily for first 2 weeks followed by bedaquiline 200 mg thrice a week for 22 weeks (with at least 48 hours between doses) in combination with oral doses of levofloxacin (LFX) up to 1000 mg (weight-based), cycloserine (CS) up to 750 mg (weight-based), clofazimine (CFZ) 100 mg daily for 40 weeks and linezolid [LZD] 600 mg daily for at least 24 weeks . If a participant is still sputum culture-positive for Mycobacterium tuberculosis by Week 16, bedaquiline treatment will be extended from Week 24 to Week 40.
Participants will receive oral doses of LFX up to 1000 mg (weight-based), CS up to 750 mg (weight-based), CFZ 100 mg, Pyrazinamide (PZA) up to 2000 mg (weight-based), Protionamide (PTO) up to 800 mg (weight-based) daily for first 16 weeks and LZD 600 mg daily for at least 24 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants with a Favorable Treatment Outcome at the End of Treatment
Percentage of participants with a favorable treatment outcome at the end of treatment will be reported. A participant's outcome will be classified as favorable if their last 3 culture results by the end of treatment are negative unless they have previously been classified as unfavorable. These 3 cultures must be taken on separate visits; the latest of which being no more than 8 weeks prior to the end of treatment.
Secondary Outcome Measures
Percentage of Participants with a Favorable Treatment Outcome at 48 Weeks Post the End of Treatment
Percentage of participants with a favorable treatment outcome at 48 weeks post the end of treatment will be reported. A participant's outcome will be classified as favorable if their last 3 culture results by the end of treatment are negative unless they have previously been classified as unfavorable. These 3 cultures must be taken on separate visits; the latest of which being no more than 8 weeks prior to the end of treatment.
Percentage of Participants Achieving Treatment Success at the end of Treatment
Percentage of participants achieving treatment success at the end of treatment will be reported. Treatment success is achieved if participants completed their prescribed tuberculosis (TB) treatment; or if their last 3 culture results are negative by the end of treatment, these 3 cultures must be taken on separate visits and should be after the initial 6-month treatment period.
Percentage of Participants with a Modified Favorable Treatment Outcome at the end of Treatment and at 48 Weeks Post end of Treatment
Percentage of participants with a modified favorable treatment outcome at the end of treatment and at 48 weeks post end of treatment will be reported. A participant's treatment outcome will be classified as modified favorable if their last 2 culture results by the end of treatment are negative unless they have previously been classified as unfavorable. These 2 cultures must be taken on separate visits; the latest of which being no more than 8 weeks prior to the end of treatment.
Percentage of Participants Experiencing All-cause Mortality
Percentage of participants experiencing all-cause mortality will be reported.
Percentage of Participants Experiencing Grade 3 or Greater Treatment-emergent Adverse Events (TEAEs) During Study Treatment and Follow-up
Percentage of participants experiencing grade 3 or greater TEAEs during study treatment and follow-up will be reported. An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as any event that begins or worsens in severity after initiation of study drug through to the end of study. An assessment of severity grade will be made using the following 5 general categorical descriptors based on division of acquired immunodeficiency syndrome (AIDS) grading for AE severity assessment. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death.
Percentage of Participants Experiencing TEAEs
Percentage of participants experiencing TEAEs will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as any event that begins or worsens in severity after initiation of study drug through to the end of study.
Percentage of Participants with TB Relapses and Re-infections During the Treatment-free Follow-up Phase
Percentage of participants with TB relapses and re-infections during the treatment-free follow-up phase will be reported.
Percentage of Participants Whose Isolates Develop Resistance to Bedaquiline and Other Drugs Used in the Regimen
Percentage of participants whose isolates develop resistance to bedaquiline and other drugs used in the regimen will be reported.
Full Information
NCT ID
NCT05306223
First Posted
March 23, 2022
Last Updated
January 13, 2023
Sponsor
Beijing Chest Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05306223
Brief Title
A Study of an Oral Short-course Regimen Including Bedaquiline for the Treatment of Participants With Multidrug-resistant Tuberculosis in China
Acronym
PROSPECT
Official Title
A Pragmatic Randomized Controlled Trial to Evaluate the Efficacy and Safety of an Oral Short-course Regimen Including Bedaquiline for the Treatment of Patients With Multidrug-resistant Tuberculosis in China
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 10, 2022 (Actual)
Primary Completion Date
August 8, 2025 (Anticipated)
Study Completion Date
August 8, 2025 (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
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate efficacy and safety of an oral bedaquiline-containing multidrug-resistant tuberculosis (MDR-TB) short-course regimen (SCR) compared to an oral SCR not including bedaquiline at the end of treatment in participants with pulmonary MDR-TB in China.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, Multidrug-Resistant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
212 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Bedaquiline-containing Short-course Regimen (SCR)
Arm Type
Experimental
Arm Description
Participants will receive an oral dose of bedaquiline 400 milligrams (mg) once daily for first 2 weeks followed by bedaquiline 200 mg thrice a week for 22 weeks (with at least 48 hours between doses) in combination with oral doses of levofloxacin (LFX) up to 1000 mg (weight-based), cycloserine (CS) up to 750 mg (weight-based), clofazimine (CFZ) 100 mg daily for 40 weeks and linezolid [LZD] 600 mg daily for at least 24 weeks . If a participant is still sputum culture-positive for Mycobacterium tuberculosis by Week 16, bedaquiline treatment will be extended from Week 24 to Week 40.
Arm Title
Non-bedaquiline-containing Short-course Regimen (SCR)
Arm Type
Experimental
Arm Description
Participants will receive oral doses of LFX up to 1000 mg (weight-based), CS up to 750 mg (weight-based), CFZ 100 mg, Pyrazinamide (PZA) up to 2000 mg (weight-based), Protionamide (PTO) up to 800 mg (weight-based) daily for first 16 weeks and LZD 600 mg daily for at least 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Bedaquiline
Other Intervention Name(s)
SIRTURO
Intervention Description
Bedaquiline uncoated tablets will be administered orally.
Intervention Type
Drug
Intervention Name(s)
Levofloxacin
Intervention Description
Levofloxacin filmcoated will be administered orally
Intervention Type
Drug
Intervention Name(s)
Linezolid
Intervention Description
Linezolid tablets will be administered orally
Intervention Type
Drug
Intervention Name(s)
Cycloserine
Intervention Description
Cycloserine capsules will be administered orally.
Intervention Type
Drug
Intervention Name(s)
Clofazimine
Intervention Description
Clofazimine capsules will be administered orally.
Intervention Type
Drug
Intervention Name(s)
Pyrazinamide
Intervention Description
Pyrazinamide tablets will be administered orally.
Intervention Type
Drug
Intervention Name(s)
Protionamide
Intervention Description
Protionamide enteric-coated tablets will be administered orally.
Primary Outcome Measure Information:
Title
Percentage of Participants with a Favorable Treatment Outcome at the End of Treatment
Description
Percentage of participants with a favorable treatment outcome at the end of treatment will be reported. A participant's outcome will be classified as favorable if their last 3 culture results by the end of treatment are negative unless they have previously been classified as unfavorable. These 3 cultures must be taken on separate visits; the latest of which being no more than 8 weeks prior to the end of treatment.
Time Frame
At the end of treatment (Week 40)
Secondary Outcome Measure Information:
Title
Percentage of Participants with a Favorable Treatment Outcome at 48 Weeks Post the End of Treatment
Description
Percentage of participants with a favorable treatment outcome at 48 weeks post the end of treatment will be reported. A participant's outcome will be classified as favorable if their last 3 culture results by the end of treatment are negative unless they have previously been classified as unfavorable. These 3 cultures must be taken on separate visits; the latest of which being no more than 8 weeks prior to the end of treatment.
Time Frame
At 48 weeks post the end of treatment (Week 88)
Title
Percentage of Participants Achieving Treatment Success at the end of Treatment
Description
Percentage of participants achieving treatment success at the end of treatment will be reported. Treatment success is achieved if participants completed their prescribed tuberculosis (TB) treatment; or if their last 3 culture results are negative by the end of treatment, these 3 cultures must be taken on separate visits and should be after the initial 6-month treatment period.
Time Frame
At the end of treatment (Week 40)
Title
Percentage of Participants with a Modified Favorable Treatment Outcome at the end of Treatment and at 48 Weeks Post end of Treatment
Description
Percentage of participants with a modified favorable treatment outcome at the end of treatment and at 48 weeks post end of treatment will be reported. A participant's treatment outcome will be classified as modified favorable if their last 2 culture results by the end of treatment are negative unless they have previously been classified as unfavorable. These 2 cultures must be taken on separate visits; the latest of which being no more than 8 weeks prior to the end of treatment.
Time Frame
At the end of treatment (Week 40) and at 48 weeks post end of treatment (Week 88)
Title
Percentage of Participants Experiencing All-cause Mortality
Description
Percentage of participants experiencing all-cause mortality will be reported.
Time Frame
Up to Week 88
Title
Percentage of Participants Experiencing Grade 3 or Greater Treatment-emergent Adverse Events (TEAEs) During Study Treatment and Follow-up
Description
Percentage of participants experiencing grade 3 or greater TEAEs during study treatment and follow-up will be reported. An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as any event that begins or worsens in severity after initiation of study drug through to the end of study. An assessment of severity grade will be made using the following 5 general categorical descriptors based on division of acquired immunodeficiency syndrome (AIDS) grading for AE severity assessment. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death.
Time Frame
During study treatment and follow-up (From Week 1 up to Week 88)
Title
Percentage of Participants Experiencing TEAEs
Description
Percentage of participants experiencing TEAEs will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as any event that begins or worsens in severity after initiation of study drug through to the end of study.
Time Frame
From Week 1 up to Week 88
Title
Percentage of Participants with TB Relapses and Re-infections During the Treatment-free Follow-up Phase
Description
Percentage of participants with TB relapses and re-infections during the treatment-free follow-up phase will be reported.
Time Frame
During the treatment-free follow-up phase (Up to 48 weeks)
Title
Percentage of Participants Whose Isolates Develop Resistance to Bedaquiline and Other Drugs Used in the Regimen
Description
Percentage of participants whose isolates develop resistance to bedaquiline and other drugs used in the regimen will be reported.
Time Frame
Up to Week 88
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:
Has a positive sputum Mycobacterium tuberculosis culture from a test performed at screening
Has microbiological confirmation of rifampicin resistance by GeneXpert and to isoniazid (INH) via molecular drug-susceptibility testing (DST) showing katG mutation
Has a chest imaging result compatible with a diagnosis of pulmonary Tuberculosis (TB)
Agrees to use effective contraception during the 40-week study treatment phase. A female participant must be: of nonchildbearing potential; of childbearing potential and practicing effective methods of contraception during the 40-week study treatment phase
Is willing to undergo human immunodeficiency virus (HIV) testing
Exclusion Criteria:
Has received prior treatment with bedaquiline
Has prior exposure to at least 1 second-line drug in the regimen for at least 4 weeks
Has any grade 3 or 4 laboratory abnormality as confirmed by a clinical expert
Has a known allergy or intolerance to bedaquiline or other drugs in the regimen
Is infected with a strain of nontuberculous mycobacteria
Is HIV-positive
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jingtao Gao, PhD
Phone
+8610-89509131
Email
jingtaogao@outlook.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mengqiu Gao
Organizational Affiliation
Beijing Chest Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Chest Hospital
City
Beijing
ZIP/Postal Code
101149
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mengqiu Gao
Facility Name
The Eighth Medical Center of PLA General Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Huiru An
Facility Name
Changsha Central Hospital
City
Changsha
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yi Pei
Facility Name
Public health clinical medical center of Chengdu
City
Chengdu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guihui Wu
Facility Name
Chongqing Public Health Medical Center
City
Chongqing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaofeng Yan
Facility Name
The Pulmonary Hospital of Fuzhou in Fujian Province（The tuberculosis control and prevention Hospital of Fuzhou in Fujian Province）
City
Fuzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaohong Chen
Facility Name
Guiyang Public Health Clinical Center
City
Guiyang
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhongfeng Huang
Facility Name
Anhui Chest Hospital
City
Hefei
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hua Wang
Facility Name
Infectious Disease Hospital of Heilongjiang Province
City
Heilongjiang
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Long Jin
Facility Name
Jiamusi Tumor Hospital
City
Jiamusi
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiujie Li
Facility Name
Jiangxi Chest Hospital
City
Jiangxi
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuqing Wu
Facility Name
Shandong public health clinical center
City
Shandong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yu Xiong
Facility Name
Shanghai Pulmonary Hospital
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei Sha
Facility Name
Shenyang Chest Hospital
City
Shenyang
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lian Shi
Facility Name
Wuhan Pulmonary Hospital
City
Wuhan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan Du
Facility Name
Xi'an Chest Hospital
City
Xi'an
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fei Ren
Facility Name
The First Affiliated Hospital of Xinxiang Medical University
City
Xinxiang
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Junwei Cui
12. IPD Sharing Statement
Learn more about this trial
A Study of an Oral Short-course Regimen Including Bedaquiline for the Treatment of Participants With Multidrug-resistant Tuberculosis in China
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