Tuberculosis
Conditions
Interventions
Study Strategy
Sponsors
Wits Health Consortium
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to give informed consent to be enrolled in the research study prior to any study related procedures (signed or witnessed consent if the participant is unable to read and understand the informed consent document; signed or witnessed consent from a child's biological parent, legal guardian or primary caregiver) and if the participant is a child (6-17 years) is willing to sign assent 2. Willing and able to adhere to the complete follow-up schedule and to study procedures 3. Male or female, aged 6 years or older, including breastfeeding and/or pregnant women 4. Weigh more than or equal to 16kg 5. Participants above the age of 12 years, must have confirmed pulmonary TB with initial laboratory result of resistance to at least rifampicin as confirmed by genotypic or phenotypic susceptibility testing in the last three months 6. Willing to use effective contraception for females of childbearing potential if sexually active; must be willing to use either an intrauterine contraceptive device or a hormonal method for the duration of the treatment regimen and for three months thereafter 7. Willing to have an HIV test, and if positive, is willing to be treated with appropriate antiretroviral therapy 8. Participants between the ages of 6 – 12 years, must have either confirmed pulmonary RR-TB or probable pulmonary RR-TB and a decision has been made by the referring clinician or investigator to treat the child for RR-TB 9. Participants who are pregnant, should have an ultrasound done to confirm a viable intrauterine pregnancy prior to enrolment
Exclusion criteria
Exclusion criteria: 1.Had taken more than 28 days but less than 24 weeks of second line TB drugs including BDQ, LNZ, CFZ, fluoroquinolones or DLM. Please note: Participants with prior successfully treated episodes of DR TB are permitted to enroll. 3. Has complicated or severe extra-pulmonary manifestations of TB, including osteo-articular, pericardial and central nervous system infection as per investigators opinion. 4. Is unable to take oral medication. 5. Is taking any prohibited medications as referred to in the protocol. 6. Has a known allergy or hypersensitivity to any of the medicines in the regimens. 7. Is currently taking part in another clinical trial of any medicinal product. 8. Has a QTcF interval of greater than 480 ms. Please note: If the QTcF interval is greater than 480 ms, it may be repeated if participant has reversible contributory factors, i.e. low potassium or to allow washout of previous QT prolonging drugs. 9. Has clinically significant ECG abnormality in the opinion of the site investigator within 60 days prior to entry, including but not limited to second or third degree atrioventricular (AV) block or clinically important arrhythmia. 10.Participants with the following laboratory abnormality at screening: a) Haemoglobin level of 2.0 x ULN, or >1.50 x ULN when accompanied by any increase in other liver function test g) Serum potassium less than 3.2 mmol/l 11.Peripheral neuropathy of grade 3 or 4 using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 12. If in the investigator's opinion, the participant is unable to commit to study related procedures or it is unsafe for participant to take part in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of participants with a successful outcome at the end of follow up at 76 weeks post treatment initiation A successful end of follow up outcome measured at 76 weeks post treatment initiation is defined as either Cured or Culture negative when last seen. Cured: Sputum Culture negative at the end of follow up at 76 weeks post treatment initiation. Culture negative when last seen: if the participant is lost before the end of follow up at 76 weeks and provided they have a successful treatment outcome at the last study visit attended.;The proportion of participants who experience grade 3 or greater adverse events during treatment and up to 30 days following the end of treatment Adverse events are graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events;The proportion of participants with a successful outcome at the end of treatment. A successful treatment outcome measured at the end of treatment is defined as either Cured or Treatment Completed. Cured: Adequate treatment adherence (at least 80% of doses taken) as per protocol without evidence of failure AND the last two negative sputum specimens at the end of treatment being culture negative. These specimens must be separated by at least 14 days. Treatment completed: Adequate treatment adherence (at least 80% of doses taken) as per protocol without evidence of failure BUT no record that two or more consecutive cultures taken at least 14 days apart are negative. | — |
Secondary
| Measure | Time frame |
|---|---|
| The proportion of participants with a successful composite outcome at 76 weeks post treatment initiation A successful composite outcome is defined as a successful end of follow up outcome at 76 weeks post treatment initiation and no grade 3 or higher adverse events during treatment. A successful end of follow up outcome is either Cured or Culture negative when last seen.;Development of a population PK model of clofazimine exposure;Estimation of individual participant drug exposures for bedaquiline, delamanid, levofloxacin, and linezolid from sparse data using existing population PK models;Determination of PK-PD relationships of toxicity (QT prolongation and increase in ALT from baseline) using estimated individual participant drug exposures of drugs/metabolites known to cause QT prolongation (clofazimine, bedaquiline M2 metabolite, delamanid DM6705 metabolite, and levofloxacin);Determination of PK-PD relationships of linezolid toxicity (bone marrow suppression, peripheral neuropathy, and optic neuritis);Determination of the change in the intervention strategy of free concentrations of bedaquiline, delamanid, levofloxacin, and linezolid over the first 8 weeks of therapy in a sub-group;Determination of PK-PD relationships of efficacy (using change in time to sputum culture positivity as the efficacy parameter) in the intervention strategy of bedaquiline, delamanid, levofloxacin, and linezolid | — |
Countries
South Africa
Contacts
Public ContactHannelise Feyt
Wits Health Consortium
Outcome results
None listed