| CTRI Number |
CTRI/2017/07/009119 [Registered on: 27/07/2017] Trial Registered Prospectively |
| Last Modified On: |
04/08/2017 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Clinical trial of treatment shortening for minimal tuberculosis in children. |
|
Scientific Title of Study
|
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. |
| Trial Acronym |
SHINE STUDY |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| ISRCTN 63579542 |
ISRCTN |
| Version 2.1, dated 14 DEC 2015 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr S Syed Hissar |
| Designation |
Scientist C |
| Affiliation |
National Institute for Research in Tuberculosis |
| Address |
Room No. 209, Department of Clinical Research,
National Institute for Research in Tuberculosis,
No.1, Mayor Sathyamoorthy Road,
Chetpet, Chennai
Chennai
TAMIL NADU
600031
India |
| Phone |
|
| Fax |
|
| Email |
drsyed@rediffmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr P K Bhavani |
| Designation |
Scientist D |
| Affiliation |
National Institute for Research in Tuberculosis |
| Address |
Room No. 207, Department of Clinical Research,
National Institute for Research in Tuberculosis,
No.1, Mayor Sathyamoorthy Road,
Chetpet, Chennai
Chennai
TAMIL NADU
600031
India |
| Phone |
|
| Fax |
|
| Email |
bhavani.pk@nirt.res.in |
|
Details of Contact Person
Public Query
|
| Name |
Dr Vidya Mave |
| Designation |
CRS Leader and Director, BJMC CTU |
| Affiliation |
B J Medical College and Sassoon General hospitals |
| Address |
1st floor, Clinical Trials Unit, Pathology Museum,
B J Medical College and Sassoon General hospitals,
Jai Prakash Narayan road,
Pune
Pune
MAHARASHTRA
411001
India |
| Phone |
|
| Fax |
|
| Email |
vidyamave@gmail.com |
|
|
Source of Monetary or Material Support
|
| University College London,
MRC Clinical Trials Unit,
Aviation House, 125 Kingsway,
London,WC2B 6NH. UK |
|
|
Primary Sponsor
|
| Name |
University College London |
| Address |
MRC Clinical Trials Unit,
Aviation House, 125 Kingsway,
London,WC2B 6NH. UK
|
| Type of Sponsor |
Research institution |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| B J Medical College and Sassoon General hospitals Pune |
B J Medical College and Sassoon General hospitals,
Jai Prakash Narayan road, Pune 411001.
|
| Government Stanley Medical College Hospital Institute of Social Pediatrics Chennai |
Government Stanley Medical College & Hospital,
Institute of Social Pediatrics, Chennai 600001.
|
| Madras Medical College Institute of Child Health and Hospital for Children Chennai |
Madras Medical College, Institute of Child Health and Hospital for Children, Chennai 600003. |
| National Institute for Research in Tuberculosis Chennai |
National Institute for Research in Tuberculosis,
No.1, Mayor Sathyamoorthy Road,
Chetpet, Chennai 600031,
Tamil Nadu, India.
|
|
|
Countries of Recruitment
|
Uganda
India
South Africa
Zambia |
|
Sites of Study
|
| No of Sites = 4 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Arathi Kiniker |
B.J. Government Medical College and Sassoon General Hospital |
1st floor, Clinical Trials Unit, Pathology Museum,
Jai Prakash Narayan Road,
Pune 411001
Pune
MAHARASHTRA |
9850039063
aarti.kinikar63@gmail.com |
| Dr B Sarath Balaji |
Madras Medical College |
Room No. 2, Department of Pulmonology OP,
Institute of Child Health (ICH) and Hospital for Children,
Egmore,Chennai 600008
Chennai
TAMIL NADU |
9443697844
sarath1731@yahoo.co.in |
| Dr S Syed Hissar |
National Institute for Research in Tuberculosis |
Room No. 209, Department of Clinical Research,
No.1, Mayor Sathyamoorthy Road,
Chetpet, Chennai 600031.
Chennai
TAMIL NADU |
9442927242
drsyed@rediffmail.com |
| Dr M A Aravind |
Stanley Medical College |
3rd floor, Department of Pediatrics, Institute of Social Pediatrics Royapuram, Chennai 600001
Chennai
TAMIL NADU |
9840242328
aravindma2003@yahoo.co.in |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 4 |
| Name of Committee |
Approval Status |
| B J Medical College & Sassoon General Hospitals |
Approved |
| Madras Medical College |
Approved |
| National Institute for Research in Tuberculosis |
Approved |
| Stanley Medical College |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Minimal Tuberculosis in Children. , |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
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. |
| Comparator Agent |
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. |
|
|
Inclusion Criteria
|
| Age From |
1.00 Day(s) |
| Age To |
16.00 Year(s) |
| Gender |
Both |
| Details |
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.
|
|
| ExclusionCriteria |
| Details |
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.
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
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)
|
72 weeks post randomisation |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
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)
|
72 weeks post randomisation |
|
|
Target Sample Size
|
Total Sample Size="1200"
Sample Size from India="450"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
01/08/2017 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
01/07/2016 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="4"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
None Yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
This study
is a randomized, open label, parallel arm, phase III clinical trial of therapy shortening
for minimal tuberculosis with new WHO-recommended doses/ fixed-dose-combination
drugs in African and Indian HIV+ and HIV- children below 16 years of age. The
primary outcome measures will be unfavorable
outcomes: TB treatment failure, relapse (or re-infection) or death and adverse
events. The secondary outcome measures will be mortality, adverse drug reactions
up to one month of completing treatment, suppressed HIV viral load at specified
time points in HIV infected children. |