Condition category
Infections and Infestations
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Of the estimated 9 million tuberculosis (TB) cases globally annually, more than half a million are in children. This burden is highest in Africa and South East Asia and results in 100,000 deaths each year.
Regimens for prevention and treatment of TB in children have lagged considerably behind those for adults. This is likely because children usually present with 'minimal' (i.e. smear-negative and less severe) disease. Therefore TB in children is very difficult to diagnose and children are rarely infectious, posing little risk of onward transmission. Current TB treatment (for both adults and children) involves six months of treatment: a two month intensive phase of three or four drugs, followed by a maintenance phase lasting four months. Historically, the doses of drugs prescribed to children have been based on a weight-based scaling-down of the adult dose, resulting in uncertainty over the correct paediatric dose.
In 2010, the WHO revised their dose recommendations for anti-TB drugs for children, and now recommends higher doses of many of the commonly used drugs. Based on this dose increase, the SHINE study wants to find out if the standard 6 month regimen can be reduced to 4 months.

Who can participate?
Children under 16 with suspected minimal TB disease (with or without HIV infection) will be screened. A total of 1,200 children will be recruited.

What does the study involve?
A screening visit involving TB tests (skin test and sputum sample), an X-ray and blood tests will be carried out to confirm that the child is eligible. Consenting participants will then be randomly allocated to either the 4-month regimen or the 6-month regimen. Enough anti-TB drugs will be prescribed for the child to take daily until they are seen at their next clinic visit. Visits will be monthly whilst taking the medication, and then every three months. At each visit, details of the child's health, height and weight will be recorded, as well as information about how well children take their medicines and if there are any particular problems taking them. At some visits, blood, urine and hair samples will be collected for storage and future testing.

What are the possible benefits and risks of participating?
There may be no direct benefit to the children participating in the SHINE study. However, the information we get from this study will help to improve treatment for children with TB in the future.
These children need to be treated for TB regardless of whether or not they participate in the SHINE study, and treatment has risks and side effects. The common side effects of anti-TB drugs are red tears, red urine, joint pains and injury to the liver. Participating children will also need to attend the clinic more frequently than if they were receiving treatment outside of the SHINE study. In addition there will be some extra blood tests.

Where is the study run from?
4 sites:
- South Africa: Stellenbosch University, Cape Town (target recruitment: 250 children)
- India: National Institute for Research in Tuberculosis, Chennai and BJ Medical College, Pune (target recruitment: 450 children)
- Uganda: MU-JHU Care Ltd, Kampala (target recruitment: 250 children)
- Zambia: University Teaching Hospital, Lusaka (target recruitment: 250 children)
Coordinated from MRC Clinical Trials Unit at UCL, London, UK.

When is the study starting and how long is it expected to run for?
The total duration of the study will be 48 months, as follows: 6 months start-up, 18 months enrolment, follow-up until the last patient has reached 18 months, and a further 6 months for close-out and analysis.
- Anticipated start date of recruitment: Q2 2015.
- Anticipated end date of recruitment: Q4 2016.
- Anticipated study end date: Q2 2019.

Who is funding the study?
SHINE is funded by the Joint Global Health Trials Scheme: Department for International Development, the Wellcome Trust, the Medical Research Council and Svizera Ltd.

Who is the main contact?
SHINE Trial Management Team
MRC Clinical Trials Unit at UCL
Institute of Clinical Trials and Methodology
Aviation House, 125 Kingsway, London WC2B 6NH, UK
+44 (0) 20 7670 4700

Trial website

Contact information



Primary contact

Prof Diana Gibb


Contact details

MRC Clinical Trials Unit at UCL
Institute of Clinical Trials & Methodology
Aviation House
125 Kingsway
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

A randomised trial of therapy shortening for minimal tuberculosis with new WHO-recommended doses/ fixed-dose-combination drugs in African and Indian HIV-positive and HIV-negative children



Study hypothesis

The 4-month regimen will be non-inferior to the 6-month regimen in terms of unfavourable outcomes at 72 weeks.

Ethics approval

Lead centre: UCL Research Ethics Committee; 22/05/2014; 5669/001

1. South Africa: Stellenbosch Research Ethics Committee and University of Cape Town Human Research Ethics Committee
2. India: National Institute for Research in Tuberculosis Institutional Ethics Committee and B J Medical College & Sassoon General Hospitals Ethics Committee
3. Uganda: Joint Clinical Research Center Institutional Review Board
4. Zambia: University of Zambia- Biomedical Research Ethics committee

Study design

Parallel-group randomised non-inferiority open label 2-arm phase III clinical endpoint trial

Primary study design


Secondary study design

Randomised parallel trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Paediatric tuberculosis (minimal TB)


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 Isoniazid (H) , Rifampicin (R), Pyrazinamide (Z) with or without Ethambutol (E) according to local practice, HRZ(E), followed by continuation of 8 weeks HR.

Six-month regimen;
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 HR.

Intervention type



Phase III

Drug names

Isoniazid (H) , Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E)

Primary outcome measure

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 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

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Aged 0-16
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

Participant type


Age group




Target number of participants


Participant 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

Recruitment start date


Recruitment end date



Countries of recruitment

India, South Africa, Uganda, Zambia

Trial participating centre

MRC Clinical Trials Unit at UCL
United Kingdom

Sponsor information


University College London (UK)

Sponsor details

Gower Street
United Kingdom

Sponsor type




Funder type


Funder name

Department for International Development (DFID) (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

Wellcome Trust

Alternative name(s)


Funding Body Type

private sector organisation

Funding Body Subtype



United Kingdom

Funder name

Medical Research Council (MRC) (UK) grant number MR/L004445/1

Alternative name(s)


Funding Body Type

government organisation

Funding Body Subtype

National government


United Kingdom

Funder name

Svizera Ltd. (India) - Anti-tuberculosis trial drugs

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes