Health Condition 1: null- MDR-TB or Rif resistant cases Health Condition 2: A150- Tuberculosis of lung
Conditions
Interventions
Intervention1: Regimen A: WHO-approved MDR-TB regimen
Intervention2: regimen C: 40-week all-oral regimen consisting of bedaquiline, clofazimine, ethambutol, levofloxacin, and pyrazinamide given for 40
Sponsors
The international Union Against Tuberculosis and lung diseases
Eligibility
Inclusion criteria
Inclusion criteria: A patient will be eligible for randomisation into the study (Stage 2) if he/she: 1. Is willing and able to give informed consent to participate in the trial treatment and follow-up (signed or witnessed consent if the patient is illiterate) 2. Is aged 18 years or older 3. Has a positive AFB sputum smear result at screening (at least scanty), unless they are HIV positive in which case a positive GeneXpert result within four weeks prior to screening is sufficient 4. Has evidence of resistance to rifampicin either by line probe assay (Hain Genotype21), GeneXpert or culture-based drug susceptibility testing (DST), from a test performed at screening or from a test performed within the four weeks prior to screening 5. Is willing to have an HIV test and, if positive, is willing to be treated with ART in accordance with the national policies but excluding ART contraindicated for use with bedaquiline 6. Is willing to use effective contraception: pre-menopausal women or women whose last menstrual period was within the preceding year, who have not been sterilised must agree to use a barrier method or an intrauterine device unless their partner has had a vasectomy; men who have not had a vasectomy must agree to use condoms. In Stage 2 pre-menopausal women or women whose last menstrual period was within the preceding year, who have not been sterilised must agree to use two methods of contraception, for example a hormonal method and a barrier method. 7. Resides in the area and expected to remain for the duration of the study. 8. Has had a chest X-ray at that is compatible with a diagnosis of pulmonary TB (if such a chest X-ray taken within 4 weeks of randomisation is available, a repeat X-ray is not required) 9. Has normal K+, Mg2+ and corrected Ca2+ at screening.
Exclusion criteria
Exclusion criteria: A patient will not be eligible for randomisation into the study ( Stage 2) if he/she: 1.Is infected with a strain of M. tuberculosis resistant to a second-line injectables by line probe assay (Hain Genotype21) 2.Is infected with a strain of M. tuberculosis resistant to a fluoroquinolone by line probe assay (Hain Genotype21) 3.Has tuberculous meningitis or bone and joint tuberculosis 4.Is critically ill, and in the judgment of the investigator, unlikely to survive more than 4 months 5.Is known to be pregnant or breast-feeding 6.Is unable or unwilling to comply with the treatment, assessment, or follow-up schedule 7.Is unable to take oral medication 8.Has AST or ALT more than 5 times the upper limit of normal for Stage 1, and AST or ALT more than 3 times the upper limit of normal for Stage 2 9.Has any condition (social or medical) which in the opinion of the investigator would make study participation unsafe 10.Is taking any medications contraindicated with the medicines in any trial regimen 11.Has a known allergy to any fluoroquinolone antibiotic 12.Is currently taking part in another trial of a medicinal product 13.Has a QT or QTcF interval at screening or immediately prior to randomisation of more than or equal to 500 ms for Stage 1, and more than or equal to 450 ms for Stage 2. 14. Has experienced one or more of the following risk factors for QT prolongation: ââ?¬Â¢ A confirmed prolongation of the QT or QTcF more than or equal to 450 ms in the screening ECG (retesting to reassess eligibility will be allowed once using an unscheduled visit during the screening phase) ââ?¬Â¢ Pathological Q-waves (defined as Q-wave more than 40 ms or depth more than 0.4-0.5 mV) ââ?¬Â¢ Evidence of ventricular pre-excitation (e.g., Wolff Parkinson White syndrome) ââ?¬Â¢ Electrocardiographic evidence of complete or clinically significant incomplete left bundle branch block or right bundle branch block ââ?¬Â¢ Evidence of second or third degree heart block ââ?¬Â¢ Intraventricular conduction delay with QRS duration more than 120 ms ââ?¬Â¢ Bradycardia as defined by sinus rate less than 50 bpm ââ?¬Â¢ Personal or family history of Long QT Syndrome ââ?¬Â¢ Personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, with the exception of sinus arrhythmia ââ?¬Â¢ Syncope (i.e. cardiac syncope not including syncope due to vasovagal or epileptic causes) ââ?¬Â¢ Risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, or hypomagnesemia) 15.Has received treatment for MDR-TB in the 12 weeks prior to screening, other than the maximum permitted treatment 16.Has a history of cirrhosis and classified as Childââ?¬•s B or C at screening or a bilirubin more than 1.5 times upper limit of normal. 17.Has an estimated creatinine clearance (CrCl) less than 30 mL/min based on the Cockcraft-Gault equation 18.Is HIV positive and has a CD4 count less than 50 cells/mm3 19.Has amylase elevation more than two times above the upper limit of normal 20.Has a history of alcohol and/or drug abuse 21.Has had previous treatment with bedaquiline 22.Has taken rifampicin in the seven days prior to randomisation 23.There has been a delay of more than four weeks between the scre
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Favourable Last two culture (two separate visits, one within 6 weeks of Rx completion) results are negative unless they have previously been classified as unfavourable Unfavourable Failure , Discontinued, restarted on different regimen, death, extension of treatment from allocated study treatment and subsequently restarted on a different MDR-TB regimen other than a single drug substitution Timepoint: 76 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| sputum smear and culture conversion, cessation of clinical symptoms , drug modification /substitution,grade 3 or 4 adverse reactions, Adherence to treatmentTimepoint: baseline to 132 weeks | — |
Countries
Georgia, India, Indonesia, Mongolia, South Africa, Uganda, Viet Nam
Contacts
Public ContactDrGNarendran For India
National institute for Research in Tuberculosis, ICMR
Outcome results
None listed