- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04856644
Evaluation of the Efficacy and Safety of a 4-month Daily Regimen (2HZPM/2HPM) for Treatment of Pulmonary TB (ESCAPE-TB)
April 22, 2021 updated by: Susan Shin-Jung Lee, Kaohsiung Veterans General Hospital.
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.
Study Overview
Status
Not yet recruiting
Conditions
Intervention / Treatment
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.
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 Type
Interventional
Enrollment (Anticipated)
366
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Susan Shin-Jung Lee, M.D., Ph.D.
- Phone Number: 2029 +886-7342-2121
- Email: ssjlee28@yahoo.com.tw
Study Contact Backup
- Name: Hsin-Wei Tung, R.N.
- Phone Number: 2062 +886-7342-2121
Study Locations
-
-
-
Kaohsiung, Taiwan, 813
- Kaohsiung Veterans General Hospital
-
Contact:
- Susan Shin-Jung Lee, M.D., Ph.D.
- Phone Number: 2029 +886-7342-2121
- Email: ssjlee28@yahoo.com.tw
-
Contact:
- Hsin-Wei Tung, R.N.
- Phone Number: 2062 +886-73422121
-
Sub-Investigator:
- Ya-Wei Weng, M.D.
-
Sub-Investigator:
- Chih-Chen Chou, M.D.
-
Sub-Investigator:
- Huan-Yi Wu, M.D.
-
Taipei, Taiwan
- National Taiwan University Hospital
-
Contact:
- Chin-Chung Shu, M.D.
- Phone Number: 65132 +886-2312-3456
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Taipei, Taiwan, 112
- Taipei Veterans General Hospital
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Contact:
- Jia-Yih Feng, M.D.
- Phone Number: 7564 +886-2871-2121
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Principal Investigator:
- Jia-Yih Feng, M.D.
-
Sub-Investigator:
- Sheng-Wei Pan, M.D.
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Taoyuan City, Taiwan, 333
- Linkou Chang Gung Memorial Hospital
-
Contact:
- Tsai-Yu Wang, M.D.
- Phone Number: 8470 +886-3-3281200
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Principal Investigator:
- Tsai-Yu Wang, M.D.
-
Sub-Investigator:
- Chung-Shu Lee, M.D.
-
Sub-Investigator:
- Po-Jui Chang, M.D.
-
Sub-Investigator:
- Meng-Heng Hsieh, M.D.
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
20 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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.
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 4-month regimen (2HZPM/2HPM)
|
8 weeks of isoniazid, pyrazinamide, rifapentine, and moxifloxacin, followed by 9 weeks of isoniazid, rifapentine and moxifloxacin
Other Names:
|
NO_INTERVENTION: Standard 6-month regimen (2HERZ/4HR) historical control
a standard, six-month regimen, with
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment Efficacy
Time Frame: 12 months after study treatment assignment
|
TB disease-free survival at 12 months after study treatment assignment
|
12 months after study treatment assignment
|
Safety and tolerability
Time Frame: 0-4 months
|
The proportion of participants with grade 3 or higher adverse events during study drug treatment
|
0-4 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Early sterilizing activity
Time Frame: 8 weeks
|
The proportion of patients with a negative sputum culture at the end of intensive phase therapy at 8 weeks
|
8 weeks
|
Sputum culture conversion
Time Frame: 4, 8, 12, 17 weeks, 6 months, 12 months
|
Time to stable sputum culture conversion
|
4, 8, 12, 17 weeks, 6 months, 12 months
|
Speed of decline of sputum viable bacilli
Time Frame: 2-8 weeks
|
Speed of decline of sputum viable bacilli by automated mycobacteria growth indicator tube (MGIT) days to detection
|
2-8 weeks
|
TB disease-free survival at 12 months sensitivity analysis (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 unfavorable outcome (Sensitivity analyses assuming all losses to follow-up and non-TB deaths have an unfavorable outcome)
|
12 months
|
TB disease-free survival at 12 months sensitivity analysis (favorable 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)
|
12 months
|
Rate of treatment discontinuation
Time Frame: 0-4 months
|
Rates of treatment discontinuation for reasons other than ineligibility (late exclusions due to drug resistance or HIV status)
|
0-4 months
|
All-cause mortality
Time Frame: 4, 12 months
|
All-cause mortality at 4 months and 12 months post-treatment assignment
|
4, 12 months
|
Attributable mortality
Time Frame: 4, 12 months
|
Attributable mortality at 4 months and 12 months post-treatment assignment
|
4, 12 months
|
Changes in interferon-gamma levels
Time Frame: 2, 4, 8, 12 weeks
|
Changes in interferon-gamma levels during treatment compared to baseline
|
2, 4, 8, 12 weeks
|
Changes in tumor necrosis factor-alpha levels
Time Frame: 2, 4, 8, 12 weeks
|
Changes in tumor necrosis factor-alpha levels during treatment compared to baseline
|
2, 4, 8, 12 weeks
|
Changes in interleukin-12 and interleukin-6 levels
Time Frame: 2, 4, 8, 12 weeks
|
Changes in interleukin-12 and interleukin-6 levels during treatment compared to baseline
|
2, 4, 8, 12 weeks
|
Changes in triggering receptor expressed on myeloid cells-1 (TREM-1) levels
Time Frame: 2, 4, 8, 12 weeks
|
Changes in triggering receptor expressed on myeloid cells-1 (TREM-1) levels during treatment compared to baseline
|
2, 4, 8, 12 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HLA associations with severe drug adverse events
Time Frame: 0-4 months
|
HLA Genotyping to detect predictors for occurrence of severe drug adverse events including skin rash and hepatitis.
|
0-4 months
|
Maximum plasma concentration (Cmax) of rifapentine
Time Frame: 0, 2, 4, 8, 12 weeks
|
Serum concentration of rifapentine by determining area under the curve
|
0, 2, 4, 8, 12 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ANTICIPATED)
May 1, 2021
Primary Completion (ANTICIPATED)
December 31, 2023
Study Completion (ANTICIPATED)
December 31, 2024
Study Registration Dates
First Submitted
March 31, 2021
First Submitted That Met QC Criteria
April 22, 2021
First Posted (ACTUAL)
April 23, 2021
Study Record Updates
Last Update Posted (ACTUAL)
April 23, 2021
Last Update Submitted That Met QC Criteria
April 22, 2021
Last Verified
April 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Lung Diseases
- Bacterial Infections
- Bacterial Infections and Mycoses
- Gram-Positive Bacterial Infections
- Actinomycetales Infections
- Mycobacterium Infections
- Tuberculosis
- Tuberculosis, Pulmonary
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Anti-Bacterial Agents
- Leprostatic Agents
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 CYP3A Inducers
- Antitubercular Agents
- Antibiotics, Antitubercular
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2C8 Inducers
- Cytochrome P-450 CYP2C19 Inducers
- Cytochrome P-450 CYP2C9 Inducers
- Moxifloxacin
- Rifapentine
- Rifampin
Other Study ID Numbers
- KSVGH-20561
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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