Latent Tuberculosis InfectionACT4NCT02810678
Enhancing the Public Health Impact of Latent Tuberculosis (TB) Infection Diagnosis and Treatment
A study testing Latent Tuberculosis Infection program evaluation & diagnosis in people with Latent Tuberculosis Infection, run by McGill University at 8 sites in 5 countries.
Trial summary
The study is a pragmatic cluster randomized trial that is being conducted in 5 countries, with sites in 4 cities in Canada, Benin, Ghana, Indonesia and Vietnam. The unit of randomization is the health facility (24 health facilities randomized). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Latent Tuberculosis Infection
- What is being tested?
- Latent Tuberculosis Infection program evaluation & diagnosis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 8 sitesin 5 countries
- Study dates
- Jul 2016to Apr 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed patients with microbiologically confirmed active pulmonary Tuberculosis (Pulmonary Tuberculosis - smear or culture or GeneXpert positive or Nucleic Acid Amplification test (NAAT)
- Age ≥ 18 years old
- At least 1 Household contact, with contact investigation underway
- Signed informed consent
- Age ≥ 18 years old
- Informed consent signed
Show all 17Show fewer
- Sleeps in the same house at least 1 night per week during the past 3 months with person who has confirmed active Tuberculosis OR
- Spent more than one hour per day in the house for at least 5 days per week with person who has active Tuberculosis - in the past 3 months
- Health care worker involved in care of Tuberculosis patients, and/or their contacts
- Age ≥ 18 years old
- Signed informed consent
- Age ≥ 18 years old
- Signed informed consent
- Parent/legal guardian/responsible caregiver of child under 5 years of age
- And one of the following two mandatory eligibility criteria:
- Child sleeps in the same house at least 1 night per week during the past 3 months with person who has active pulmonary Tuberculosis OR
- Child spent more than one hour per day in the house for at least 5 days per week with person who has active pulmonary Tuberculosis ( in the past 3 months)
Who cannot join
- Health care worker
- Only extra-pulmonary Tuberculosis
- Household contacts questionnaire
- Adult contact (age ≥ 18) who has already completed the child contact questionnaire
- Currently has active Tuberculosis
- Health Care worker
Show all 12Show fewer
- Health Care worker questionnaire:
- Has ACTIVE TUBERCULOSIS (currently or in the past)
- Parents of Children (under 5 years of age) who were Household contact
- The parent is the source (Index) case
- The parents is an Aadult contact who has already completed the contact questionnaire for adults
- The child currently has active Tuberculosis
Trial locations and contacts
8 sites in 5 countries.
8 sites in 5 countries
Canada4 sites
University of Calgary
Calgary, Alberta, T2N 1N4
University of Alberta
Edmonton, Alberta, T6G 2R3
Montreal Chest Institute
Montreal, Quebec, H4A 3J1
University of British Columbia
Vancouver, British Columbia, V6T 1Z4
About this study
Official title: Enhancing the Public Health Impact of Latent Tuberculosis (TB) Infection Diagnosis and Treatment: A Pragmatic Cluster Randomized Trial
The study is a pragmatic cluster randomized trial that is being conducted in 5 countries, with sites in 4 cities in Canada, Benin, Ghana, Indonesia and Vietnam. The unit of randomization is the health facility (24 health facilities randomized). The trial tests a complex intervention-a two phase programmatic public health package which includes a standardized public health evaluation and analysis, to identify problems and barriers limiting Latent Tuberculosis Infection diagnosis and treatment among close contacts of active Tuberculosis cases. This will be followed by implementation of appropriate solutions and strengthening of the LTBI clinical program. The primary objective will be to estimate the increase the number of household contacts initiating LTBI treatment per newly diagnosed index patient, within 3 months of diagnosis of the index patient. A secondary objective is to evaluate the cost effectiveness of this two phase intervention. If successful, this approach can be expanded throughout these countries. After initial preparations, including administrative and ethical review, all participating sites will be randomized to intervention or control. Immediately after this, Phase 1 will begin in intervention sites with the standardized public health evaluation to identify barriers to LTBI diagnosis and treatment initiation and the selection of solutions to be used in Phase 2. To ensure standardization of data gathering research staff will use (i) current indicators of the Latent Tuberculosis Infection cascade of care in intervention facilities (number of contacts per index case registered, investigated, started on treatment and completing treatment) and (ii) interviewer administered questionnaires for patients with active pulmonary Tuberculosis, adult and child household contacts and clinic staff. These questionnaires will assess latent Tuberculosis-related knowledge, attitudes and beliefs from the perspective of these different participants. Results from intervention sites in Phase 1 will be analyzed, and used by the investigators, together with local public health officials, to decide on appropriate corrective solutions in each sites. Contact Investigation registries will also be developed with research staff from sites. In Phase 2, solutions for problems identified will be selected and implemented at the intervention sites, Contact Investigation registries will be implemented and clinical training will be provided to strengthen LTBI health care worker knowledge and clinical programs. Study outcomes and costs will be measured at all intervention and control sites throughout Phase 1 \& 2. The main study will run for 18 months. Upon completion of the main study, a 1 year cross over study will be conducted where control sites will receive a streamlined version of the intervention and original intervention sites will be used to evaluate the sustainability of the intervention. Results will be disseminated within each country through existing links with National Tuberculosis Programs, and through international organizations such as the World Health Organization.
- Conditions
- Latent Tuberculosis Infection
- Being tested
- Latent Tuberculosis Infection program evaluation & diagnosis
- Keywords
- Tuberculosis
- Medical subject headings
- Latent Tuberculosis, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Latent Tuberculosis Infection program evaluation & diagnosisOther
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | No Intervention: Program runs as per usual. Minimal interference and visits from study staff. Main study outcomes evaluated in first and last 6 months of trial. Minimal visits to collect information on costing at control sites. |
| Intervention | Active comparator | Latent Tuberculosis Infection program evaluation \& diagnosis: In intervention health facilities the current Latent Tuberculosis Infection program will be evaluated and gaps in the Latent Tuberculosis Infection cascade of care will be identified. Gaps in the current cascade will be quantified and solution proposed that are unique to the problems identified in each site. In phase 2 of the study low cost solutions will be implemented and the Latent Tuberculosis Infection program scaled up and improved. Study outcomes are evaluated in the first and last 6 months of trial. Costing evaluations are done throughout the trial. Receives: Other: Latent Tuberculosis Infection program evaluation & diagnosis |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome will be the change in the number of household contacts (HHC) initiating treatment per newly diagnosed TB index patient within 3- 4 months from index patient diagnosis, between Phase 1 and Phase 2
A new TB index patient will be microbiologically confirmed using AFB smear, culture, and/or molecular tests such as Xpert®MTB/RIF, depending on local protocols. A HHC will be defined as someone who slept in the same house at least one night per week, or spent more than one hour in the house at least five days per week, on average, over the preceding 3 months. The house will be defined as the dwelling, or buildings, which the family unit occupies and uses regularly. In each of the 6 month periods, the total number of index patients, the number of their contacts who were recorded in clinic documents, and the number of these HHC who initiate LTBI therapy will be collected in both the control and intervention arms. For TB index patients diagnosed towards the end of each 6-month period in most sites we will allow up to 3 or 4 additional months for the HHC to be started on LTBI treatment.
Measured: The primary outcome will be recorded at all health facilities for the full duration of phase 1 (6 months) and for the last 6 months of phase 2.
Secondary outcomes (2)
Health system costs related to the implementation of the LTBI program evaluation and strengthening approach
Throughout the trial, costs related to the implementation of the LTBI program evaluation and strengthening will be measured in each setting, using time and activity logs for research staff, investigators, health care workers and management staff involved in implementation. Country specific budgets will be used to obtain expenditures related to services, supplies and materials. To estimate LTBI related health system personnel costs, time and motion studies will be conducted at the start of phase 1 and the end of phase 2.
Measured: 18 months
Cross-over
To evaluate the sustained effect of this complex intervention for one year after the end of the randomized trial - at original intervention sites.To evaluate the costs, and impact of a stream-lined Phase 1 and 2 - administered to control sites, after the 18 month trial.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2016 (estimated)
- Study startJul 2016
- Primary completionDec 2018
- Study completionApr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Latent Tuberculosis InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- McGill University
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Principal investigator, Dr. Dick Menzies, McGill University
- Investigators
- Dick Menzies, MD, Principal investigator, Research Institute of McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02810678
- Sponsor's protocol ID
- FND-143350
- Acronym
- ACT4
- Status last verified
- Feb 2020
- First submitted
- 11 May 2016
- Last updated
- 21 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Menzies D, Obeng J, Hadisoemarto P, Ruslami R, Adjobimey M, Fisher D, Barss L, Bedingfield N, Long R, Paulsen C, Johnston J, Romanowski K, Cook VJ, Fox GJ, Nguyen TA, Valiquette C, Oxlade O, Fregonese F, Benedetti A. Sustainability and impact of an intervention to improve initiation of tuberculosis preventive treatment: results from a follow-up study of the ACT4 randomized trial. EClinicalMedicine. 2024 Mar 28;71:102546. doi: 10.1016/j.eclinm.2024.102546. eCollection 2024 May.
PubMed 38586588Oxlade O, Benedetti A, Adjobimey M, Alsdurf H, Anagonou S, Cook VJ, Fisher D, Fox GJ, Fregonese F, Hadisoemarto P, Hill PC, Johnston J, Khan FA, Long R, Nguyen NV, Nguyen TA, Obeng J, Ruslami R, Schwartzman K, Trajman A, Valiquette C, Menzies D. Effectiveness and cost-effectiveness of a health systems intervention for latent tuberculosis infection management (ACT4): a cluster-randomised trial. Lancet Public Health. 2021 May;6(5):e272-e282. doi: 10.1016/S2468-2667(20)30261-9. Epub 2021 Mar 22.
PubMed 33765453Oxlade O, Trajman A, Benedetti A, Adjobimey M, Cook VJ, Fisher D, Fox GJ, Fregonese F, Hadisoemarto P, Hill PC, Johnston J, Long R, Obeng J, Ruslami R, Valiquette C, Menzies D. Enhancing the public health impact of latent tuberculosis infection diagnosis and treatment (ACT4): protocol for a cluster randomised trial. BMJ Open. 2019 Mar 20;9(3):e025831. doi: 10.1136/bmjopen-2018-025831.
PubMed 30898826
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhancing the Public Health Impact of Latent Tuberculosis (TB) Infection Diagnosis and Treatment: A Pragmatic Cluster Randomized Trial
- ClinicalTrials.gov ID
- NCT02810678
- Acronym / sponsor ID
- ACT4 / FND-143350
- Conditions
- Latent Tuberculosis Infection
- Keywords
- Tuberculosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- McGill UniversityUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- Jul 2016 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Apr 2019 (actual)
- First posted
- 23 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is a pragmatic cluster randomized trial that is being conducted in 5 countries, with sites in 4 cities in Canada, Benin, Ghana, Indonesia and Vietnam. The unit of randomization is the health facility (24 health facilities randomized). The trial tests a complex intervention-a two phase programmatic public health package which includes a standardized public health evaluation and analysis, to identify problems and barriers limiting Latent Tuberculosis Infection diagnosis and treatment among close contacts of active Tuberculosis cases. This will be followed by implementation of appropriate solutions and strengthening of the LTBI clinical program. The primary objective will be to estimate the increase the number of household contacts initiating LTBI treatment per newly diagnosed index patient, within 3 months of diagnosis of the index patient. A secondary objective is to evaluate the cost effectiveness of this two phase intervention. If successful, this approach can be expanded throughout these countries. After initial preparations, including administrative and ethical review, all participating sites will be randomized to intervention or control. Immediately after this, Phase 1 will begin in intervention sites with the standardized public health evaluation to identify barriers to LTBI diagnosis and treatment initiation and the selection of solutions to be used in Phase 2. To ensure standardization of data gathering research staff will use (i) current indicators of the Latent Tuberculosis Infection cascade of care in intervention facilities (number of contacts per index case registered, investigated, started on treatment and completing treatment) and (ii) interviewer administered questionnaires for patients with active pulmonary Tuberculosis, adult and child household contacts and clinic staff. These questionnaires will assess latent Tuberculosis-related knowledge, attitudes and beliefs from the perspective of these different participants. Results from intervention sites in Phase 1 will be analyzed, and used by the investigators, together with local public health officials, to decide on appropriate corrective solutions in each sites. Contact Investigation registries will also be developed with research staff from sites. In Phase 2, solutions for problems identified will be selected and implemented at the intervention sites, Contact Investigation registries will be implemented and clinical training will be provided to strengthen LTBI health care worker knowledge and clinical programs. Study outcomes and costs will be measured at all intervention and control sites throughout Phase 1 \& 2. The main study will run for 18 months. Upon completion of the main study, a 1 year cross over study will be conducted where control sites will receive a streamlined version of the intervention and original intervention sites will be used to evaluate the sustainability of the intervention. Results will be disseminated within each country through existing links with National Tuberculosis Programs, and through international organizations such as the World Health Organization.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –No Intervention: Program runs as per usual. Minimal interference and visits from study staff. Main study outcomes evaluated in first and last 6 months of trial. Minimal visits to collect information on costing at control sites. |
| Intervention | Active comparator | Other: Latent Tuberculosis Infection program evaluation & diagnosisLatent Tuberculosis Infection program evaluation \& diagnosis: In intervention health facilities the current Latent Tuberculosis Infection program will be evaluated and gaps in the Latent Tuberculosis Infection cascade of care will be identified. Gaps in the current cascade will be quantified and solution proposed that are unique to the problems identified in each site. In phase 2 of the study low cost solutions will be implemented and the Latent Tuberculosis Infection program scaled up and improved. Study outcomes are evaluated in the first and last 6 months of trial. Costing evaluations are done throughout the trial. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Age ≥ 18 years old
- Signed informed consent
- Parent/legal guardian/responsible caregiver of child under 5 years of age
- Child sleeps in the same house at least 1 night per week during the past 3 months with person who has active pulmonary Tuberculosis OR
- Child spent more than one hour per day in the house for at least 5 days per week with person who has active pulmonary Tuberculosis ( in the past 3 months)
Key exclusion criteria (12 listed)
- Household contacts questionnaire
- Health Care worker questionnaire:
- Parents of Children (under 5 years of age) who were Household contact
- The parent is the source (Index) case
- The parents is an Aadult contact who has already completed the contact questionnaire for adults
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Latent Tuberculosis Infection program evaluation & diagnosis | Other | Intervention |
Primary outcome
The primary outcome will be the change in the number of household contacts (HHC) initiating treatment per newly diagnosed TB index patient within 3- 4 months from index patient diagnosis, between Phase 1 and Phase 2
Time frame: The primary outcome will be recorded at all health facilities for the full duration of phase 1 (6 months) and for the last 6 months of phase 2.
A new TB index patient will be microbiologically confirmed using AFB smear, culture, and/or molecular tests such as Xpert®MTB/RIF, depending on local protocols. A HHC will be defined as someone who slept in the same house at least one night per week, or spent more than one hour in the house at least five days per week, on average, over the preceding 3 months. The house will be defined as the dwelling, or buildings, which the family unit occupies and uses regularly. In each of the 6 month periods, the total number of index patients, the number of their contacts who were recorded in clinic documents, and the number of these HHC who initiate LTBI therapy will be collected in both the control and intervention arms. For TB index patients diagnosed towards the end of each 6-month period in most sites we will allow up to 3 or 4 additional months for the HHC to be started on LTBI treatment.
2 secondary outcomes
Health system costs related to the implementation of the LTBI program evaluation and strengthening approach
Time frame: 18 months
Cross-over
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2020.
- Derived from this study: PubMed 38586588Menzies D, Obeng J, Hadisoemarto P, Ruslami R, Adjobimey M, Fisher D, Barss L, Bedingfield N, Long R, Paulsen C, Johnston J, Romanowski K, Cook VJ, Fox GJ, Nguyen TA, Valiquette C, Oxlade O, Fregonese F, Benedetti A. Sustainability and impact of an intervention to improve initiation of tuberculosis preventive treatment: results from a follow-up study of the ACT4 randomized trial. EClinicalMedicine. 2024 Mar 28;71:102546. doi: 10.1016/j.eclinm.2024.102546. eCollection 2024 May.
- Derived from this study: PubMed 33765453Oxlade O, Benedetti A, Adjobimey M, Alsdurf H, Anagonou S, Cook VJ, Fisher D, Fox GJ, Fregonese F, Hadisoemarto P, Hill PC, Johnston J, Khan FA, Long R, Nguyen NV, Nguyen TA, Obeng J, Ruslami R, Schwartzman K, Trajman A, Valiquette C, Menzies D. Effectiveness and cost-effectiveness of a health systems intervention for latent tuberculosis infection management (ACT4): a cluster-randomised trial. Lancet Public Health. 2021 May;6(5):e272-e282. doi: 10.1016/S2468-2667(20)30261-9. Epub 2021 Mar 22.
- Derived from this study: PubMed 30898826Oxlade O, Trajman A, Benedetti A, Adjobimey M, Cook VJ, Fisher D, Fox GJ, Fregonese F, Hadisoemarto P, Hill PC, Johnston J, Long R, Obeng J, Ruslami R, Valiquette C, Menzies D. Enhancing the public health impact of latent tuberculosis infection diagnosis and treatment (ACT4): protocol for a cluster randomised trial. BMJ Open. 2019 Mar 20;9(3):e025831. doi: 10.1136/bmjopen-2018-025831.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dick Menzies, MD principal investigator
Research Institute of McGill University Health Centre
8 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Latent Tuberculosis Infection program evaluation & diagnosis in people with Latent Tuberculosis Infection, run by McGill University at 8 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Canada, Benin, Ghana, Indonesia, Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome will be the change in the number of household contacts (HHC) initiating treatment per newly diagnosed TB index patient within 3- 4 months from index patient diagnosis, between Phase 1 and Phase 2 (time frame: The primary outcome will be recorded at all health facilities for the full duration of phase 1 (6 months) and for the last 6 months of phase 2.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02810678, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2020.