ISRCTN63579542.

Trial name or title	Shorter treatment for minimal tuberculosis in children (SHINE study)
Methods	Parallel‐group, randomized, non‐inferiority, open‐label, 2‐arm, phase 3 clinical trial
Participants	Inclusion criteria: Age 0 to 16 years Weight > 4 kg Clinician has decided to treat with standard first‐line regimen Asymptomatic or symptomatic but with non‐severe tuberculosis including not previously treated for tuberculosis or successfully treated for tuberculosis over 2 years since last completed treatment Known HIV status: HIV infected or HIV uninfected Willing and likely to adhere to 72 weeks of follow‐up Informed written consent from parent/legal caregiver Home address accessible for visiting and intending to remain within recruitment area for follow‐up Exclusion criteria: Smear positive respiratory sample tuberculosis Premature (< 37 weeks) and aged under 3 months Miliary tuberculosis, spinal tuberculosis, tuberculosis meningitis, osteoarticular tuberculosis, abdominal tuberculosis, congenital tuberculosis Pre‐existing liver or kidney disease, peripheral neuropathy, cavitation Any known contraindication to taking anti‐tuberculosis drugs Known contact with MDR, pre‐XDR, or XDR adult source case Proven anti‐tuberculosis drug resistance in the child Severely sick Pregnancy Anticipated sample size: 1200
Interventions	Intervention: 4‐month standard ATT regimen 8 weeks intensive Isoniazid (H), rifampicin (R), pyrazinamide (Z) with or without ethambutol (E) according to local practice, HRZ(E), followed by 8 weeks of continuation HR Control: 6‐month standard ATT regimen 8 weeks intensive HRZ(E), followed by 6 weeks of continuation HR
Outcomes	Primary outcome measures: • Efficacy: unfavourable outcome, defined by the composite endpoint of tuberculosis treatment failure, relapse (or re‐infection), or death • Safety: grade 3/4 adverse events Secondary outcome measures: • Mortality • Adverse drug reactions up to 30 days of completing treatment • Unfavourable outcome in those with definite tuberculosis • Suppressed HIV viral load at 24 and 48 weeks in HIV‐infected children starting ART, measured centrally on stored samples • Adherence and acceptability • Bacterial infection Anciliary studies will evaluate pharmacokinetics; cost/cost‐effectiveness implications of treatment shortening, and a nested qualitative substudy will investigate the ways in which health workers manage implementation of dose and weight band recommendations, particularly in children taking anti‐tuberculosis drugs and ARVs
Starting date	April 2015; anticipated end date: April 2019 (no longer recruiting)
Contact information	SHINE Trial Management Team MRC Clinical Trials Unit at UCL Institute of Clinical Trials and Methodology Aviation House, 125 Kingsway, London WC2B 6NH, UK Ph: +44 (0) 20 7670 4700 Email: SHINE.MRCCTU@ucl.ac.uk
Notes	Study locations: South Africa, India, Uganda, Zambia Registration number:ISRCTN63579542 Primary sponsors: University College London, Joint Global Health Trials Scheme: Department for International Development, the Wellcome Trust, the Medical Research Council, and Svizera Ltd