Multidrug resistant pulmonary tuberculosis (MDR-TB) Infections and Infestations Tuberculosis
Conditions
Interventions
Current interventions as of 28/09/2011:
The study regimen (Arm B) is based on the regimen described by Van Deun 2010
it consists of moxifloxacin, clofazimine, ethambutol and pyrazinamide given for nine months (40 weeks), supplemented by kanamycin, isoniazid and prothionamide in the four months (16 weeks) of the inte
Sponsors
International Union Against Tuberculosis and Lung Disease (IUATLD, Inc.) (USA)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 25/01/2016: 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 Acid Fast Bacilli (AFB) sputum smear result at screening (at least scanty), unless they are HIV positive in which case a positive GeneXpert result within 4 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 4 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 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 use 2 methods of contraception; men who have not had a vasectomy must agree to use condoms Previous inclusion criteria: 1. Willing and able to give informed consent for treatment and follow-up (signed or witnessed consent if the patient is illiterate) 2. Aged 15 years or older, either sex 3. Has smear-positive pulmonary tuberculosis with initial laboratory result of resistance to rifampicin by line probe assay or other DST 4. Is willing to have an HIV test and if positive is willing to be treated with ART in accordance with national policies 5. Agrees to use effective barrier contraception or an intrauterine contraceptive device during treatment phase if a pre-menopausal woman 6. Has an identifiable address and expects to remain in the area for the duration of the study 7. Is willing to adhere to the follow-up schedule and to study procedures
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 25/01/2016: 1. Is infected with a strain of M. tuberculosis resistant to a second-line injectables by line probe assay 2. Is infected with a strain of M. tuberculosis resistant to a fluoroquinolone by line probe assay 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 aspartate aminotransferase (AST) or alanine aminotransferase (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 = 450 ms for stage 1, and = 500 ms for stage 2 Previous exclusion criteria from 28/09/2011 to 25/01/2016: 1. Is infected with a strain of M. tuberculosis resistant to a second-line injectable drug by line probe assay 2. Is infected with a strain of M. tuberculosis resistant to a fluoroquinolone by line probe assay 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 breastfeeding 6. Is unable to attend or comply with treatment or follow-up schedule 7. Is unable to take oral medication 8. Has AST or ALT >5 times the upper limit of normal 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 either the trial or control 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 QTc interval =500 msec at screening Original exclusion criteria: 1. Resistant to a second-line injectable drug by line probe assay 2. Resistant to a fluoroquinolone by line probe assay 3. Critically ill, and in the judgment of the investigator, unlikely to survive more than 4 months 4. Known to be pregnant or breastfeeding 5. Unable to attend or comply with treatment or follow-up schedule 6. Unable to take oral medication 7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than three times the upper limit of normal 8. Any condition (social or medical) which in the opinion of the investigator would make study participation unsafe or complicate data interpretation 9. Taking any medications contraindicated with the medicines in the study regimen 10. Known allergy to any fluoroquinolone antibiotic 11. Currently taking part in another trial of a medicinal product
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 25/01/2016: The primary efficacy outcome is the proportion of patients with a favourable outcome 132 weeks after randomisation, having not previously had an unfavourable outcome or been retreated. The primary safety outcome is the proportion of patients experiencing a grade 3 or greater adverse event during treatment and follow-up. Previous primary outcome measures from 28/09/2011 to 25/01/2016: The primary efficacy outcome is the proportion of patients with a favourable outcome 27 months after randomisation, having not previously had an unfavourable outcome or been retreated. The primary safety outcome is the proportion of patients experiencing a grade 3 or greater adverse event during treatment and follow-up. Original primary outcome measures: Measured at the end of follow-up: 1. Efficacy: proportion of patients with a favourable outcome. A patient will be classified as favourable if they have a negative culture result at the end of follow-up having not been previously classified as unfavourable. A patient will be classified as unfavourable if: 1.1. They are discontinued from treatment and restarted on MDR-TB treatment, or 1.2. They are restarted on MDR-TB treatment after the end of the treatment phase. Change of regimen for any reason other than the replacement of a single drug will result in the patient being classified as having an unfavourable outcome. In addition, the following will also be classified as unfavourable: 1.3. All deaths at any point during treatment or follow-up 1.4. A patient who has a positive culture result at the end of follow-up or if withdrawn from the study or lost to follow-up, was culture positive when last seen 2. Safety: proportion of patients experiencing a grade 3 or greater adverse event during the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 28/09/2011: 1. Time to sputum (smear and culture) conversion 2. Time to unfavourable efficacy outcome 3. Efficacy status at the end of follow-up (33 months for those with extended follow-up) 4. All-cause mortality during treatment and follow-up 5. Change of regimen for adverse drug reactions 6. Number of adverse reactions occurring on treatment 7. Adherence to treatment 8. Acceptability of regimen to all stakeholders in terms of: 8.1. Costs to the health system related to delivering the regimen and conducting follow-up tests 8.2. Household costs 8.3. Patient treatment and support experiences (frequency of health facility visits, side effects) 8.4. Health worker experiences of delivering treatment and support Previous secondary outcome measures: Measured at the end of follow-up: 1. Time to sputum culture conversion 2. Time to sputum smear conversion 3. All-cause mortality during treatment and follow-up 4. Adherence to treatment 5. Time to unfavourable efficacy outcome 6. Time to cessation of clinical symptoms 7. Cost per patient (from both health system and patient perspectives) | — |
Countries
England, Ethiopia, Mongolia, South Africa, United Kingdom, Viet Nam
Outcome results
None listed