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Trial registered on ANZCTR


Registration number
ACTRN12622000115730
Ethics application status
Approved
Date submitted
23/10/2021
Date registered
24/01/2022
Date last updated
24/01/2022
Date data sharing statement initially provided
24/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Test and Treat to End Tuberculosis (TB): A screening and treatment study for children and adults with Latent Tuberculosis Infection (LTBI)
Scientific title
Test and Treat to End Tuberculosis (TB): Investigating the effect of a screening for, and treatment of, latent TB infection (LTBI) in the general population on the prevalence of TB in that population.
Secondary ID [1] 305460 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
ACT5 (Active Case finding for TB, 5th study)
Linked study record
ACTRN12619001439134. This was the pilot study that preceded and informed this current study.

Health condition
Health condition(s) or problem(s) studied:
Latent Tuberculosis Infection 323839 0
tuberculosis 323924 0
Condition category
Condition code
Respiratory 321347 321347 0 0
Other respiratory disorders / diseases
Infection 321348 321348 0 0
Other infectious diseases
Public Health 321931 321931 0 0
Epidemiology
Public Health 321932 321932 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
TEST phase: Screening for LTBI infection
TREAT phase: Treatment of LTBI in those who screen positive for LTBI.

TEST
Screening for LTBI will be performed as the part if the study. Screening involves implementation of an tuberculin skin test (TST) using the Mantoux technique. A TST involves a small injection of tuberculin into the forearm. After 48-96 hours the injection site is assessed for any reaction (lump).

Those with a positive TST will have a chest x-ray performed and a sputum specimen collected to screen for active TB disease. If active TB is diagnosed the person will be referred for treatment of TB. If active TB is not found, the person will be offered treatment for LTBI.

TREAT
People with LTBI who do not have active TB and do not meet specified exclusion criteria, will be offered treatment for LTBI with the 3HP regimen: 12 weeks of oral treatment administered once a week with isoniazid (900mg if greater than or equal to 50Kg) and rifapentine (900mg if greater than or equal to 50Kg) with sliding scale lower weight based doses for children aged between 5 years and 15 years of age weighing less than 50Kg.
Wherever possible the participant will ingest the medication in front of the researcher. When this is not possible, questions about adherence will be asked by telephone or face to face interview. The treatment is administered in the form of an oral tablet.
Intervention code [1] 321861 0
Early detection / Screening
Intervention code [2] 321932 0
Treatment: Drugs
Comparator / control treatment
There will be no specific intervention by the research team in the comparator/control clusters. People in these clusters will be managed by the health sector staff in accordance with usual care under the direction of the Ministry of Health. As the active intervention here is a community-wide case finding (screening) intervention, there is no equivalent intervention for the control/comparator group. Cases of TB will be diagnosed through the routine health care system. There is no systematic screening for TB or LTBI in Vietnam - hence, this will not be implemented in the control/comparator clusters. .
Control group
Active

Outcomes
Primary outcome [1] 329133 0
Population prevalence of bacteriologically-confirmed Tuberculosis (TB). This is will be estimated in a cross-survey of the general population aged 15 years and over. A bacteriologiically-confirmed case will be defined as a case in whom a sputum specimen tests positive on Xpert MTB Ultra (a nucleic acid amplification test) or on mycobacterial culture with subsequent identification as M tuberculosis.
Timepoint [1] 329133 0
A minimum of two years after commencement of the intervention
Secondary outcome [1] 401572 0
To estimate the incidence of severe adverse events attributable to the intervention. This will be assessed by clinical data review by an Expert Clinical Panel. They will have access to blood tests including liver function tests,
Timepoint [1] 401572 0
A minimum of two years after commencement of the intervention
Secondary outcome [2] 401573 0
To estimate the effect of the intervention on all-cause mortality;
Timepoint [2] 401573 0
A minimum of two years after commencement of the intervention
Secondary outcome [3] 401575 0
To estimate the prevalence of latent TB infection among children born between 2008 and 2016 this will be determined using the QuantiFERON®-TB Gold Plus test kit.
Timepoint [3] 401575 0
A minimum of four years after commencement of the intervention

Eligibility
Key inclusion criteria
Eligibility criteria for TEST phase
1. Aged 5 years or older on the date of enumeration; AND
2. Capable of giving informed consent or, if aged < 15 years, having a parent or guardian who can give consent. Assent will also be routinely sought from children aged 10 to <15 years; AND
3. Not currently taking treatment for tuberculosis.
Eligibility criteria for TREAT phase
1. Meet eligibility criteria for testing and consented to screening; AND
2. Tuberculin skin test (TST) reaction size >= 10mm (or > 0mm if known to be HIV +ve) AND
3. Either no abnormality consistent with TB on chest radiograph OR abnormal radiograph but two sputum specimens are culture negative for M. tuberculosis
Minimum age
5 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Pregnant or planning to be pregnant in next 6 months
2. Important potential drug interactions with the intervention regimen, defined by attending medical officer in accordance with a schedule.
3. Known allergy or hypersensitivity to the active substance or any of the ingredients of the study drugs
4. Has completed a course of treatment for TB within the preceding two years.
5. Serum transaminases (AST and ALT) are both >= 3 x upper limit of normal
6. Severe or life-threatening illness that is considered by the attending medical officer to make treatment for LTBI inappropriate.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The sampling unit will be the sub-commune (known as ‘Ap’, roughly equivalent to a village, suburb or hamlet) with an average population of ~ 1,000 persons aged 15 and over. Sub-communes are grouped in communes, which are grouped in districts.
The number of sub-communes available for participation in this study, after the exclusion of sub-communes previously used in the ACT3 study, was 763. From the 763 sub-communes, we will randomly select, using computer-generated random numbers, the required number of sub-communes stratified by district and with a probability proportional to population size. The selected sub-communes will then be randomly assigned to active vs control status, using computer-generated random numbers, again stratified by district and by population size. This will ensure both representative selection and balanced allocation of sub-communes from within the district.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
This design is an open-label, parallel-group, cluster-randomised controlled trial
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
The analysis will be by intention to treat. We will use a two level, hierarchical generalised linear model with a Poisson error distribution to test the effect of treatment group allocation on number of prevalent cases of pulmonary TB in persons aged greater than or equal to 15 years. Treatment group allocation will be the main (fixed) effect. Clusters will be treated as a random intercept term. The enumerated cluster population aged greater than or equal to 15 years will be the offset. A p value < 0.05 will be treated as significant. No covariates will be included in the primary analysis. Prevalence rate ratios will be estimated with 95% confidence intervals, adjusted for clustering.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
4/04/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
208000
Accrual to date
Final
Recruitment outside Australia
Country [1] 24163 0
Viet Nam
State/province [1] 24163 0
Ca Mau

Funding & Sponsors
Funding source category [1] 309818 0
Government body
Name [1] 309818 0
National Health and Medical Research Council
Country [1] 309818 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Woolcock Institute of Medical Research
Address
431 Glebe Point Road
Glebe, NSW, 2037
Country
Australia
Secondary sponsor category [1] 310852 0
None
Name [1] 310852 0
Address [1] 310852 0
Country [1] 310852 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309561 0
The University of Sydney, Human Research Ethics Committee
Ethics committee address [1] 309561 0
Ethics committee country [1] 309561 0
Australia
Date submitted for ethics approval [1] 309561 0
28/04/2021
Approval date [1] 309561 0
21/09/2021
Ethics approval number [1] 309561 0
2021/412

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114594 0
Prof Guy B Marks
Address 114594 0
Woolcock Institute of Medical Research
Box M77 Missenden Road Post Office
Camperdown, NSW, 2050
Country 114594 0
Australia
Phone 114594 0
+61 419251565
Fax 114594 0
+61291140011
Email 114594 0
g.marks@unsw.edu.au
Contact person for public queries
Name 114595 0
Guy B Marks
Address 114595 0
Woolcock Institute of Medical Research
Box M77 Missenden Road Post Office
Camperdown, NSW, 2050
Country 114595 0
Australia
Phone 114595 0
+61 419251565
Fax 114595 0
+61291140011
Email 114595 0
g.marks@unsw.edu.au
Contact person for scientific queries
Name 114596 0
Guy B Marks
Address 114596 0
Woolcock Institute of Medical Research
Box M77 Missenden Road Post Office
Camperdown, NSW, 2050
Country 114596 0
Australia
Phone 114596 0
+61 419251565
Fax 114596 0
+61291140011
Email 114596 0
g.marks@unsw.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified participant data will be available for analyses
When will data be available (start and end dates)?
One year after the completion of the study with no end date.
Available to whom?
Researchers who are approved by the University of Sydney Human Research Ethics Committee after submission of a research protocol detailing the specific analyses and data required.
Available for what types of analyses?
Meta-analyses and post-hoc analyses
How or where can data be obtained?
By written request to Professor Guy Marks, g.marks@unsw.edu.au


What supporting documents are/will be available?




Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseFinding and treating both tuberculosis disease and latent infection during population-wide active case finding for tuberculosis elimination.2023https://dx.doi.org/10.3389/fmed.2023.1275140
N.B. These documents automatically identified may not have been verified by the study sponsor.