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Trial registered on ANZCTR


Registration number
ACTRN12614000372684
Ethics application status
Approved
Date submitted
1/04/2014
Date registered
8/04/2014
Date last updated
23/07/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Reducing the prevalence of tuberculosis (TB) in a highly endemic setting by community-wide active case finding
Scientific title
In regions that are highly endemic for tuberculosis (TB), does community-wide active case finding, compared with routine TB control program activities, reduce the prevalence of pulmonary TB in adults and the prevalence of TB infection in children?
Secondary ID [1] 284382 0
None
Universal Trial Number (UTN)
U1111-1155-2144
Trial acronym
ACT3 (Active case finding for tuberculosis, study 3)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tuberculosis 291550 0
Condition category
Condition code
Respiratory 291932 291932 0 0
Other respiratory disorders / diseases
Infection 291933 291933 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Adult residents of intervention clusters will be screened for TB once per year for three years.
Eligible residents within each cluster will be persons aged 15 years and over who are capable of giving informed consent and who are resident in the cluster at the time of screening.
Residents will be visited in their home, informed about the study and, if they agree to be screened, will answer questions about symptoms of TB and attempt to produce a single spontaneous sputum specimen for testing. The collected sputum specimen will be tested for Mycobacterium tuberculosis using a fully automated polymerase chain reaction (PCR) (Xpert MTB/RIF, Cepheid Inc). Those who test positive will be referred to the TB treatment program for further management. We will conduct a public information campaign within the selected intervention clusters to enhance participation in the screening process. This will include meeting with community leaders, announcements broadcast over loudspeakers in the village and distributing information flyers to households.
Intervention code [1] 289110 0
Early detection / Screening
Comparator / control treatment
There will be no intervention in the control clusters. They have been informed that they will be screened in the fourth year of the study.
Control group
Active

Outcomes
Primary outcome [1] 291834 0
Prevalence of microbiologically-confirmed pulmonary tuberculosis
Timepoint [1] 291834 0
In the fourth year of the study
Primary outcome [2] 291835 0
Prevalence of tuberculosis infection in children aged six years and below
Timepoint [2] 291835 0
In the fourth year of the study
Secondary outcome [1] 307642 0
Transmission index, that is, the average number of secondary cases per index case. Secondary cases are additional cases of TB that are assumed to have arisen due to infection by the index case.
Timepoint [1] 307642 0
During the four years of the study

Eligibility
Key inclusion criteria
The primary unit of randomisation is the cluster. All clusters (sub-communes) within the Province of Ca Mau, Vietnam, are eligible for selection.
Within each cluster all persons aged 15 years and over who are capable of giving informed consent are eligible.
Minimum age
15 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Unable to give informed consent

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The unit of randomisation (cluster) is the sub-commune.

In order to ensure representativeness, selection is stratified by District. There are 9 Districts. The proportion of the adult population in each District ranges from 6.2% (Nam Can) to 17.9% (TP Ca Mau). The number of clusters to be selected in each District is calculated as this proportion multiplied by the sample size (120), rounded to the nearest 2 (to allow for random allocation to two groups within each stratum).

The primary sampling unit (PSU) is the Commune. There are 101 Communes. Communes are randomly selected with a probability proportional to size (1).

Within each District, the number of sub-communes to be selected from each Commune (PSU) is calculated based on the relative size of the Commune and the number of sub-communes to be selected for the District.

Within each Commune, the sub-communes are sorted in random order and the first n sub-communes in this list are selected. This represents the study population.

In order to ensure geographical characteristics are balanced between the randomisation groups, the allocation is stratified by District.

Next the selected sub-communes within each District are sorted by adult population size and formed into pairs, so that each pair contains sub-communes with similar adult population sizes. One member of each pair is then randomly assigned to active screening (intervention) with the other assigned to control group.

Reference
1. World Health Organization. Tuberculosis prevalence surveys: a handbook. Geneva: WHO; 2011.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The above procedure was implemented in SAS 9.3. Random numbers were generated using the RAND() function.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Cluster randomised trial.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
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 culture-proven pulmonary TB in the final year. Treatment group allocation will be the main (fixed) effect. Clusters will be treated as a random intercept term. Cluster population aged greater than or equal to 15 years will be the offset. There will be no interim analyses and a p value < 0.05 will be treated as significant. No covariates will be included in the primary analysis. Proportions will be estimated with 95% confidence intervals, adjusted for clustering.

We have made the following assumptions for the sample size calculations:
a) the average population (aged 15 years and over) per sub-commune cluster will be 1000 people;
b) the upper limit of the intra-class correlation coefficient is 0.001 (2006-07 prevalence survey).
c) the prevalence of culture-proven TB in the control clusters will be 350 per 100,000;
We will need 55 clusters (55,000 adults) in each group to have 90% power to detect a prevalence ratio for culture-proven pulmonary TB equal to 0.6 or lower (i.e., a 40% or greater reduction in prevalence). We plan to recruit 60 clusters for each study arm, to allow for drop-outs.
We estimate that for each 1000 adults aged 15 years and over, there will be 22 children aged 6 years and expect to test 15 children in each cluster, which give 90% power to detect a prevalence ratio of 0.70 or lower as different (p < 0.05).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 5953 0
Viet Nam
State/province [1] 5953 0
Ca Mau

Funding & Sponsors
Funding source category [1] 289021 0
Government body
Name [1] 289021 0
National Health and Medical Research Council (Australia)
Address [1] 289021 0
GPO Box 1421
Canberra ACT 2601
Country [1] 289021 0
Australia
Primary sponsor type
Other
Name
Woolcock Institute of Medical Research
Address
PO Box M77
Missenden Road PO
NSW 2050
Country
Australia
Secondary sponsor category [1] 287696 0
Hospital
Name [1] 287696 0
National Lung Hospital, Vietnam
Address [1] 287696 0
463 Hoang Hoa Tham, Ba Dinh, Hanoi, Vietnam.
Country [1] 287696 0
Viet Nam

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290827 0
University of Sydney Human Research Ethics Committee
Ethics committee address [1] 290827 0
University of Sydney
NSW 2006
Ethics committee country [1] 290827 0
Australia
Date submitted for ethics approval [1] 290827 0
Approval date [1] 290827 0
16/04/2013
Ethics approval number [1] 290827 0
2013/073
Ethics committee name [2] 290828 0
National Lung Hospital, Vietnam, Research Ethics Committee
Ethics committee address [2] 290828 0
463 Hoang Hoa Tham, Ba Dinh, Hanoi, Vietnam.
Ethics committee country [2] 290828 0
Viet Nam
Date submitted for ethics approval [2] 290828 0
Approval date [2] 290828 0
29/08/2013
Ethics approval number [2] 290828 0
394/2013

Summary
Brief summary
During 2010, 8.8 million people developed TB and 1.45 million people died due to the disease. In this project, which will be conducted in Vietnam, one of the countries in our region with a particularly high prevalence of TB, we will test a new form of an old intervention: community-wide screening for TB, not with x-rays but by testing sputum. If the project is successful it has the potential to lead to a giant leap forward towards the elimination of TB as a global health problem.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 47458 0
Prof Guy B. Marks
Address 47458 0
Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe 2037 NSW
Country 47458 0
Australia
Phone 47458 0
+61 419 251565
Fax 47458 0
Email 47458 0
guy.marks@sydney.edu.au
Contact person for public queries
Name 47459 0
Prof Guy B Marks
Address 47459 0
Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe 2037 NSW
Country 47459 0
Australia
Phone 47459 0
+61 2 9114 0466
Fax 47459 0
Email 47459 0
guy.marks@sydney.edu.au
Contact person for scientific queries
Name 47460 0
Prof Guy B. Marks
Address 47460 0
Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe 2037 NSW
Country 47460 0
Australia
Phone 47460 0
+61 2 9114 0466
Fax 47460 0
Email 47460 0
guy.marks@sydney.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary