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

NCT ID: NCT02810678

Last Updated: 2020-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2019-04-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Control

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Intervention

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.

Group Type: ACTIVE_COMPARATOR

Latent Tuberculosis Infection program evaluation & diagnosis

Intervention Type: OTHER

Interventions

Latent Tuberculosis Infection program evaluation & diagnosis

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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
• 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)

Exclusion Criteria

• Health care worker
• Only extra-pulmonary Tuberculosis

2. Household contacts questionnaire

• Adult contact (age ≥ 18) who has already completed the child contact questionnaire
• Currently has active Tuberculosis
• Health Care worker

3. Health Care worker questionnaire:

• Has ACTIVE TUBERCULOSIS (currently or in the past)

4. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

McGill University

OTHER

Sponsor Role: lead

Responsible Party

Dr. Dick Menzies

Director of Respiratory Epidemiology and Clinical Research Unit (RECRU)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dick Menzies, MD

Role: PRINCIPAL_INVESTIGATOR

Research Institute of McGill University Health Centre

Locations

Centre de Pneumo-Phthysiologie

Cotonou, , Benin

University of Calgary

Calgary, Alberta, Canada

University of Alberta

Edmonton, Alberta, Canada

University of British Columbia

Vancouver, British Columbia, Canada

Montreal Chest Institute

Montreal, Quebec, Canada

Komfo Anokye Teaching Hospital (KATH)

Kumasi, , Ghana

University Padjadjaran (UNPAD)

Bandung, , Indonesia

Vietnam national university

Hanoi, , Vietnam

Countries

Benin; Canada; Ghana; Indonesia; Vietnam

References

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.

Reference Type: DERIVED

PMID: 38586588 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33765453 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30898826 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

FND-143350

Identifier Type: -

Identifier Source: org_study_id