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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04528823
Recruitment Status : Recruiting
First Posted : August 27, 2020
Last Update Posted : April 26, 2022
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Dick Menzies, McGill University Health Centre/Research Institute of the McGill University Health Centre

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. 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. 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. 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.

The study population includes HIV uninfected persons aged 5-50 years who are HH contacts of individuals with newly diagnosed microbiologically confirmed active pulmonary TB. The planned number of household contacts to recruit is about 1434 in total, or about 455 for each of the three arms. The study will take place in Benin and Brazil.

The primary study outcome is, of those eligible for LTBI therapy, the proportion starting therapy within 3 months of the index TB patient starting active TB treatment. Secondary outcomes measured in each study arm include societal costs, prevalence of microbiologically confirmed and clinically diagnosed active TB, prevalence of TB infection, Incidence of adverse events, proportion who complete LTBI therapy, sensitivity and specificity of Chest Xray reading in each study side, and prevalence of active TB diagnosed using CXR in participants who cannot produce a sputum sample. Details of the statistical analysis plan for each primary and secondary outcome are provided below. Applicable for Brazil only: To evaluate the applicability and performance of material for bacteriological investigation obtained from induced sputum in children under 5 years of age.

Study participants will be recruited over 18 months. Participants will be followed until LTBI treatment is completed.


Condition or disease Intervention/treatment Phase
Latent Tuberculosis Other: Strategy 2: Symptom screen, Genexpert and TST Other: Strategy 3:Symptom screen, CXR but NO TST Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1434 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: GXT - GeneXpert or Chest-X-ray or Tuberculin Skin Testing for Household Contact Assessment: a Cluster Randomized Trial
Actual Study Start Date : January 31, 2020
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : January 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis X-Rays
Drug Information available for: X-Rays

Arm Intervention/treatment
No Intervention: Standard care (control arm)
Strategy 1: Symptoms screen, CXR and TST (standard)
Active Comparator: GeneXpert (GX)
Strategy 2: Symptoms screen, Genexpert and TST
Other: Strategy 2: Symptom screen, Genexpert and TST
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.

Active Comparator: CXR for all/NoTST
Strategy 3: Symptoms screen, CXR but NO TST
Other: Strategy 3:Symptom screen, CXR but NO TST
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.




Primary Outcome Measures :
  1. proportion starting therapy within 3 months of the index TB patient starting active TB treatment [ Time Frame: LTBI treatment initiation 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.


Secondary Outcome Measures :
  1. Societal costs (health system and patient costs) of the full cascade of care [ Time Frame: from the time of randomization until the end of investigations or the end of the second month of TB related treatment ]
    Societal costs (health system and patient costs) of the full cascade of care - from initial identification to LTBI therapy completion.

  2. Prevalence of microbiologically confirmed and clinically diagnosed active TB [ Time Frame: at baseline ]
    Prevalence of microbiologically confirmed and clinically diagnosed active TB - detected as part of the initial contact investigation, who initiate LTBI treatment within 3 months of the index TB patient starting active TB treatment.

  3. Prevalence of positive TST (>5 mm or >10 mm) [ Time Frame: at baseline ]
    Prevalence of positive TST (>5 mm or >10 mm) - overall, and by age group.

  4. Incidence of grade 1-4 adverse events related to LTBI therapy. [ Time Frame: from treatment initiation until the end of treatment case report form (CRF) has been completed ]
    Incidence of grade 1-4 adverse events related to LTBI therapy.

  5. Proportion of participants who complete LTBI therapy [ Time Frame: Approximately 4 to 6 months after treatment initiation (depending on regimen used) ]
    Completion of LTBI therapy - defined as having taken at least 80% of doses in 120% of allowed time.

  6. Sensitivity and specificity of CXR [ Time Frame: at baseline ]
    Sensitivity and specificity of CXR reading by usual providers in each study site (reference standard will be readings by external reviewers).

  7. Prevalence of active TB diagnosed using CXR in participants who cannot produce a sputum sample. [ Time Frame: at baseline ]
    Prevalence of active TB diagnosed using CXR in participants who cannot produce a sputum sample.

  8. The outcome measure of performance is the percentage of patients with valid specimens obtained by the induction of sputum over all patients with indication for this technique. [ Time Frame: at baseline ]
    Applicable for Brazil only: The outcome measure of performance is the percentage of patients with valid specimens obtained by the induction of sputum over all patients with indication for this technique.



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Ages Eligible for Study:   5 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Index TB patients:

    1. 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.

    2. Must have at least one identified household contact, and HHC investigation has not been started already.
    3. Must agree to allow research team to access their medical history and approach their household contacts.
  • Household contacts:

    1. Age 5-50 years for Benin and Age 0-50 for Brazil
    2. 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.
    3. Pregnant woman can be included.
    4. 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.

Exclusion Criteria:

  • Index TB patients:

    1. Known drug-resistant TB (INH resistant, multidrug resistance or rifampin resistance) may be excluded - after discussion in each country with TB program officials. If the TB programme's policy is to screen contacts of MDR cases for active TB only and not provide any LTBI therapy, then index TB patients with MDR will be excluded as well as their HHCs. However, if the national TB program policy is to treat such individuals with standard LTBI therapy (since some HHCs of MDR patients will develop TB with drug-sensitive isolates later), then these index TB patients and their HHCs will be eligible. Hence, this will be a country-specific exclusion criterion.
    2. 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).
    3. Only has extra-pulmonary TB.
    4. No identified household contacts.
  • Household contacts:

    1. Members of the household, but do not meet the minimum time definitions for HH contacts.
    2. Had TST/IGRA within 3 months.
    3. Had a CXR on the same day or after the date of diagnosis of the index TB patient.
    4. 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.
    5. 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04528823


Contacts
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Contact: Dick Menzies, MD 5149341934 ext 32128 dick.menzies@mcgill.ca
Contact: Chantal Valiquette 514-934-1934 ext 32577 chantal.valiquette@mail.mcgill.ca

Locations
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Benin
Centre National Hospitalier Universitaire de Pneumo Phtisiologie de Cotonou (CNHU-PPC) Recruiting
Cotonou, Benin
Contact: Menonli Adjobimey, MD    +229 66 81 45 03    menoladjobi@yahoo.fr   
Contact: Ferdinand Kassa, MD    +229 91 70 74 147    kassa_ferdinand@yahoo.fr   
Principal Investigator: Menonli Adjobimey, MD         
Brazil
Manaus Recruiting
Manaus, Brazil
Contact: Marcel Cordeiro Dos Santos       marcelocordeiro.br@gmail.com   
Principal Investigator: Marcelo Cordeiro Dos Santos         
Porto Alegre Recruiting
Porto Alegre, Brazil
Contact: Renato Stein       renatotstein@gmail.com   
Principal Investigator: Renato Stein         
Centro de Estudos, Pesquisa e Desenvolvimento Tecnológico em Saúde Coletiva - CEPESC Recruiting
Rio de Janeiro, Brazil
Contact: Anete Trajman, MD    +55 21 98218-9194    atrajman@gmail.com   
Principal Investigator: Anete Trajman, MD         
Sponsors and Collaborators
McGill University Health Centre/Research Institute of the McGill University Health Centre
Canadian Institutes of Health Research (CIHR)
Investigators
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Principal Investigator: Dick Menzies RI-MUHC
  Study Documents (Full-Text)

Documents provided by Dick Menzies, McGill University Health Centre/Research Institute of the McGill University Health Centre:
Study Protocol  [PDF] March 14, 2022
Informed Consent Form  [PDF] June 3, 2019

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Dick Menzies, Senior investigator at Research Institute of Mcgill Unniversity Health Centre, McGill University Health Centre/Research Institute of the McGill University Health Centre
ClinicalTrials.gov Identifier: NCT04528823    
Other Study ID Numbers: FND-143350-2
First Posted: August 27, 2020    Key Record Dates
Last Update Posted: April 26, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dick Menzies, McGill University Health Centre/Research Institute of the McGill University Health Centre:
Latent Tuberculosis
GeneXpert
Chest X-Ray
Tuberculin Skin Testing
Additional relevant MeSH terms:
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Tuberculosis
Latent Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
Latent Infection