Background
Study of short regimen for MDR-TB treatment
Innovative DST technology for fluoroquinolones, SLIDs and pyrazinamide
Advanced RCT study with DST for pyrazinamide
Methods
Study regimen and comparator
Drug | Weight group | Usage | |
---|---|---|---|
≤50 kg | > 50 kg | ||
Pyrazinamide | 1500 mg daily | Once, before or after meal | |
Levofloxacin | 500 mg daily | 750 mg daily | Once, before or after meal |
Linezolid | 600 mg daily | Once, before or after meal | |
Cycloserine | 500 mg daily | 750 mg daily | Once or divide in two, before or after meal |
Clofazimine | 100 mg daily | Once, before or after meal | |
Moxifloxacin | 400 mg daily | Once, before or after meal | |
Prothionamide | 500 mg daily | 750 mg daily | Once, before or after meal |
Ethambutol | 750 mg daily | 1000 mg daily | Once, before or after meal |
Amikacin | 600 mg daily | Once, intramuscularly | |
Isoniazid | 600 mg daily | Once, before or after meal |
Site selection
Patient eligibility criteria
Detailed Description | |
---|---|
Inclusion criteria | 1) Willing to participate in trial treatment, follow-up and sign informed consent 2) Age 18–70 years old 3) Smear-positive pulmonary tuberculosis with resistance to rifampicin confirmed by Xpert® MTB/RIF (Cepheid, Sunnyvale, CA, USA) 4) Willing to carry out HIV testing 5) If a non-menopausal woman, willing to use or have used effective contraception during treatment 6) Have an identifiable address and stay in the area during the study period 7) Willing to follow the follow-up study procedure after the follow-up. |
Exclusion criteria | 1) Resistant to second-line injection confirmed by Xpert® MTB/XDR (Cepheid, Sunnyvale, CA, USA) 2) Resistant to fluoroquinolone confirmed by Xpert® MTB/XDR 3) Combined extrapulmonary tuberculosis 4) HIV antibody positive and AIDS patients 5) Severe patients and impossible to survive for more than 16 weeks according to the judgment of the research physician 6) Have been pregnant or breastfeeding 7) Unable to attend or follow treatment or follow-up time 8) Cannot take oral medications 9) Patients with impaired liver function (hepatic encephalopathy, ascites; total bilirubin is more than 2 times higher than the upper limit of normal; ALT or AST is more than 5 times the upper limit of normal) 10) Blood creatinine is more than 1.5 times the upper limit of normal 11) The investigator believes that there are any social or medical harms that expose to the participants 12) Simultaneously apply the drugs (glucocorticoids, interferons) that affect the efficacy of this study; and apply the following drugs contraindicated with the study regimens, including non-steroidal anti-inflammatory drugs, monoamine oxidase inhibitors (phenethyl hydrazine, different Carbofurs et al), direct or indirect sympathomimetic drugs (such as pseudoephedrine), vasopressor drugs (such as: adrenaline, norepinephrine), dopamine drugs (such as: dopamine, dobutamine), 5-HI reuptake inhibitor, a tricyclic antidepressant, a 5-HTI receptor antagonist (amitriptyline), meperidine or buspirone 13) Being allergic or intolerant of any study drug 14) Currently participating in another drug clinical trial 15) QTc interval ≥ 500 ms during screening 16) Hemoglobin is less than 90 g/L or platelet is less than 75*10^9/L 17) Have epilepsy, severe depression, irritability or psychosis 18) Alcohol abuse |
Recruitment process
Treatment allocation
Duration of follow-up
Sample size assumptions
Data collection and quality management
Adverse event (AE) management
External quality control of phenotypic DST
Assessment and analysis of outcome
Outcome | Description |
---|---|
Favorable outcome | • A participant’s outcome will be classified as favorable if their last two culture results are negative unless they have previously been classified as unfavorable. These two cultures must be taken on separate visits (on different days); the latest of which being within the Week 84 window (that is no more than 6 weeks before 84 weeks since randomization but with no upper bound). • Participants that don’t have a culture result within the Week 84 window because they were unable to produce sputum, will be classified as favorable if their last two cultures before the Week 84 window are negative and they have not previously been classified as unfavorable; such participants will be identified separately in tables. |
Unfavorable outcome | A participant’s outcome will be classified as unfavorable if: • They are discontinued from their allocated study treatment and subsequently restarted on a different MDR-TB regimen; • Treatment is extended beyond the scheduled end of treatment for any reason other than making up of days when no treatment was given (missed treatment) for a maximum of 8 weeks. A maximum of 14 days of extra treatment (irrespective of reason) is acceptable before it is classified as treatment extension. In addition, if the phase of treatment has been extended for delayed sputum conversion (maximum 8-week extension permitted) the scheduled end of treatment will also be extended by the same amount; • They are restarted on any MDR-TB treatment after the scheduled end of treatment, but before 84 weeks after randomization; • More than 1 drug has been changed for any reason; • They die at any point during treatment or follow-up; • At least one of their last two culture results, from specimens taken on separate occasions, is positive; |