Clinical trial of treatment shortening for minimal tuberculosis in children.

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2017/07/009119
• Date of registration: 27-07-2017
• Prospective Registration: Yes
• Primary sponsor: University College London
• Public title: Clinical trial of treatment shortening for minimal tuberculosis in children.
• Scientific title: A randomized trial of therapy shortening for minimal tuberculosis with new WHO-recommended doses / fixed-dose-combination drugs in African / Indian HIV+ and HIV- children : SHINE study. - SHINE STUDY
• Date of first enrolment: 01-08-2017
• Target sample size: 1200
• Recruitment status: Open to Recruitment
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19671
• Study type: Interventional
• Study design: Randomized, Parallel Group Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Centralized Blinding and masking:Open Label
• Phase: Phase 3

Countries of recruitment

India, South Africa, Uganda, Zambia

Contacts

• Name: Dr P K Bhavani
• Affiliation: National Institute for Research in Tuberculosis

• Name: Dr Vidya Mave
• Affiliation: National Institute for Research in Tuberculosis

Key inclusion & exclusion criteria

Inclusion criteria: 1. Age 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:

a. extrathoracic lymph node TB; intra-thoracic uncomplicated (hilar) lymph node TB

b. minimal or no parenchymal abnormality on CXR

c. smear gastric aspirate/other respiratory sample (minimum 2 samples) negative

Note: GeneXpert may be positive or negative; culture of respiratory sample may be positive or negative; lymph node aspirate may be smear/culture/GeneXpert positive or negative)



5. Not previously treated for TB or successfully treated for TB > 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) 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



10. Since participants will all be under legal age of independent consent, a parent or legal guardian must be willing and able to provide informed consent. If the subject is of appropriate age, she/he will also be asked to give assent if developmentally appropriate and clinically possible.

11. Participant can comply with the protocol requirements in the opinion of the site investigator.


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, osteo articular 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



10. A clinically significant active medical condition or the presence of any concomitant severe illness or rapidly deteriorating health condition (outside of TB), which, in the opinion of the site investigator, would prevent appropriate participation in the trial, or that would make implementation of the protocol or interpretation of the study results difficult, or otherwise make the subject a poor candidate for a clinical trial.



Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Minimal Tuberculosis in Children.

Intervention(s)

Intervention1: ATT given for 4 months duration: Intensive phase 2 months of HRZE (Isoniazid H,Rifampicin R, Pyrazinamide Z, Ethambutol E) daily &
Continuation phase 2 months of HRE (Isoniazid H, Rifampicin R, Ethambutol E) daily.
Control Intervention1: ATT given for 6 months duration: Intensive phase 2 months of HRZE (Isoniazid H,Rifampicin R, Pyrazinamide Z, Ethambutol E) daily &
Continuation phase 4 months of HRE (Isoniazid H, Rifampicin R, Ethambutol E) daily.

Primary Outcome(s)

TB disease free survival 72 weeks post randomisation will be determined by the ERC and categorised as:

1. Favourable

2.Unfavourable (including death, reinfection or relapse) or

3. Not assessable (e.g. lost to follow-up)

Timepoint: 72 weeks post randomisation

Secondary Outcome(s)

1. Mortality

2. Adverse drug reactions within 30 days of completing treatment

3. Relapse/re-infection-free survival including only cases adjudicated to be TB by the independent ERC

4. Suppressed HIV viral load at 24 and 48 weeks in HIV-infected children

5. Adherence and acceptability

6. Bacterial infections (requiring hospitalisation)



Timepoint: 72 weeks post randomisation

Secondary ID(s)

ISRCTN 63579542

Version 2.1, dated 14 DEC 2015

Source(s) of Monetary Support

University College London, MRC Clinical Trials Unit, Aviation House, 125 Kingsway, London,WC2B 6NH. UK

Secondary Sponsor(s)

Government Stanley Medical College Hospital Institute of Social Pediatrics Chennai

Madras Medical College Institute of Child Health and Hospital for Children Chennai

B J Medical College and Sassoon General hospitals Pune

National Institute for Research in Tuberculosis Chennai

Ethics review

Status: Approved
Approval date: 06/05/2014
Contact:

B J Medical College & Sassoon General Hospitals

Status: Approved
Approval date: 04/05/2016
Contact:

National Institute for Research in Tuberculosis

Status: Approved
Approval date: 10/01/2017
Contact:

Madras Medical College

Status: Approved
Approval date: 28/02/2017
Contact:

Stanley Medical College