Paediatric tuberculosis (minimal TB) Infections and Infestations Tuberculosis
Conditions
Interventions
Four-month regimen:
The experimental arm will be standard daily first-line anti-TB treatment for 16 weeks dosed according to revised WHO dosage recommendations: intensive 8 weeks Isoni
The control arm will be standard daily first-line anti-TB treatment for 24 weeks dosed according to revised WHO dosage recommendations: intensive 8 weeks HRZ(E), followed by continuation of 16 weeks
Sponsors
University College London (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 27/05/2021: 1. Aged 0-16 years 2. Weight =3kg. This has been expanded to include children weighing between 3 and 4kg; a detailed PK study of individual drugs in infants is ongoing and data using the new FDC from this study will ensure that use of this new formulation is also studied in these smallest infants. 3. Clinician has decided to treat with standard first-line regimen (intensive phase of 4 drugs or 3 drugs as per local practice) 4. symptomatic but non-severe TB including: 4.1. extrathoracic lymph node TB; intra-thoracic uncomplicated (hilar) lymph node TB 4.2. minimal or no parenchymal abnormality on CXR 4.3. smear negative on gastric aspirate/other respiratory sample Note: GeneXpert may be positive or negative and a negative GeneXpert can be used as a substitute for a negative smear; culture of respiratory sample may be positive or negative; lymph node aspirate may be smear/culture/GeneXpert positive or negative) 5. Not treated for previous TB unless successfully treated over 2 years since last completed treatment 6. Known (or pending confirmation of) HIV status; HIV-infected or HIV-uninfected 7. Willing and likely to adhere to 72 weeks follow up 8. Informed written consent from the parent/legal caregiver(s) and assent in children, as per local Ethics Committee guidance 9. Home address accessible for visiting and intending to remain within the recruitment area for follow up _____ Previous inclusion criteria: 1. Aged 0-16 years 2. Weight over 4 kg 3. Clinician has decided to treat with standard first-line regimen 4. Asymptomatic or symptomatic but non-severe TB including: 4.1. extrathoracic lymph node TB; intra-thoracic uncomplicated lymph node TB 4.2. minimal or no parenchymal abnormality on CXR 4.3. smear gastric aspirate/other respiratory sample (minimum 2 samples) negative 5. Not previously treated for TB or successfully treated for TB over 2 years since last completed treatment 6. Known HIV status; HIV-infected or HIV-uninfected 7. Willing and likely to adhere to 72 weeks follow up 8. Informed written consent from the parent/legal caregiver(s) 9. Home address accessible for visiting and intending to remain within the recruitment area for follow up
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 27/05/2021: 1. Smear-positive respiratory sample TB (note: smear-positive peripheral lymph node sample is allowed) 2. Premature (<37 weeks) and aged under 3 months 3. Miliary TB, spinal TB, TB meningitis, osteoarticular TB, abdominal TB, congenital TB 4. Pre-existing non-tuberculous disease likely to prejudice the response to, or assessment of, treatment e.g. liver or kidney disease, peripheral neuropathy, cavitation 5. Any known contraindication to taking anti-TB drugs 6. Known contact with drug resistant adult source case (including mono-resistant TB) 7. Known drug resistance in the child 8. Severely sick 9. Pregnancy _____ Previous exclusion criteria: 1. Smear-positive respiratory sample TB (note: smear-positive peripheral lymph node sample is allowed) 2. Premature (<37 weeks) and aged under 3 months 3. Miliary TB, spinal TB, TB meningitis, osteoarticular TB, abdominal TB, congenital TB 4. Pre-existing non-tuberculous disease likely to prejudice the response to, or assessment of, treatment e.g. liver or kidney disease, peripheral neuropathy, cavitation 5. Any known contraindication to taking anti-TB drugs 6. Known contact with MDR, pre-XDR or XDR adult source case 7. Proven anti-TB drug resistance in the child 8. Severely sick 9. Pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Efficacy: Unfavourable outcome, defined by the composite endpoint of TB treatment failure, relapse (or re-infection) or death 2. Safety: Grade 3/4 adverse events | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 27/05/2021: 1. Mortality 2. Adverse drug reactions up to 30 days of completing treatment 3. Unfavourable outcome in those with definite TB as adjudicated by the ERC 4. Suppressed HIV viral load at 24 and 48 weeks in HIV infected children 5. Adherence and acceptability 6. Bacterial infections (requiring hospitalisation) _____ Previous secondary outcome measures: 1. Mortality 2. Adverse drug reactions up to 30 days of completing treatment 3. Unfavourable outcome in those with definite TB 4. Suppressed HIV viral load at 24 and 48 weeks in HIV infected children starting ART, measured centrally on stored samples 5. Adherence and acceptability 6. Bacterial infections | — |
Countries
England, India, South Africa, Uganda, United Kingdom, Zambia
Outcome results
None listed