Clinical trial NCT02810678: Enhancing the Public Health Impact of Latent Tuberculosis (TB) Infection Diagnosis and Treatment
Official title: Enhancing the Public Health Impact of Latent Tuberculosis (TB) Infection Diagnosis and Treatment: A Pragmatic Cluster Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Latent Tuberculosis Infection
Keywords: Tuberculosis
Lead sponsor: McGill University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2016-06-23
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: Details vary depending on the study tool/measurement being taken. For Phase 1 questionniares (in 4 different populations) criteria are as follows:

1. Index case questionnaire:

   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

   Exclusion Criteria:
   * Health care worker
   * Only extra-pulmonary Tuberculosis
2. Household contacts questionnaire

   Inclusion Criteria:
   * 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

   Exclusion criteria:
   * Adult contact (age ≥ 18) who has already completed the child contact questionnaire
   * Currently has active Tuberculosis
   * Health Care worker
3. Health Care worker questionnaire:

   Inclusion criteria:
   * Health care worker involved in care of Tuberculosis patients, and/or their contacts
   * Age ≥ 18 years old
   * Signed informed consent

   Exclusion criteria:

   - Has ACTIVE TUBERCULOSIS (currently or in the past)
4. Parents of Children (under 5 years of age) who were Household contact

Inclusion criteria:

* 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:

* 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

Primary outcomes:
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
timeFrame: 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:
measure: Health system costs related to the implementation of the LTBI program evaluation and strengthening approach
timeFrame: 18 months
measure: Cross-over
timeFrame: 12 months
Other outcomes:
Locations:
city: Cotonou
country: Benin
facility: Centre de Pneumo-Phthysiologie
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Montreal
country: Canada
facility: Montreal Chest Institute
state: Quebec
city: Kumasi
country: Ghana
facility: Komfo Anokye Teaching Hospital (KATH)
city: Bandung
country: Indonesia
facility: University Padjadjaran (UNPAD)
city: Hanoi
country: Vietnam
facility: Vietnam national university
Study officials:
affiliation: Research Institute of McGill University Health Centre
name: Dick Menzies, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.