Short Course Regimen in Low Risk Active Tuberculosis- a Multicenter, Randomized, Active-controlled, Trial

NCT06727864 | Recruiting Phase 3

• 1 other identifier: KSVGH24-CT2-16
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 8

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.

Conditions

Pulmonary Tuberculosis

Keywords

tuberculosis; short course regimen; safety; sputum conversion; recurrence rate

Outcome Measures

Primary Outcomes (3)

• TB disease free survival at 12 months post-randomization

  Number of participants without TB disease at 12 months after randomization

  12 months

• TB disease free survival at 24 months post randomization

  Number of participants without TB disease at 24 months after randomization

  24 months

• Grade 3-5 adverse events

  Development of Grade3-5 adverse events during treatment

  From enrollment to the end of treatment at 4 or 6 months

Secondary Outcomes (8)

• Early sterilizing activity

  8 weeks

• Sputum culture conversion

  4, 8, 12, 16,20,24 weeks,3, 6, 12 and 24 months after treatment

• All-cause mortality

  4, 12 months

• Attributable mortality

  4, 12 months

• Changes in interferon-gamma levels

  2, 4, 8, 12,16or 24 weeks

Other Outcomes (1)

• HLA associations with severe drug adverse events

  Upon joining or within two weeks of study entry

Study Arms (2)

Intervention/Treatment

EXPERIMENTAL

Two months of isoniazid (H), ethambutol (E), rifampicin (R) and Pyrazinamide (Z) followed by HR(E) for another two months

Drug: 4-month regimen (2HERZ/2HRE)

6-months HERZ (2HERZ/4HRE)

ACTIVE COMPARATOR

Two months of isoniazid (H), pyrazinamide (Z), rifampicin (R) and Pyrazinamide (Z) followed by HR(E) for another four months

Drug: 6-month (2HERZ/4HRE)

Interventions

4-month regimen (2HERZ/2HRE) DRUG

4-month (2HERZ/2HRE)

Intervention/Treatment

6-month (2HERZ/4HRE) DRUG

2 months of HREZ followed by 4 months of HR/HRE

6-months HERZ (2HERZ/4HRE)

Eligibility Criteria

• Age: 20 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Kaohsiung Veterans General Hospital.: lead
• Taipei Veterans General Hospital, Taiwan: collaborator
• National Taiwan University Hospital: collaborator
• Chang Gung Memorial Hospital: collaborator
• Far Eastern Memorial Hospital: collaborator
• E-DA Hospital: collaborator
• Kaohsiung Medical University: collaborator

Study Sites (8)

Far Eastern Memorial Hospital

New Taipei City, Bangiao, 220, Taiwan

RECRUITING

Taichung Hospital

Taichung, West, 199, Taiwan

RECRUITING

E-DA Healthcare Group

Kaoshiung, Yanchao, 82445, Taiwan

RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

RECRUITING

Kaohsiung Veterans General Hospital

Kaohsiung City, 813, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 112, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, Taiwan

RECRUITING

Linkou Chang Gung Memorial Hospital

Taoyuan, 333, Taiwan

RECRUITING

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Interventions

Clinical Protocols

Condition Hierarchy (Ancestors)

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)

Therapeutics; Epidemiologic Study Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation

Study Officials

• Susan Shin-Jung Lee, MD, PhD

  Kaohsiung Veterans General Hospital.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Susan Shin-Jung Lee, M.D., Ph.D.

CONTACT

+886-7342-2121; ssjlee28@yahoo.com.tw

Mei-Ling Lin, University

CONTACT

+886-7342-2121; ed101622@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: 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 physician

Model Details: Two months of isoniazid (H), pyrazinamide (Z), rifampicin (R), and pyrazinamide (Z) Subsequent orders are for H(E)Z for another two months

Study Record Dates

• First Submitted: December 6, 2024
• First Posted: December 11, 2024
• Study Start: January 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 25, 2025

Record last verified: 2024-12

Locations

TW (8)