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

NCT04856644 | Active Not Recruiting Phase 3

• 1 other identifier: KSVGH21-CT5-49
• Study Type: interventional
• Target: 333
• Locations: 1 country
• Sites: 4

Brief 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 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.

Conditions

Tuberculosis, Pulmonary

Outcome Measures

Primary Outcomes (2)

• 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

  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

  0-4 months

Secondary Outcomes (14)

• Early sterilizing activity (Negative sputum cultures at end of intensive 8 weeks phase)

  8 weeks

• Time to stable sputum conversion (Time in days from conversion of a positive sputum culture to negative sputum culture)

  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

  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)

  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

Other Outcomes (2)

• 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

  0, 2, 4, 8, 12 weeks

Study Arms (2)

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

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

Interventions

4-month rifapentine-based regimen DRUG

8 weeks of isoniazid, pyrazinamide, rifapentine, and moxifloxacin, followed by 9 weeks of isoniazid, rifapentine and moxifloxacin

Also known as: rifapentine, moxifloxacin, priftin

4-month regimen (2HZPM/2HPM)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kaohsiung Veterans General Hospital.: lead
• National Taiwan University: collaborator
• Taipei Veterans General Hospital, Taiwan: collaborator
• Chang Gung Memorial Hospital: collaborator
• Centers for Disease Control, Taiwan: collaborator

Study Sites (4)

Kaohsiung Veterans General Hospital

Kaohsiung City, 813, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Linkou Chang Gung Memorial Hospital

Taoyuan, 333, Taiwan

Location

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

rifapentine; Moxifloxacin

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Susan Shin-Jung Lee, M.D., Ph.D.

  Kaohsiung Veterans General Hospital.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Masking will not be done
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending physiciian, Division of Infectious Diseases

Model Details: 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

Study Record Dates

• First Submitted: March 31, 2021
• First Posted: April 23, 2021
• Study Start: January 1, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: July 12, 2024

Record last verified: 2024-07

Locations

TW (4)