Enhancing the Public Health Impact of Latent Tuberculosis (TB) Infection Diagnosis and Treatment

NCT02810678 | Completed

• 1 other identifier: FND-143350
• Study Type: interventional
• Target: 24
• Locations: 5 countries
• Sites: 8

Brief 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). 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

Keywords

Tuberculosis

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  18 months

• Cross-over

  12 months

Study Arms (2)

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.

Other: Latent Tuberculosis Infection program evaluation & diagnosis

Interventions

Latent Tuberculosis Infection program evaluation & diagnosis OTHER

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Health care worker
• Only extra-pulmonary Tuberculosis
• Household contacts questionnaire
• Age ≥ 18 years old
• Informed consent signed
• 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
• Adult contact (age ≥ 18) who has already completed the child contact questionnaire
• Currently has active Tuberculosis
• Health Care worker
• Health Care worker questionnaire:
• Health care worker involved in care of Tuberculosis patients, and/or their contacts
• Age ≥ 18 years old
• Signed informed consent
• \- Has ACTIVE TUBERCULOSIS (currently or in the past)

Sponsors & Collaborators

• McGill University: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (8)

Centre de Pneumo-Phthysiologie

Cotonou, Benin

Location

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2R3, Canada

Location

University of British Columbia

Vancouver, British Columbia, V6T 1Z4, Canada

Location

Montreal Chest Institute

Montreal, Quebec, H4A 3J1, Canada

Location

Komfo Anokye Teaching Hospital (KATH)

Kumasi, Ghana

Location

University Padjadjaran (UNPAD)

Bandung, Indonesia

Location

Vietnam national university

Hanoi, Vietnam

Location

Related Publications (3)

• 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.

  PMID: 38586588 DERIVED

• Oxlade 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.

  PMID: 33765453 DERIVED

• Oxlade 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.

  PMID: 30898826 DERIVED

MeSH Terms

Conditions

Latent Tuberculosis; Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Study Officials

• Dick Menzies, MD

  Research Institute of McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Respiratory Epidemiology and Clinical Research Unit (RECRU)

Study Record Dates

• First Submitted: May 11, 2016
• First Posted: June 23, 2016
• Study Start: July 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: April 1, 2019
• Last Updated: February 21, 2020

Record last verified: 2020-02

Locations

ID (1); BE (1); GH (1); VN (1); CA (4)