Pre-extensively drug resistant tuberculosis (pre-XDR TB) Infections and Infestations
Conditions
Interventions
Intervention arm regimen: BDLC
Participants in the intervention arm will receive the BDLC regimen, which includes:
• Bedaquiline: 400 mg once daily for 2 weeks, then 200 mg three times per week for th
Sponsors
Association for Social Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 14 years or older at the time of diagnosis. Patients younger than 14 will be excluded and managed according to national guidelines. 2. Provides informed consent to participate in the study and attend follow-up visits. If the patient is illiterate, consent must be obtained through a witnessed process (signed or thumb-printed). 3. Has bacteriologically or molecularly confirmed tuberculosis (TB) with documented resistance to at least rifampicin and a fluoroquinolone, as identified through rapid molecular testing and/or conventional culture-based drug susceptibility testing (DST). 4. Has no known contraindication to the use of drugs in the study regimens (BPaL or BDLC), and is medically fit to receive second-line anti-TB treatment. 5. Is able to take oral medications and adhere to the treatment and follow-up schedule under programmatic management of drug-resistant TB (PMDT) conditions.
Exclusion criteria
Exclusion criteria: 1. Drug susceptibility testing (DST) shows fluoroquinolone sensitivity, or DST results are not yet available at baseline. 2. Inability to take oral medication due to clinical or functional limitations (e.g., severe gastrointestinal conditions, swallowing difficulty). 3. Known hypersensitivity or allergy to one or more drugs in the study regimens (BPaL: bedaquiline, pretomanid, linezolid; BDLC: bedaquiline, delamanid, linezolid, clofazimine). 4. Baseline QTcF interval =500 milliseconds, which is not correctable with medical management, as confirmed by ECG. 5. Concurrent use of medications that are contraindicated with any drugs included in the study regimens, and which cannot be safely discontinued or substituted. 6. Pregnant or breastfeeding at the time of enrolment, due to insufficient safety data for study drugs during pregnancy and lactation. 7. Severe baseline organ dysfunction, including: 7.1. Liver dysfunction: ALT or AST > 5 times the upper normal limit. 7.2. Renal impairment: Serum creatinine > 2 times the upper normal limit, or creatinine clearance < 50 mL/min.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of pre-extensively drug resistant tuberculosis (pre-XDR TB) patients with a successful treatment outcome, defined as “cured” or “treatment completed” at the end of treatment (6 to 9 months), based on National TB Program definitions measured using patient records | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Mortality during treatment is measured using programmatic records and death certificates at any time during the treatment period 2. Loss to follow-up is measured using treatment records and defined as treatment interruption for 2 consecutive months or more at any time during the treatment period 3. Treatment failure is measured using bacteriological and clinical criteria defined in the study protocol, including sputum culture results and clinical assessments, at 4 months and end of treatment 4. Adherence to treatment is measured using treatment cards and adherence records as the proportion of prescribed doses taken, assessed monthly throughout the treatment period 5. Adverse events of special interest are measured using clinical assessments and laboratory tests recorded in the DR-TB 01 form at baseline and monthly during treatment 6. Health-Related Quality of Life (HRQoL) is measured using the EQ-5D-5L questionnaire at baseline and at the end of treatment 7. Time to sputum culture conversion is measured using monthly sputum cultures until two consecutive negative cultures at least 30 days apart are obtained 8. Post-treatment recurrence is measured using clinical and bacteriological assessments during optional follow-up visits at ... 9. Incremental cost of delivering BDLC compared to BPaL is measured using cost data on drugs, diagnostics, personnel, adverse event management, and hospitalization from provider records at the end of the treatment period | — |
Countries
Pakistan
Contacts
Public ContactMuhammad Ahmar Khan
Outcome results
None listed