Clinical trial NCT06727864: Short Course Regimen in Low Risk Active Tuberculosis- a Multicenter, Randomized, Active-controlled, Trial
Official title: Safety and Efficacy of Four-month Short Course Regimen in Low Risk Active Tuberculosis- a Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Pulmonary Tuberculosis
Keywords: tuberculosis
short course regimen
safety
sputum conversion
recurrence rate
Lead sponsor: Kaohsiung Veterans General Hospital.
Sponsor class: OTHER
Collaborators: name: Taipei Veterans General Hospital, Taiwan
name: National Taiwan University Hospital
name: Chang Gung Memorial Hospital
name: Far Eastern Memorial Hospital
name: E-DA Hospital
name: Kaohsiung Medical University
First posted: 2024-12-11
Enrollment: 270
Sex: ALL
Minimum age (years): 20
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two months of isoniazid (H), pyrazinamide (Z), rifampicin (R), and pyrazinamide (Z) Subsequent orders are for H(E)Z for another two months
Primary purpose: TREATMENT

Brief summary: Tuberculosis remains an important global health problem, and the world is currently not on track to end the TB epidemic by 2030. With the concerted efforts of the government and medical community, the incidence of TB in Taiwan has gradually decreased, however, Taiwan remains an endemic area for TB. The development of efficacious, safe, and shorter treatment regimens could significantly improve treatment completion rate and reduce transmission of TB. The current treatment guidelines for drug-susceptible TB from the World Health Organization (WHO), American Thoracic Society (ATS), United States Center for Diseases Control (U.S. CDC), Infectious Diseases Society of America (IDSA) and European Respiratory Society (ERS) include 2 months of isoniazid, rifampin, pyrazinamide and ethambutol (HREZ), followed by 4 months of isoniazid, rifampin, and ethambutol(HRE). The current treatment regimen requires 6 months of treatment, despite being highly efficacious, requires long duration of treatment. Adherence to treatment is the major barrier which poses a negative impact to TB control, and increased cost to both the patient and the public health system. Developing an efficacious, safe and short treatment regimen can significantly improve TB management and treatment success rates.

Detailed description: This prospective, multicenter, randomized, open-labeled 3-year study, will recruit 270 adult patients with newly diagnosed tuberculosis with low risk of recurrence, and randomized 1:1 to a 4 months 2HREZ/2HRE (n=135) versus standard, 6 months regimen 2HREZ/4HRE (n=135). Expected enrollment will be 90 patients in year 1, 90 in year 2 and 90 in year 3.

This study aims to evaluate the efficacy, safety and long-term recurrence rate of a short-course, 4-months regimen including 2HREZ/2HRE compared with the standard 6-months regimen, 2HREZ/4HRE, and the impact of short regimen on reducing the costs and loading to the public health and medical system

Eligibility criteria: Inclusion Criteria:

* Newly diagnosed pulmonary tuberculosis patients combined with any of the following diagnostic conditions:

  * at least one set of sputum specimens is positive for Mycobacterium tuberculosis culture or TB PCR test; or
  * pathological and histological findings of typical tuberculosis manifestations;
  * clinical diagnosis and Physician determines the need for complete anti-tuberculosis treatment
* Those who have had tuberculosis in the past and have been cured for at least three years can be included
* Aged over 20 years old
* Laboratory data at the time of inclusion in the study or within 14 days:

  * Serum or plasma glutamic acid pyruvate transaminase (ALT) value ≦ three times the upper limit of normal
  * Serum or plasma total bilirubin ≦ 2.5 times the upper limit of normal
  * Serum or plasma creatinine ≦ twice the upper limit of normal or creatinine clearance greater than 30 mL/min
  * Heme ≧7.0 g/Dl
  * Platelets ≧100,000/mm3
* Patient signs consent form
* Patients who agree to join and cooperate with the county and city health bureau's urban treatment plan to ensure medication compliance.

Exclusion Criteria:

* The acid-fast smear of sputum or respiratory specimen is strongly positive (≥ 2+)
* Chest X-ray or lung computed tomography combined with open lesions
* Chest X-ray or lung computed tomography shows extensive lesions and the clinician judges that short-term treatment is not suitable
* Simultaneous combination of intrapulmonary and extrapulmonary tuberculosis
* People who are unable to take oral medications
* People who have participated in this research
* Have used anti-tuberculosis drugs for more than 14 days
* A history of tuberculosis suspected or diagnosed as central nervous system tuberculosis, bone or joint tuberculosis, miliary tuberculosis or tuberculous pericarditis.
* Known history of allergy or intolerance to this study drug
* Patients with HIV infection, organ transplantation, and chronic renal failure
* Long-term use of immunosuppressive drugs, including steroid use \>10mg/day (more than 30 consecutive days in the last three months)
* Late exclusion: Mycobacterium tuberculosis is known to be resistant to any one or more of the following drugs: rifampin, isoniazid, ethambutol

Primary outcomes:
measure: TB disease free survival at 12 months post-randomization
timeFrame: 12 months
measure: TB disease free survival at 24 months post randomization
timeFrame: 24 months
measure: Grade 3-5 adverse events
timeFrame: From enrollment to the end of treatment at 4 or 6 months
Secondary outcomes:
measure: Early sterilizing activity
timeFrame: 8 weeks
measure: Sputum culture conversion
timeFrame: 4, 8, 12, 16,20,24 weeks,3, 6, 12 and 24 months after treatment
measure: All-cause mortality
timeFrame: 4, 12 months
measure: Attributable mortality
timeFrame: 4, 12 months
measure: Changes in interferon-gamma levels
timeFrame: 2, 4, 8, 12,16or 24 weeks
measure: Changes in tumor necrosis factor-alpha levels
timeFrame: 2, 4, 8, 12,16or 24 weeks
measure: Changes in interleukin-12 and interleukin-6 levels
timeFrame: 2, 4, 8, 12,16or 24 weeks
measure: Changes in triggering receptor expressed on myeloid cells-1 (TREM-1) levels
timeFrame: 2, 4, 8, 12,16or 24 weeks
Other outcomes:
measure: HLA associations with severe drug adverse events
timeFrame: Upon joining or within two weeks of study entry
Locations:
city: New Taipei
country: Taiwan
facility: Far Eastern Memorial Hospital
state: Bangiao
city: Taichung
country: Taiwan
facility: Taichung Hospital
state: West
city: Kaoshiung
country: Taiwan
facility: E-DA Healthcare Group
state: Yanchao
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
Study officials:
affiliation: Kaohsiung Veterans General Hospital.
name: Susan Shin-Jung Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: