Evaluation of the Efficacy and Safety of a 4-month Daily Regimen (2HZPM/2HPM) for Treatment of Pulmonary TB (ESCAPE-TB)

July 11, 2024 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

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
333

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Hsin-Wei Tung, R.N.
  • Phone Number: 2062 +886-7342-2121

Study Locations

  • Taiwan
      • Kaohsiung, Taiwan, 813
        • Kaohsiung Veterans General Hospital
      • Taipei, Taiwan
        • National Taiwan University Hospital
      • Taipei, Taiwan, 112
        • Taipei Veterans General Hospital
      • Taoyuan City, Taiwan, 333
        • Linkou Chang Gung Memorial Hospital

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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
  2. Patient with a history of being untreated for 3 years after cure from a previous episode of TB can be included.
  3. Age 20 years or older
  4. 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.

  5. 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
  6. Patient signed a written informed consent

Exclusion Criteria:

  1. Pregnant or breast-feeding.
  2. Unable to take oral medications.
  3. Previously enrolled in this study.
  4. Received any investigational drug in the past 3 months.
  5. More than 14 days of systemic treatment with any antituberculous drugs preceding initiation of study drugs.
  6. Known history of prolonged QT syndrome.
  7. Suspected or documented TB involving the central nervous system and/or bones and/or joints, and/or miliary tuberculosis and/or pericardial tuberculosis.
  8. Weight less than 40.0 kg.
  9. Known allergy or intolerance to any of the study medications.
  10. 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.
  11. Medical conditions, including HIV infection and others conditions that, in the investigator's judgment, make study participation not in the individual's best interest.
  12. 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 Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 4-month regimen (2HZPM/2HPM)
  • 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
Drug: 4-month rifapentine-based regimen
8 weeks of isoniazid, pyrazinamide, rifapentine, and moxifloxacin, followed by 9 weeks of isoniazid, rifapentine and moxifloxacin
Other Names:
  • moxifloxacin
  • priftin
  • rifapentine
No Intervention: Standard 6-month regimen (2HERZ/4HR) historical control

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 the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
12 months after study treatment assignment
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
0-4 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Early sterilizing activity (Negative sputum cultures at end of intensive 8 weeks phase)
Time Frame: 8 weeks
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
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
Number of days from start of treatment to first negative sputum culture that remain negative thereafter
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
Number of days from loading of sputum culture into MGIT to the day of detection of viable mycobacteria
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
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
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
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
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
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
0-4 months
All-cause mortality at 4 months post-treatment assignment
Time Frame: 4 months
Number of participants who died at 4 months divided by number of participants
4 months
All-cause mortality at 12 months post-treatment assignment
Time Frame: 12 months
Number of participants who died at 12 months divided by number of participants
12 months
Attributable mortality at 4 months post-treatment assignment
Time Frame: 4 months
Number of patients who died due to reasons attributable to tuberculosis at 4 months post-treatment assignment divided by number of participants
4 months
Attributable mortality at 12 months post-treatment assignment
Time Frame: 12 months
Number of patients who died due to reasons attributable to tuberculosis at 12 months post-treatment assignment divided by number of participants
12 months
Changes in interferon-gamma levels during treatment compared to baseline
Time Frame: 2, 4, 8, 12 weeks
interferon-gamma levels during treatment minus baseline levels
2, 4, 8, 12 weeks
Changes in tumor necrosis factor-alpha levels during treatment compared to baseline
Time Frame: 2, 4, 8, 12 weeks
Tumor necrosis factor-alpha levels during treatment minus baseline levels
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
Interleukin-12 levels during treatment minus baseline levels
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
Triggering receptor expressed on myeloid cells-1 (TREM-1) levels during treatment minus baseline levels
2, 4, 8, 12 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
HLA Genotyping to detect predictors for occurrence of severe drug adverse events including skin rash and hepatitis.
Time Frame: 0-4 months
Identify HLA genotypes associated with severe drug adverse events such as greater than grade 2 hepatitis and/or skin rash
0-4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Kaohsiung Veterans General Hospital.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Chang Gung Memorial Hospital
Taipei Veterans General Hospital, Taiwan
National Taiwan University
Centers for Disease Control, Taiwan

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Susan Shin-Jung Lee, M.D., Ph.D., Kaohsiung Veterans General Hospital.

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2023

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 31, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 22, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 23, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 12, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 11, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KSVGH21-CT5-49

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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