Clinical trial NCT06905522: A PAN-USR TB Multi-Center Trial
Official title: A Pan-Ultrashort Regimen for Drug-susceptible and Drug-resistant Pulmonary Tuberculosis: a Multi-Center Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Pulmonary Tuberculosis
Lead sponsor: Shenzhen Third People's Hospital
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital of Zhejiang University
name: Beijing Chest Hospital of Capital Medical University
name: Shenyang Tenth People's Hospital
name: The Sixth People's Hospital of the Xinjiang Uygur Autonomous Region
name: The Fourth Hospital of Inner Mongolia Autonomous Region
name: Guizhou Aerospace Hospital
First posted: 2025-04-01
Enrollment: 610
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Tuberculosis (TB) remains a major public health issue and one of the top ten causes of death from a single infectious disease worldwide. China is among the countries with the highest TB burden, ranking third globally for total TB cases and second for drug-resistant TB cases. PAN-TB is an innovative concept in TB treatment, aiming to develop a universal regimen effective for all forms of active TB, including both drug-susceptible and drug-resistant strains. The primary goal of the PAN-TB regimen is to simplify the treatment process, reduce costs, and improve treatment success rates. The ideal Target Regimen Profile (TRP) for PAN-TB includes superior efficacy compared to standard treatment for non-drug-resistant TB, a reduced treatment duration from the current 4-6 months to 2-3 months, and improved safety and tolerability. This project aims to explore a new ultra-short-course treatment regimen for both drug-sensitive (DS-TB) and drug-resistant TB (MDR/RR-TB), which aligns with the latest trends in TB treatment both domestically and internationally. The regimen also has significant practical implications for enhancing treatment efficacy and reducing patient burden. Furthermore, the study will explore the identification of new biomarkers closely linked to treatment outcomes over the course of full-cycle therapy.


Eligibility criteria: Inclusion criteria:

1. Age range from 18 to 65 years old, regardless of gender;
2. Clinical symptoms and/or pulmonary imaging (chest X-ray or chest CT) support the diagnosis of active pulmonary tuberculosis;
3. Microbiological testing (molecular or phenotypic) confirms the presence of Mycobacterium tuberculosis, whether resistant to rifampicin or not; Recommend using respiratory specimens for GeneXpert MTB/RIF testing;
4. Voluntarily sign the informed consent form for participating in this project and be able and willing to accept follow-up visits;
5. Willing to undergo HIV testing;
6. Willing to preserve samples including DNA;
7. For women with fertility, they have a negative serum or urine pregnancy test within 3 days before enroll the study and be willing to use effective contraceptive measures during the study period. Female subjects without fertility must have records of menopause, hysterectomy, bilateral oophorectomy, or bilateral tubal ligation. Acceptable forms of contraception include condoms, intrauterine devices, cervical caps with spermicides, and diaphragm with spermicides.

Exclusion criteria:

1. Prior to this study, patients who were diagnosed with active pulmonary tuberculosis and had received anti-tuberculosis treatment (including first-line and second-line anti-tuberculosis drugs);
2. Intolerance or allergy to any investigational drug (i.e., bedaquiline, linezolid, fluoroquinolones \[including moxifloxacin, sitagliptin\], pyrazinamide);
3. Resistance to any investigational drug (i.e., bedaquiline, linezolid, fluoroquinolones \[including moxifloxacin, sitagliptin\], pyrazinamide). The following detection methods can be used: tNGS or other drug sensitivity testing methods (such as GeneXpert MTB/XDR, dissolution curve method, phenotypic drug sensitivity, etc.);
4. Suffering from hematogenous disseminated tuberculosis or coexisting with extrapulmonary tuberculosis (as specified in this study, the scope of pulmonary tuberculosis includes: simple pulmonary tuberculosis, pulmonary tuberculosis + tuberculous pleurisy/bronchial tuberculosis/mediastinal lymph node tuberculosis. Extrapulmonary tuberculosis refers to tuberculosis other than the chest-related types mentioned above);
5. Presence of non-tuberculous mycobacteria or other microbial lung infections that affect treatment outcomes;
6. Simultaneously using drugs that affect the efficacy of this study or have contraindications for combination therapy;
7. Use of any immunosuppressive medication or systemic glucocorticoids for more than 2 weeks before screening;
8. Any medication currently used or planned to be used that is known to significantly prolong the QTc interval, including but not limited to: amiodarone, amitriptyline, chloroquine, chlorpromazine, cisapride, dipyridamole, itraconazole, procaine, quinidine, or sotalol;
9. Uncontrolled blood sugar in diabetes, with no likelihood of improving blood sugar status according to the judgment of the researchers;
10. HIV positive;
11. Coexisting with severe autoimmune diseases, severe liver and kidney dysfunction, psychiatric disorders, hematological disorders, or malignant tumors;
12. Laboratory parameters within 14 days prior to recruitment: (1) Serum AST and ALT levels ≥ 3 times the upper limit of normal (ULN); (2) Blood creatinine ≥ 2 times ULN; (3) Hemoglobin ≤ 70 g/L; (4) Platelet count ≤ 50 × 10\^9/L; (5) Blood potassium levels are ≥ 5.5 mmol/L or ≤ 3.5 mmol/L;
13. ECG QTcF ≥450 ms (allowing for one re-test during the screening phase to reassess eligibility for inclusion); Presence of one or more risk factors that could cause QT interval prolongation, such as arrhythmia, myocardial ischemia, etc.; history or family history of long QT syndrome;
14. Women who are pregnant or breastfeeding;
15. Weight \<30 kg, or ≥90 kg;
16. The patient has participated in clinical trials of other drugs within the past 3 months during the screening period;
17. Other conditions deemed unsuitable for participation in the study by the research doctors.

Primary outcomes:
measure: Unfavorable outcomes
timeFrame: 12 months (52 weeks)
measure: Safety
timeFrame: 2 months (9 weeks)
Secondary outcomes:
measure: Sputum culture conversion rate
timeFrame: 2 months (9 weeks) after randomization
measure: Unfavorable outcomes (short-term)
timeFrame: 6 months (26 weeks) after randomization
measure: Unfavorable outcomes (mid-term)
timeFrame: 18 months (78 weeks) after randomization
measure: Time to sputum culture conversion
timeFrame: Median time
measure: Serious adverse events or grade 3 or higher adverse events (short-term)
timeFrame: 12 months (52 weeks) after randomization
measure: Serious adverse events or grade 3 or higher adverse events (mid-term)
timeFrame: 18 months (78 weeks) after randomization
measure: Adverse events during treatment
timeFrame: 9 or 13 weeks (A1, A2); 26 weeks (B, C)
measure: QTcF prolongation during treatment
timeFrame: 9 or 13 weeks (A1, A2); 26 weeks (B, C)
measure: Liver function damage during treatment
timeFrame: 9 or 13 weeks (A1, A2); 26 weeks (B, C)
Other outcomes:
Locations:
Study officials:
References:
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