tuberculosis,diabetes mellitus
Conditions
Interventions
Expriment group A1:Participants classified as low treatment difficulty are randomized at baseline in a 1:1:1 ratio to Arm A1. They receive daily isoniazid, rifapentine 1200 mg, moxifloxacin, and pyraz
Expriment group A2:Participants classified as low treatment difficulty are randomized at baseline in a 1:1:1 ratio to Arm A2. They receive daily isoniazid, rifapentine 900 mg, moxifloxacin, and pyrazi
Control group A3:Participants classified as low treatment difficulty are randomized at baseline in a 1:1:1 ratio to the control arm A3. They receive daily isoniazid, rifampicin, pyrazinamide, and etha
Expriment group B1:Participants classified as high treatment difficulty first receive a uniform regimen for 6 months. At month 6, those who meet the microbiological Hard Gate are randomized 1:1 to the
Control group B2:Participants classified as high treatment difficulty also first receive the same uniform 6-month regimen. At month 6, those who meet the microbiological Hard Gate are randomized 1:1 t
Sponsors
Shenzhen Third People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Informed Consent: The subject (or their legally authorized representative) has voluntarily signed and dated the written Informed Consent Form (ICF) prior to any study-related procedures, and is able to comply with the study visit schedule and examination requirements; 2 Age: Aged 18 to 70 years old (inclusive) at the time of signing the ICF, with no gender restriction; 3. Confirmed Type 2 Diabetes Mellitus (T2DM): Diagnosis of T2DM in accordance with the WHO (1999) or ADA diagnostic criteria (either previously diagnosed or newly diagnosed during screening). 4. Confirmed Active Pulmonary Tuberculosis: Must meet all of the following:(1) Positive molecular test for Mycobacterium tuberculosis (one of Xpert MTB/RIF, Xpert Ultra, or tNGS);(2) Molecular test confirming rifampicin-susceptible TB (one of Xpert MTB/RIF, Xpert Ultra, or tNGS);(3) Radiological support (chest radiograph or CT showing pulmonary lesions consistent with active pulmonary tuberculosis);(4) Disease extent includes uncomplicated pulmonary tuberculosis, or pulmonary tuberculosis complicated by tuberculous pleurisy, endobronchial tuberculosis, or mediastinal lymph node tuberculosis; 5. Prior Treatment History No prior anti-tuberculosis treatment for the current episode, or receipt of anti-tuberculosis treatment (including fluoroquinolones or injectable anti-tuberculosis agents) for = 30 kg and < 90 kg at screening; 7. Contraception Requirements: Females of childbearing potential must have a negative serum or urine pregnancy test at screening; All subjects of childbearing potential (male and female) agree to use highly effective contraception (annual failure rate < 1%) from signing the ICF until at least 6 months after the last study drug administration. Male subjects must use condoms throughout the study; 8. Compliance and Access: The investigator judges that the subject has the ability to complete treatment and long-term follow-up, and has reliable contact information / is able to complete electronic follow-up or equivalent alternative follow-up.
Exclusion criteria
Exclusion criteria: 1. Drug Resistance Risk: Known or suspected resistance to any of the core study drugs (isoniazid, rifamycins, fluoroquinolones, pyrazinamide), or inability to rule out drug resistance prior to randomization; 2. Extrapulmonary Tuberculosis Requiring Prolonged or Specialized Treatment: Miliary tuberculosis, tuberculous meningitis/meningoencephalitis, spinal/osteoarticular tuberculosis, abdominal tuberculosis, genitourinary tuberculosis, pericardial tuberculosis, etc; 3. Nontuberculous Mycobacteria (NTM): High suspicion of NTM lung disease during screening (e.g., positive smear but "M. tb not detected" by molecular testing, or identification of NTM by tNGS/culture). 4. Acute Diabetic Complications: Presence of diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), or other acute metabolic disorders requiring urgent hospitalization during screening. 5. Severe Chronic Complications Interfering with Outcome Assessment: Including severe peripheral neuropathy (>= Grade 2, per DAIDS or study-predefined neurotoxicity grading criteria) or proliferative diabetic retinopathy/history of severe ocular hemorrhage; 6. Laboratory Safety Exclusions (within 14 days prior to screening): (1).Hepatic dysfunction: ALT or AST >= 3 × upper limit of normal (ULN), or total bilirubin (TBIL) >= 2 × ULN; (2).Renal insufficiency: Serum creatinine >= 2 × ULN or estimated glomerular filtration rate (eGFR) 5.5 mmol/L (hypokalemia may be rechecked after correction; subjects may be enrolled if results are acceptable). 7. Cardiac Safety Exclusions: (1).QTcF prolongation or significant cardiac history: Screening ECG QTcF > 450 ms in males or > 470 ms in females (one repeat ECG allowed if first result abnormal, using average value); (2).Or family history of long QT syndrome, clinically significant arrhythmia, myocardial infarction within the past 6 months, congestive heart failure, etc; 8. Drug–Drug Interactions: Requirement for long-term use of drugs with severe interactions with rifamycins for which no alternative agent is available; 9. Immunosuppression and Special Conditions: HIV positivity; systemic glucocorticoid therapy within 2 weeks prior to screening; current use of immunosuppressive agents/biologics; or severe autoimmune disease; 10. Other Conditions Affecting Safety or Compliance: History of fluoroquinolone-associated tendinitis/tendon rupture; hypersensitivity to any study drug component; severe psychiatric disorder; or severe chronic lung disease (in the investigator’s judgment, likely to interfere with outcome assessment); 11. Pregnancy or Lactation: Female subjects who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Relapse-free cure at PT-M12;Proportion of subjects with safety outcomes (SAE, Grade >=3 AE, AESI, etc.); | — |
Secondary
| Measure | Time frame |
|---|---|
| Favorable outcome rate at 24 months after treatment discontinuation;Time to recurrence;Proportion and time to culture conversion at key time points during treatment (e.g. W8, M2, M6, etc.);Proportion and time to treatment failure;Tuberculosis-related deaths and all-cause deaths.;Imaging improvement parameters (e.g., changes in chest radiograph score, proportion of cavity closure/reduction, etc.);Proportion of rescue therapy / protocol modification; | — |
Countries
China
Contacts
Public ContactDeng Guofang
Shenzhen Third People's Hospital
Outcome results
None listed