Pulmonary Tuberculosis, Rifampicin-resistant Tuberculosis
Conditions
Keywords
tuberculosis, Rifampicin-resistant, short regimen, contezolid, delamanid
Brief summary
The goal of this clinical trial is to compare the efficacy and safety of a Contezolid and Delamanid-Containing short regimen to standard longer regimen in Rifampicin-resistant pulmonary tuberculosis (RR-TB). The main questions it aims to answer are: * Is the efficacy of short regimen non-inferior to standard regimen? * Is the short regimen safe enough to replace the standard regimen? Participants will: * Be given with either short or standard regimen for RR-TB treatment * Be asked to complete the scheduled visit as planned.
Interventions
DRUGBedaquiline
Oral, 400mg qd for 2 weeks, then 200 mg 3 times per week
DRUGDelamanid
Oral, 100mg bid
DRUGContezolid
Oral, 800mg bid
DRUGLevofloxacin
Oral, 400mg qd for weight \<50kg, 600-750mg qd for weight ≥50kg
DRUGMoxifloxacin
Oral, 400mg qd
DRUGClofazimine
Oral, 100mg qd
DRUGLinezolid
Oral, 600mg qd
DRUGCycloserine
Oral, 250mg bid
DRUGProthionamide
Oral, 600mg qd for weight \<50kg, 600-800mg qd for weight ≥50kg
DRUGPyrazinamide
Oral, 1500mg qd for weight \<50kg, 1750mg qd for weight ≥50kg
DRUGPara-Aminosalicylic Acid
8000mg qd for weight \<50kg, 10000mg qd for weight ≥50kg
DRUGEthambutol
750mg qd for weight \<50kg, 1000mg qd for weight ≥50kg
Sponsors
National Medical Center for Infectious Diseases
Beijing Chest Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18y and \<70y when signing informed consent; 2. Initial or re-treatment for pulmonary tuberculosis with: 1\) MTB positive in sputum or bronchoalveolar lavage fluid culture at or within 3 months before screening, or MTB positive in molecular test at or within 3 months before screening, and; 2) recorded Rifampicin-resistance at or before screening; 3. Imaging (Chest X-ray or CT scan) proved pulmonary tuberculosis within 1 year before screening; 4. Never used BDQ, DLM or CZD, or the accumulative duration of any of the treatment is not more than 2 weeks 5. For women in childbearing age, negative in pregnancy test and effective contraceptive measures throughout study is required; 6. For men, effective contraceptive measures is required; 7. Willing to participate the study and sign informed consent.
Exclusion criteria
1. The participant will be excluded by investigator based on the medical history or concomitant diseases such as serious metabolic disease, cardiovascular disease, hepatobiliary disease, renal disease, autoimmune disease, neuropsychiatric disorders, hematological disease, malignant neoplastic disease and so on; or the study will have negative impact on the well-being of the participant, or the participant is considered unable to complete the evaluation by investigator; 2. History of alcohol or drug abuse that the study is considered have negative impact on the well-being of the participant by investigator; 3. HIV positive; 4. Chronic hepatitis with HBsAg, HBeAg and anti-HBC antibody positive, or HBV-DNA\>1000 CPs/mL with rising ALT/AST; 5. Allergic to or known hypersensitive to any of study drugs; 6. Extensive (or advanced) pulmonary TB disease: presence of bilateral cavitary disease or extensive parenchymal damage on chest radiography; 7. Hematogenous disseminated pulmonary tuberculosis and serious extrapulmonary tuberculosis (such as tuberculosis in digestive system, urogenital system, osteoarticular tuberculosis, tuberculous meningitis); 8. With any of following risk factors for cardiovascular disease: 1) history of arrhythmia and on consequential treatment; 2) QTcF\>500ms on ECG; 3) history of ventricular arrhythmia; 4) torsade de pointe with heart failure, hypokalemia or familial long Q-T syndrome; 5) other possible risk factor for arrythmia; 9. Previous or current optic nerve disorder that may progress or deteriorate during the study by investigator's consideration; 10. Was enrolled within 2 months before screening, or currently in other studies; except for those who participating observational study or in the post-treatment period; 11. Being considered unlikely to survive for more than 6 months by investigator; 12. BMI \< 17kg/m2 13. May need surgical procedures based on the evaluation of pulmonary lesions; 14. May continuous use prohibited concomitant medications that is considered not suitable for the study by investigator; 15. Positive in pregnancy test or known pregnancy, breastfeeding, or plan to become pregnant during or within 6 months after the study treatment; 16. Abnormal laboratory test results: 1) Plasma potassium lower than lower limit of normal (LLN); 2) Hb \< 8.0 g/dL； 3) platelet count \<75,000/mm3； 4) WBC count\<3000/mm3； 5）AST/ALT \>3×ULN； 6）creatinine\>2×ULN；7）total bilirubin\>2×ULN, or \>1.5×ULN，with abnormal AST or ALT; 8) Albumin \< 30g/L
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Favourable outcome rate at 24 months after randomization | from randomization to 24 months after | The proportion of participants with a favourable outcome. A participant's outcome will be classified as favourable if their last two sputum culture results are negative unless they have previously been classified as unfavourable. These two cultures must be taken on separate visits (with ≥28d interval); the latest of which not being earlier than month 23 from randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Unfavourable outcome rate at 24 months after randomization | from randomization to 24 months after | Including 1. Death; 2. Treatment failure 3. Lost-to-follow-up 4. Treatment Discontinuation 5. Ttreatment prolonging 6. Still on treatment at the end of follow up 7. Recurrence |
| Time to culture conversion | from randomization to 24 months after | Time from treatment initiation to first negative result in sputum culture confirmed by two consecutive cultures with an interval of ≥28d |
| Grade 3 or higher adverse event rate | from randomization to 24 months after | Proportion of participants experiencing at least one grade 3 or higher adverse event, or serious adverse event defined by the Division of AIDS severity criteria for adverse events |
Other
| Measure | Time frame | Description |
|---|---|---|
| Contezolid plasma concentration | 7d±3d after the first dose of contezolid | To build the population PK model of contezolid with steady-state plasma concentration, measured by blood samples taken at four time points around one administration: ≤15min before and 1h±15min, 2h±15min, 3h±15min after. The index adiministration should be in 7d±3d after the first dose of contezolid. |
Countries
China
Outcome results
None listed