GXT - GeneXpert or Chest-X-ray or Tuberculin Skin Testing for Household Contact Assessment

NCT04528823 | Completed DMC

• 1 other identifier: FND-143350-2
• Study Type: interventional
• Target: 1,589
• Locations: 2 countries
• Sites: 4

Brief Summary

The objective of the study is to compare outcomes from three different strategies for the management of household (HH) contacts of individuals with newly diagnosed microbiologically confirmed active pulmonary TB. The study is a cluster randomized trial with three arms of equal size. The first eligible member of the HH who provides signed informed consent to participate will be randomized to one of the three strategies. The three different study arms are as follows:

1. 1.Standard care (control arm): Participants will receive symptom screening and tuberculin skin testing (TST). If symptom screen positive and/or TST positive, they undergo chest x-rays (CXR). If CXR abnormal, they undergo microbiological investigation. If CXR normal or if microbiological investigation negative, TST positive receive latent TB infection (LTBI) treatment. If microbiological investigation is positive, they will be offered treatment for active TB. For children under 5 years of age in Brazil, sputum induction will be performed for bacteriological investigation
2. 2.GeneXpert (GX): Participants follow an algorithm similar to the standard care, however participants with positive symptom screen and/or positive TST will receive GX (i.e., GX replaces CXR in standard care algorithm). GX positive are considered to have active TB. TST positive and GX negative receive LTBI treatment. If an individual is not able to provide sputum, they will undergo a CXR.
3. 3.CXR for all/NoTST: Participants will receive symptom screening and CXR. No TST will be performed. If CXR abnormal or symptom positive, they undergo microbiological investigation. If the CXR is normal, and/or microbiological investigations negative - they receive LTBI treatment as per national guidelines. If microbiological investigation is positive they will be offered treatment for active TB.

Conditions

Latent Tuberculosis

Keywords

Latent Tuberculosis; GeneXpert; Chest X-Ray; Tuberculin Skin Testing

Outcome Measures

Primary Outcomes (1)

• proportion starting therapy within 3 months of the index TB patient starting active TB treatment

  Of those eligible (measured or estimated) for LTBI therapy, the proportion starting therapy within 3 months of the index TB patient starting active TB treatment.

  LTBI treatment initiation within 3 months of the index TB patient starting active TB treatment.

Secondary Outcomes (8)

• Societal costs (health system and patient costs) of the full cascade of care

  from the time of randomization until the end of investigations or the end of the second month of TB related treatment

• Prevalence of microbiologically confirmed and clinically diagnosed active TB

  at baseline

• Prevalence of positive TST (>5 mm or >10 mm)

  at baseline

• Incidence of grade 1-4 adverse events related to LTBI therapy.

  from treatment initiation until the end of treatment case report form (CRF) has been completed

• Proportion of participants who complete LTBI therapy

  Approximately 4 to 6 months after treatment initiation (depending on regimen used)

Study Arms (3)

Standard care (control arm)

NO INTERVENTION

Strategy 1: Symptoms screen, CXR and TST (standard)

GeneXpert (GX)

ACTIVE COMPARATOR

Strategy 2: Symptoms screen, Genexpert and TST

Other: Strategy 2: Symptom screen, Genexpert and TST

CXR for all/NoTST

ACTIVE COMPARATOR

Strategy 3: Symptoms screen, CXR but NO TST

Other: Strategy 3:Symptom screen, CXR but NO TST

Interventions

Strategy 2: Symptom screen, Genexpert and TST OTHER

Participants follow an algorithm similar to the standard care, however participants with positive symptom screen and/or positive TST will receive GX (i.e., GX replaces CXR in standard care algorithm). GX positive are considered to have active TB. TST positive and GX negative receive LTBI treatment. If an individual is not able to provide sputum, they will undergo a CXR.

GeneXpert (GX)

Strategy 3:Symptom screen, CXR but NO TST OTHER

Participants will receive symptom screening and CXR. No TST will be performed. If CXR abnormal or symptom positive, they undergo microbiological investigation. If the CXR is normal, and/or microbiological investigations negative - they receive LTBI treatment as per national guidelines. If microbiological investigation is positive they will be offered treatment for active TB.

CXR for all/NoTST

Eligibility Criteria

• Age: 5 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Index TB patients:
• New diagnosis of pulmonary microbiologically confirmed (smear, GX or culture) active TB within 30 days of treatment initiation.
• For Brazil: a new diagnosis of clinically pulmonary active is eligible.
• Must have at least one identified household contact, and HHC investigation has not been started already.
• Must agree to allow research team to access their medical history and approach their household contacts.
• Household contacts:
• Age 5-50 years for Benin and Age 0-50 for Brazil
• On average in the past 3 months - slept in the same house, at least one night per week, or spent at least one hour per day for 5 days per week.
• Pregnant woman can be included.
• People with prior active TB or latent TB therapy will be included. These participants will be assessed for prevalent active TB, although they will not be treated for LTBI. Hence they will be included in the analyses of yield of active case finding, but excluded from analyses of numbers diagnosed and treated for LTBI.

You may not qualify if:

• Index TB patients:
• Index TB patient with previous history of active TB (because their HHC may have undergone investigation before - which may change their need for study interventions, and also potentially change their perceptions and behaviours in the study).
• Only has extra-pulmonary TB.
• No identified household contacts.
• Household contacts:
• Members of the household, but do not meet the minimum time definitions for HH contacts.
• Had TST/IGRA within 3 months.
• Had a CXR on the same day or after the date of diagnosis of the index TB patient.
• People living with HIV. (In most TB programs, HH contacts have unknown HIV status; HIV testing is recommended by WHO only if the index TB patient is known to have HIV co-infection). Contacts will be asked if they have been previously diagnosed to have HIV infection, and also asked if they are taking anti-retroviral therapy (if patients are receiving any medications, these will be checked carefully to verify what these are, and in particular if they are on anti-retroviral therapy). Both questions will be asked because some patients may be on therapy, but are not aware of the indication, or they may not wish to divulge their HIV status. If HHC are on anti-retroviral therapy and/or provide a history of previous HIV diagnosis, then they will be excluded, because the WHO recommended algorithm for investigation of household contacts who are HIV infected is different from that followed in the study arms. All index TB patients should undergo HIV testing based on national algorithm. If the index TB patient is found to be HIV positive, partner notification services will be recommended to the person living with HIV. The children of women who are HIV-infected should also undergo HIV testing. HIV testing will be offered to all household contacts who have not been HIV-tested within the last 6 months. If any household contact is found to be HIV-infected, they will be excluded pre-randomization. If there is a significant delay between identification of the household contacts and obtaining the HIV result, the HHCs can be randomized and then excluded post-randomization. These HHCs will be excluded from the modified intention to treat analysis, which will be the primary analysis. All HHCs identified to have HIV-infection will undergo investigations and treatment following WHO guidelines for HIV-infected household contacts.
• If one member family refuses to participate to the study and has no objection to have the other HH members to participate in the study, then we can proceed with the consent process with the other HHC. But if one household contact refuses to participate and objects to other HH members to take part of the study, then none of the HHC in this family can participate in the study. It is not necessary that all of the HHC signed consent but simply that no one objects. At any time a participant can refuse any test, or have other investigations - as ordered by their doctor/nurse or if they prefer).

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (4)

Centre National Hospitalier Universitaire de Pneumo Phtisiologie de Cotonou (CNHU-PPC)

Cotonou, Benin

Location

Manaus

Manaus, Brazil

Location

Porto Alegre

Porto Alegre, Brazil

Location

Centro de Estudos, Pesquisa e Desenvolvimento Tecnológico em Saúde Coletiva - CEPESC

Rio de Janeiro, Brazil

Location

Related Publications (2)

• Adjobimey M, Trajman A, Bastos ML, Valiquette C, Gibson D, Djohoun F, Oxlade O, Fregonese F, Affolabi D, Kouchade V, Aguiar E, Spener-Gomes R, Cordeiro-Santos M, Stein RT, Scotta M, Benedetti A, Menzies D. Rapid molecular testing or chest X-ray or tuberculin skin testing for household contact assessment of tuberculosis infection: A cluster-randomized trial. PLoS Med. 2025 Jul 28;22(7):e1004666. doi: 10.1371/journal.pmed.1004666. eCollection 2025 Jul.

  PMID: 40720526 DERIVED

• Trajman A, Adjobimey M, Bastos ML, Valiquette C, Oxlade O, Fregonese F, Affolabi D, Cordeiro-Santos M, Stein RT, Benedetti A, Menzies D. GeneXpert or chest-X-ray or tuberculin skin testing for household contact assessment (GXT): protocol for a cluster-randomized trial. Trials. 2022 Aug 2;23(1):624. doi: 10.1186/s13063-022-06587-0.

  PMID: 35918722 DERIVED

MeSH Terms

Conditions

Latent Tuberculosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Dick Menzies

  RI-MUHC

  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: Senior investigator at Research Institute of Mcgill Unniversity Health Centre

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: August 27, 2020
• Study Start: January 31, 2020
• Primary Completion: November 30, 2022
• Study Completion: June 30, 2023
• Last Updated: July 17, 2023

Record last verified: 2023-07

Locations

BR (3); BE (1)