Multidrug-resistant tuberculosis
Conditions
Interventions
Group A:Bdq/Lzd/Mfx/Cs
Group B:Lzd/Mfx/Cs/Cfz/Z
Group C:Bdq/Lzd/Cs/Cfz/Z
Group D:Lzd/Cs/Cfz/Z+SASP
Sponsors
Shenzhen Third People's Hospital
Eligibility
Sex/Gender
All
Age
12 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Willing to participate in the study and sign informed consent or parental/guardian permission is provided (informed consent) for patients under 18 years old; 2. Aged 12 to 75 years, body weight >= 30kg, male or female; 3. Chest CT confirmed pulmonary tuberculosis, with or without Extensive TB disease (Definition of extensive pulmonary tuberculosis: Imaging findings of bilateral pulmonary cavities or diffuse pulmonary parenchymal lesions; Definition of extensive pulmonary tuberculosis in children under 15 years: imaging findings of pulmonary cavity or bilateral pulmonary lesions); 4. Diagnosis of rifampin-resistant tuberculosis by GeneXpert? MTB/RIF assay on sputum or bronchoalveolar lavage (BAL) specimen test within 3 months before screening; 5. Fluoroquinolones resistance results can be obtained during 1 month before treatment to 3 months after anti-tuberculosis treatment by rapid molecular biology methods(such as dissolution curve method, GeneXpert MTB/XDR or other rapid molecular biological methods), whole-genome sequencing methods, mass spectrometry, in vitro drug susceptibility tests, etc.; 6. Patients diagnosed as active pulmonary tuberculosis by clinical comprehensive assessment and requiring anti-tuberculosis treatment, including initial cases (no second-line anti-tuberculosis drugs have been used), treatment failure ((1)Second-line anti-tuberculosis drugs were used for more than 6 months and were judged as treatment failure; (2)Discontinuation of two or more anti-tuberculosis drugs can be judged as treatment failure) and re-positive TB test (recurrence or re-infection); 7. Women of childbearing age have a negative pregnancy urine test and agree to use high-efficiency contraception(such as condom or ligation, do not recommend drug contraception) during the study period. 8. Not leaving the local area during the study and willing to provide contact information to complete treatment and follow-up arrangements.
Exclusion criteria
Exclusion criteria: 1. Extrapulmonary tuberculosis: Other tuberculosis except for chest tuberculosis (such as simple pulmonary tuberculosis, pulmonary tuberculosis + tuberculous pleurisy / bronchial tuberculosis / mediastinal lymph tuberculosis); 2. Disseminated pulmonary tuberculosis or destroyed lung, whether Complicated with extrapulmonary tuberculosis; 3. Before starting treatment, existed resistance to bedaquinoline, linezolid, fluoroquinolones, cycloserine, clofazimine and pyrazinamide by rapid molecular biology methods, in vitro drug susceptibility tests, whole-genome sequencing methods or mass spectrometry; 4. Allergy or intolerant to treatment program; 5. Use of bedaquinoline or linezolid more than 1 month before entering the group( unless these drugs remain sensitive by DST evidence) 6. QTcF >= 450ms( Allow a retest to reassess eligibility during the screening phase), QTcF >= 450ms(Allow a retest to reassess eligibility during the screening phase ), one or more risk factors for QT prolongation, including pathological Q wave (defined as Q wave over 40 ms or depth over 0.4-0.5 mV) , Ventricular preexcitation, complete or clinically significant incomplete bundle branch block, secondary or tertiary cardiac block, Indoor conduction delay with QRS more than 120 ms and sinus bradycardia defined by sinus heart rate less than 50 bpm, Personal or family history of long QT syndrome, history of heart disease, syncope (such as cardiac syncope, excluding syncope caused by vasovagal nerve or epilepsy), symptomatic or asymptomatic arrhythmia (except sinus arrhythmia), and risk factors of tip torsion ventricular tachycardia ; 7. Hemoglobin less than 90g/L or platelets less than 75x10^9/L; 8. Impaired renal function (serum creatinine exceeds 1.5 times the upper limit of normal) 9. Impaired liver function (ALT and / or AST levels are three times the upper limit of normal), Liver cirrhosis (the Child-Pugh Grades B and C) or alcoholism; 10. Mental illness, such as epilepsy, severe depression, irritability or other psychosis; 11. Drug taking; 12. HIV positive or AIDS patients; 13.malignant tumour; 14.Patients with severe or other end-stage diseases, Severely ill patients who is impossible to survive more than six months or Karnofsky score < 50%; 15.In pregnant or breast-feeding women, unless the patient is willing to stop breast-feeding; 16. Using drugs that affect the observation of the curative effect or contraindicated with the drugs in this study, such as glucocorticoids, interferon, non-steroidal anti-inflammatory drugs, monoamine oxidase inhibitors (phenelzine, isocarb Hydrazine, etc.), direct or indirect sympathomimetic drugs (pseudoephedrine), vasopressor drugs (epinephrine, norepinephrine, etc.),dopamine drugs (dopamine, dobutamine, etc.), serotonin Reuptake inhibitors, tricyclic antidepressants, serotonin 5-HTI receptor antagonists (amitriptyline), serotonin 5-HTI receptor antagonists (amitriptyline, buspirone, etc.) and pethidine. 17. Those who participated in any other clinical trials; 18. According to the judgment of the researchers, the subject has any other disease that is not suitable for participating in this topic;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Unfavorable outcome; | — |
Secondary
| Measure | Time frame |
|---|---|
| culture conversion at 2 and 6 month;The incidence, frequency, duration, severity and prognosis of serious adverse events and pre-defined adverse events of special concern that can lead to changes in the treatment of tuberculosis (QT prolongation, peripheral neuropathy, optic neuritis, bone marrow suppression, lactic acid Poisoning and serotonin syndrome, etc.);treatment response at 6 months; | — |
Countries
China
Contacts
Public ContactDeng Guofang
Shenzhen Third People's Hospital
Outcome results
None listed