PAN-USR: a universal ultra-short treatment for pulmonary tuberculosis

A Pan-Ultrashort Regimen for Drug-susceptible and Drug-resistant Pulmonary Tuberculosis: A Multi-Center Randomized Controlled Trial

This trial tests whether a new 2–3 month drug regimen works and is safe for adults with active pulmonary tuberculosis, including drug-resistant cases.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 610 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Shenzhen Third People's Hospital (other)
• Locations: 3 sites (Beijing and 2 other locations)
• Trial ID: NCT06905522 on ClinicalTrials.gov

What this trial studies

PAN-USR is a Phase 3, multi-center interventional trial in China testing an ultra-short PAN-TB regimen intended to treat both drug-susceptible and drug-resistant pulmonary tuberculosis. The regimen combines bedaquiline, sitafloxacin, linezolid, pyrazinamide, and isoniazid and aims to shorten treatment to about 2–3 months while maintaining or improving cure rates and safety. Adults 18–65 with microbiologically confirmed pulmonary TB (rifampicin-resistant or not) who consent to follow-up, HIV testing, and sample storage are eligible and will be treated and monitored at participating hospitals. Outcomes will include treatment success, time to sputum conversion, and safety/tolerability measures.

Who should consider this trial

Good fit: Adults aged 18–65 with clinical and microbiological confirmation of active pulmonary tuberculosis, including rifampicin-resistant cases, who can consent, attend follow-up visits, agree to HIV testing, and comply with sample and contraception requirements are ideal candidates.

Not a fit: People under 18 or over 65, those without microbiological confirmation of pulmonary TB, pregnant women, or anyone unwilling to undergo required testing, sample storage, contraception, or follow-up visits are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this regimen could shorten TB treatment to 2–3 months, simplify care, reduce costs, and improve cure rates for both drug-susceptible and drug-resistant TB.

How similar studies have performed: Combinations including bedaquiline and linezolid have shown promise for drug-resistant TB, but a universal 2–3 month regimen for both drug-susceptible and drug-resistant TB remains experimental and not yet proven at scale.

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.

Where this trial is running

Beijing and 2 other locations

• Beijing Chest Hospital of Capital Medical University — Beijing, China (RECRUITING)
• Shenzhen Third People's Hospital — Shenzhen, China (RECRUITING)
• The Sixth People's Hospital of the Xinjiang Uygur Autonomous Region — Ürümqi, China (RECRUITING)

Study contacts

• Study coordinator: Professor Lu

Conditions: Pulmonary Tuberculosis