Tuberculosis, PulmonaryPhase 3ESCAPE-TBNCT04856644
Evaluation of the Efficacy and Safety of a 4-month Daily Regimen (2HZPM/2HPM) for Treatment of Pulmonary TB
A Phase 3 study testing 4-month rifapentine-based regimen in people with Tuberculosis, Pulmonary, run by Kaohsiung Veterans General Hospital. at 4 sites in Taiwan.
Trial summary
The development of efficacious, safe, and shorter treatment regimens could significantly improve TB management and treatment success rates. This prospective, 3-year, single arm study is to evaluate the efficacy and safety of a short-course, 4-month regimen including isoniazid(H), pyrazinamide(P), rifapentine (P), and… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Tuberculosis, Pulmonary
- What is being tested?
- 4-month rifapentine-based regimen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 333 participants
- Where
- 4 sitesTaiwan
- Study dates
- 1 Jan 2020to 31 Dec 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Suspected newly diagnosed pulmonary TB plus one of the following: a) at least one sputum specimen positive for acid-fast bacilli on smear microscopy OR b) at least one sputum specimen positive for Mycobacterium tuberculosis by culture or "Gene Xpert MTB/RIF" testing, with rifamycin resistance not detected, OR c) histopathologic findings compatible with mycobacterial infection including a positive acid-fast stain
- Patient with a history of being untreated for 3 years after cure from a previous episode of TB can be included.
- Age 20 years or older
- For women of childbearing potential, a negative pregnancy test at or within seven (7) days prior to screening is required, and must agree to practice a barrier method of contraception during study drug treatment, or be surgically sterilized or have an intrauterine contraceptive device in place.
- Laboratory parameters performed at or within 14 days prior to enrollment:
- Serum or plasma alanine aminotransferase (ALT) less than or equal to 3 times the upper limit of normal
Show all 12Show fewer
- Serum or plasma total bilirubin less than or equal to 2.5 times the upper limit of normal
- Serum or plasma creatinine level less than or equal to 2 times the upper limit of normal or Creatinine clearance (CrCl) level greater than 30 mL/min.
- Serum or plasma potassium level greater than or equal to 3.5 milliequivalent/L
- Hemoglobin level of 7.0 g/dL or greater
- Platelet count of 100,000/mm3 or greater
- Patient signed a written informed consent
Who cannot join
- Pregnant or breast-feeding.
- Unable to take oral medications.
- Previously enrolled in this study.
- Received any investigational drug in the past 3 months.
- More than 14 days of systemic treatment with any antituberculous drugs preceding initiation of study drugs.
- Known history of prolonged QT syndrome.
Show all 12Show fewer
- Suspected or documented TB involving the central nervous system and/or bones and/or joints, and/or miliary tuberculosis and/or pericardial tuberculosis.
- Weight less than 40.0 kg.
- Known allergy or intolerance to any of the study medications.
- Individuals will be excluded from enrollment if, at the time of enrollment, their M. tuberculosis isolate is already known to be resistant to any one or more of the following: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones.
- Medical conditions, including HIV infection and others conditions that, in the investigator's judgment, make study participation not in the individual's best interest.
- Late exclusions: Drug-resistant TB by either rapid sputum based test (Gene Expert) or resistance testing using an indirect susceptibility test in liquid culture to isoniazid, rifampin, ethambutol, pyrazinamide or resistance to moxifloxacin or rifapentine by microdilution agar proportion test.
Trial locations and contacts
4 sites in 1 country.
Taiwan4 sites
Kaohsiung Veterans General Hospital
Kaohsiung City, 813
Taipei Veterans General Hospital
Taipei, 112
National Taiwan University Hospital
Taipei
Linkou Chang Gung Memorial Hospital
Taoyuan City, 333
About this study
Official title: Evaluation of the Efficacy and Safety of a Short-course, Daily, 4-month Regimen Including Isoniazid, Pyrazinamide, Rifapentine and Moxifloxacin (2HZPM/2HPM) for the Treatment of Drug-susceptible Pulmonary Tuberculosis in Taiwan (ESCAPE-TB)
The development of efficacious, safe, and shorter treatment regimens could significantly improve TB management and treatment success rates. This prospective, 3-year, single arm study is to evaluate the efficacy and safety of a short-course, 4-month regimen including isoniazid(H), pyrazinamide(P), rifapentine (P), and moxifloxacin(M) (2HZPM/2HPM) for the treatment of drug-susceptible, pulmonary tuberculosis, and compared with a historical control group receiving the standard six-month regimen.
Read the detailed description
Shorter regimens have the potential to impact on TB control by reducing TB incidence and mortality, and improve outcomes by increasing patient adherence to treatments and decreasing duration to cure, in addition to reducing costs to the health system and the patient. The purpose of this prospective, three year, single arm study is to evaluate whether a short course, four-month regimen containing rifapentine and moxifloxacin (2HZPM/2HPM) are as effective and/or as tolerable as the standard six-month regimen for the treatment of drug-susceptible, pulmonary tuberculosis (TB). A historical group receiving the standard six-month regimen is used as control at a ratio of 1:2. The pharmacokinetic and pharmacodynamic profile of rifapentine in Asian patients. Analysis of of histocompatibility leucocyte antigen (HLA) associations with adverse events and changes in biomarkers will be done.
- Conditions
- Tuberculosis, Pulmonary
- Being tested
- 4-month rifapentine-based regimen
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4-month rifapentine-based regimenDrug
Also called rifapentine, moxifloxacin, priftin
8 weeks of isoniazid, pyrazinamide, rifapentine, and moxifloxacin, followed by 9 weeks of isoniazid, rifapentine and moxifloxacin
| Study group | Role | What they receive |
|---|---|---|
| 4-month regimen (2HZPM/2HPM) | Experimental | * Eight weeks of daily treatment with isoniazid (H), pyrazinamide (Z), rifapentine (P), and moxifloxacin (M), followed by
* Nine weeks of daily treatment with isoniazid, rifapentine and moxifloxacin Receives: Drug: 4-month rifapentine-based regimen |
| Standard 6-month regimen (2HERZ/4HR) historical control | No intervention | a standard, six-month regimen, with * Eight weeks of daily treatment with isoniazid (H), rifampin (R), pyrazinamide (Z) and ethambutol (E) followed by * Eighteen weeks of daily treatment with isoniazid and rifampin, with or without ethambutol |
What is being measured
The primary outcome is the main question the study is designed to answer.
TB disease free survival at 12 months
Number and follow up time of participants without TB disease at 12 months after study treatment assignment in person-months
Measured: 12 months after study treatment assignment
Grade 3 or higher adverse events during study drug treatment
The number of participants with grade 3 or higher adverse events during study drug treatment divided by total number of participants
Measured: 0-4 months
Secondary outcomes (14)
Early sterilizing activity (Negative sputum cultures at end of intensive 8 weeks phase)
The number of patients with a negative sputum culture at the end of intensive phase therapy at 8 weeks divided by total number of participants
Measured: 8 weeks
Time to stable sputum conversion (Time in days from conversion of a positive sputum culture to negative sputum culture)
Number of days from start of treatment to first negative sputum culture that remain negative thereafter
Measured: 4, 8, 12, 17 weeks, 6 months, 12 months
Speed of decline of sputum viable bacilli by automated mycobacteria growth indicator tube (MGIT) days to detection
Number of days from loading of sputum culture into MGIT to the day of detection of viable mycobacteria
Measured: 2-8 weeks
TB disease-free survival at 12 months after study treatment assignment assuming all losses to follow-up and non-TB deaths have an unfavorable outcome (Sensitivity analyses assuming all losses to follow-up and non-TB deaths have an unfavorable outcome)
Number and follow up time of participants without TB disease at 12 months after study treatment assignment assuming all losses to follow-up and non-TB deaths have an unfavorable outcome (Sensitivity analyses assuming all losses to follow-up and non-TB deaths have an unfavorable outcome) in person-months
Measured: 12 months
TB disease-free survival at 12 months after study treatment assignment assuming all losses to follow-up and non-TB deaths have an favorable outcome (Sensitivity analyses assuming all losses to follow-up and non-TB deaths have an favorable outcome)
Number and follow up time of participants without TB disease at 12 months after study treatment assignment assuming all losses to follow-up and non-TB deaths have an favorable outcome (Sensitivity analyses assuming all losses to follow-up and non-TB deaths have an favorable outcome) in person-months
Measured: 12 months
Rates of treatment discontinuation for reasons other than ineligibility (late exclusions due to drug resistance or HIV status)
Number of participants who discontinued treatment for reasons other than ineligibility (late exclusions due to drug resistance or HIV status) divided by total number of participants
Measured: 0-4 months
All-cause mortality at 4 months post-treatment assignment
Number of participants who died at 4 months divided by number of participants
Measured: 4 months
All-cause mortality at 12 months post-treatment assignment
Number of participants who died at 12 months divided by number of participants
Measured: 12 months
Attributable mortality at 4 months post-treatment assignment
Number of patients who died due to reasons attributable to tuberculosis at 4 months post-treatment assignment divided by number of participants
Measured: 4 months
Attributable mortality at 12 months post-treatment assignment
Number of patients who died due to reasons attributable to tuberculosis at 12 months post-treatment assignment divided by number of participants
Measured: 12 months
Changes in interferon-gamma levels during treatment compared to baseline
interferon-gamma levels during treatment minus baseline levels
Measured: 2, 4, 8, 12 weeks
Changes in tumor necrosis factor-alpha levels during treatment compared to baseline
Tumor necrosis factor-alpha levels during treatment minus baseline levels
Measured: 2, 4, 8, 12 weeks
Changes in interleukin-12 and interleukin-6 levels during treatment compared to baseline
Interleukin-12 levels during treatment minus baseline levels
Measured: 2, 4, 8, 12 weeks
Changes in triggering receptor expressed on myeloid cells-1 (TREM-1) levels during treatment compared to baseline
Triggering receptor expressed on myeloid cells-1 (TREM-1) levels during treatment minus baseline levels
Measured: 2, 4, 8, 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2021
- Study start1 Jan 2020
- Primary completion31 Dec 2023
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculosis, PulmonaryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The intervention group: all patients recruited into the study will receive the 4-month regimen The comparator group: historical control in those who received the standard 6-month regimen
- Masking
- None (open label)
- Enrolment
- 333 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kaohsiung Veterans General Hospital.
- Sponsor type
- University, hospital or other
- Collaborators
- National Taiwan University, Taipei Veterans General Hospital, Taiwan, Chang Gung Memorial Hospital, Centers for Disease Control, Taiwan
- Responsible party
- Principal investigator, Susan Shin-Jung Lee, Kaohsiung Veterans General Hospital.
- Investigators
- Susan Shin-Jung Lee, M.D., Ph.D., Principal investigator, Kaohsiung Veterans General Hospital.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04856644
- Sponsor's protocol ID
- KSVGH21-CT5-49
- Acronym
- ESCAPE-TB
- Status last verified
- Jul 2024
- First submitted
- 31 Mar 2021
- Last updated
- 12 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Efficacy and Safety of a Short-course, Daily, 4-month Regimen Including Isoniazid, Pyrazinamide, Rifapentine and Moxifloxacin (2HZPM/2HPM) for the Treatment of Drug-susceptible Pulmonary Tuberculosis in Taiwan (ESCAPE-TB)
- ClinicalTrials.gov ID
- NCT04856644
- Acronym / sponsor ID
- ESCAPE-TB / KSVGH21-CT5-49
- Conditions
- Tuberculosis, Pulmonary
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 333 participants (actual)
- Lead sponsor
- Kaohsiung Veterans General Hospital.University, hospital or other
- Collaborators
- National Taiwan University, Taipei Veterans General Hospital, Taiwan, Chang Gung Memorial Hospital, Centers for Disease Control, Taiwan
- Study start
- 1 Jan 2020 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 23 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The development of efficacious, safe, and shorter treatment regimens could significantly improve TB management and treatment success rates. This prospective, 3-year, single arm study is to evaluate the efficacy and safety of a short-course, 4-month regimen including isoniazid(H), pyrazinamide(P), rifapentine (P), and moxifloxacin(M) (2HZPM/2HPM) for the treatment of drug-susceptible, pulmonary tuberculosis, and compared with a historical control group receiving the standard six-month regimen.
Detailed description
Shorter regimens have the potential to impact on TB control by reducing TB incidence and mortality, and improve outcomes by increasing patient adherence to treatments and decreasing duration to cure, in addition to reducing costs to the health system and the patient. The purpose of this prospective, three year, single arm study is to evaluate whether a short course, four-month regimen containing rifapentine and moxifloxacin (2HZPM/2HPM) are as effective and/or as tolerable as the standard six-month regimen for the treatment of drug-susceptible, pulmonary tuberculosis (TB). A historical group receiving the standard six-month regimen is used as control at a ratio of 1:2. The pharmacokinetic and pharmacodynamic profile of rifapentine in Asian patients. Analysis of of histocompatibility leucocyte antigen (HLA) associations with adverse events and changes in biomarkers will be done.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The intervention group: all patients recruited into the study will receive the 4-month regimen The comparator group: historical control in those who received the standard 6-month regimen
| Arm | Type | Receives |
|---|---|---|
| 4-month regimen (2HZPM/2HPM) | Experimental | Drug: 4-month rifapentine-based regimen* Eight weeks of daily treatment with isoniazid (H), pyrazinamide (Z), rifapentine (P), and moxifloxacin (M), followed by * Nine weeks of daily treatment with isoniazid, rifapentine and moxifloxacin |
| Standard 6-month regimen (2HERZ/4HR) historical control | No intervention | –a standard, six-month regimen, with * Eight weeks of daily treatment with isoniazid (H), rifampin (R), pyrazinamide (Z) and ethambutol (E) followed by * Eighteen weeks of daily treatment with isoniazid and rifampin, with or without ethambutol |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Suspected newly diagnosed pulmonary TB plus one of the following: a) at least one sputum specimen positive for acid-fast bacilli on smear microscopy OR b) at least one sputum specimen positive for Mycobacterium tuberculosis by culture or "Gene Xpert MTB/RIF" testing, with rifamycin resistance not detected, OR c) histopathologic findings compatible with mycobacterial infection including a positive acid-fast stain
- Patient with a history of being untreated for 3 years after cure from a previous episode of TB can be included.
- Age 20 years or older
- For women of childbearing potential, a negative pregnancy test at or within seven (7) days prior to screening is required, and must agree to practice a barrier method of contraception during study drug treatment, or be surgically sterilized or have an intrauterine contraceptive device in place.
- Laboratory parameters performed at or within 14 days prior to enrollment:
Key exclusion criteria (12 listed)
- Pregnant or breast-feeding.
- Unable to take oral medications.
- Previously enrolled in this study.
- Received any investigational drug in the past 3 months.
- More than 14 days of systemic treatment with any antituberculous drugs preceding initiation of study drugs.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 4-month rifapentine-based regimenAlso: rifapentine, moxifloxacin, priftin8 weeks of isoniazid, pyrazinamide, rifapentine, and moxifloxacin, followed by 9 weeks of isoniazid, rifapentine and moxifloxacin | Drug | 4-month regimen (2HZPM/2HPM) |
Primary outcome
TB disease free survival at 12 months
Time frame: 12 months after study treatment assignment
Number and follow up time of participants without TB disease at 12 months after study treatment assignment in person-months
Grade 3 or higher adverse events during study drug treatment
Time frame: 0-4 months
The number of participants with grade 3 or higher adverse events during study drug treatment divided by total number of participants
14 secondary outcomes
Early sterilizing activity (Negative sputum cultures at end of intensive 8 weeks phase)
Time frame: 8 weeks
Time to stable sputum conversion (Time in days from conversion of a positive sputum culture to negative sputum culture)
Time frame: 4, 8, 12, 17 weeks, 6 months, 12 months
Speed of decline of sputum viable bacilli by automated mycobacteria growth indicator tube (MGIT) days to detection
Time frame: 2-8 weeks
TB disease-free survival at 12 months after study treatment assignment assuming all losses to follow-up and non-TB deaths have an unfavorable outcome (Sensitivity analyses assuming all losses to follow-up and non-TB deaths have an unfavorable outcome)
Time frame: 12 months
TB disease-free survival at 12 months after study treatment assignment assuming all losses to follow-up and non-TB deaths have an favorable outcome (Sensitivity analyses assuming all losses to follow-up and non-TB deaths have an favorable outcome)
Time frame: 12 months
Rates of treatment discontinuation for reasons other than ineligibility (late exclusions due to drug resistance or HIV status)
Time frame: 0-4 months
All-cause mortality at 4 months post-treatment assignment
Time frame: 4 months
All-cause mortality at 12 months post-treatment assignment
Time frame: 12 months
Attributable mortality at 4 months post-treatment assignment
Time frame: 4 months
Attributable mortality at 12 months post-treatment assignment
Time frame: 12 months
Changes in interferon-gamma levels during treatment compared to baseline
Time frame: 2, 4, 8, 12 weeks
Changes in tumor necrosis factor-alpha levels during treatment compared to baseline
Time frame: 2, 4, 8, 12 weeks
Changes in interleukin-12 and interleukin-6 levels during treatment compared to baseline
Time frame: 2, 4, 8, 12 weeks
Changes in triggering receptor expressed on myeloid cells-1 (TREM-1) levels during treatment compared to baseline
Time frame: 2, 4, 8, 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2024.
- Individual participant dataSharing planned: Undecided
Related trials for Tuberculosis, Pulmonary
RecruitingPhase 4
Short-term Antibiotic Therapy in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
Active, not recruitingObservational study
Mycobacterial and Opportunistic Infections in HIV-Negative Thai and Taiwanese Patients Associated With Autoantibodies to Interferon-gamma
Nontuberculous Mycobacteria, Mycobacterium Tuberculosis
RecruitingPhase 2
BRIGHT-Child TB: Short-Course Treatment for Non-Severe Pulmonary Tuberculosis in Children
Tuberculosis
RecruitingPhase 3
A Study of Quabodepistat-containing Regimens for the Treatment of Drug-resistant Pulmonary Tuberculosis
Rifampicin-Resistant Pulmonary Tuberculosis, Multidrug-Resistant Pulmonary Tuberculosis
Recruiting
Channa Striata and Curcuma Domestica Supplementation in Patients With Active Pulmonary Tuberculosis
Pulmonary Tuberculosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan Shin-Jung Lee, M.D., Ph.D. principal investigator
Kaohsiung Veterans General Hospital.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 4-month rifapentine-based regimen in people with Tuberculosis, Pulmonary, run by Kaohsiung Veterans General Hospital. at 4 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TB disease free survival at 12 months (time frame: 12 months after study treatment assignment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2024.