Early Risk Assessment in Household Contacts (≥10 Years) of TB Patients by New Diagnostic Tests in 3 African Countries
NCT ID: NCT04781257
Last Updated: 2023-11-28
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
ACTIVE_NOT_RECRUITING
2100 participants
OBSERVATIONAL
2021-03-01
2024-04-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
These people would benefit from preventive treatment, which would also stop TB from being spread to other persons.
The problem currently is that it is impossible to determine with certainty who would require preventive treatment, and who will remain healthy. Out of 100 persons exposed to an infectious TB patient, only 2 will go on to have TB according to a study in Vietnam, but there are no good tests available to identify those with a risk for TB disease. Treating 100 persons to prevent 2 cases of TB is not effective, so preventive treatment is not used in adults and adolescents in Tanzania, Mozambique and Zimbabwe, where this study will be conducted, but also in many other settings.
The ERASE - TB project will evaluate a number of newly developed diagnostic tests, to see which of those will be able to predict TB in persons at risk, and therefore steer preventive treatment well.
For this, the investigators will invite 2,100 household contacts (HHC) of infectious TB patients, who are at least 10 years old, into the study. Everyone will be examined initially, and again in regular intervals, for 1.5 to 2 years; and whenever the participants will present with symptoms that could indicate that they develop TB.
At every visit, the investigators will perform an X-ray and take some blood and urine samples to perform new candidate tests. At the first/baseline visit, all household contacts without TB will undergo a spirometry to evaluate their pulmonary function.
If someone is unwell, the investigators will also examine sputum for the presence of TB bacilli. In the end, the investigators will then be able to say who of the persons in the study developed TB, and who remained healthy. From all samples taken at different timepoints, the investigators will then determine which test found TB early, and clearly distinguished between persons developing TB, and persons who would remain healthy .
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
COHORT
PROSPECTIVE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Household contacts with co-prevalent/incipient TB
Household contacts diagnosed with active TB at baseline/during the study period
New test candidates
The following new diagnostic tests will be done after the completion of the study with the samples (blood, sputum, urine) and data (digital X-ray) obtained during the study period:
CAD4TB / qXR Xpert Ultra® FLOW-TB TAM-TB 4RISK and COR Cepheid 3-gene signature cartridge BioMérieux ISIT TB blood transcription signature assay Multiplex LSHTM in-house host biomarker assay TB Screen biosignature SeroSelect
Retrospective testing of participants' samples and data acquired during the study period, differentiated between participants with co-prevalent/incipient TB and participants staying health throughout the trial
Household contacts staying healthy
Household contacts without active TB who remain healthy throughout the study
New test candidates
The following new diagnostic tests will be done after the completion of the study with the samples (blood, sputum, urine) and data (digital X-ray) obtained during the study period:
CAD4TB / qXR Xpert Ultra® FLOW-TB TAM-TB 4RISK and COR Cepheid 3-gene signature cartridge BioMérieux ISIT TB blood transcription signature assay Multiplex LSHTM in-house host biomarker assay TB Screen biosignature SeroSelect
Retrospective testing of participants' samples and data acquired during the study period, differentiated between participants with co-prevalent/incipient TB and participants staying health throughout the trial
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
New test candidates
The following new diagnostic tests will be done after the completion of the study with the samples (blood, sputum, urine) and data (digital X-ray) obtained during the study period:
CAD4TB / qXR Xpert Ultra® FLOW-TB TAM-TB 4RISK and COR Cepheid 3-gene signature cartridge BioMérieux ISIT TB blood transcription signature assay Multiplex LSHTM in-house host biomarker assay TB Screen biosignature SeroSelect
Retrospective testing of participants' samples and data acquired during the study period, differentiated between participants with co-prevalent/incipient TB and participants staying health throughout the trial
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Aged at least 18 years
* Having at least one other person living in the household aged ≥10 years
* Written informed consent to conduct socio-economic and clinical questionnaire, to provide a sputum sample for culture and sequencing, and to approach the household members.
* Recently diagnosed with active pulmonary TB within the last 4 weeks
* Has taken less than 7 daily doses of anti-TB treatment since diagnosis; ensuring a positive culture can still be obtained
* Able to spontaneously produce sputum
* Sputum microscopy positive in Ziehl-Neelsen or Auramine-O staining of ideally 2+ or higher, but at least 1+ on the IUATLD/WHO scale, OR (in case no sputum microscopy done) GeneXpert positive, at least TB "medium"
* A firm home address, maintained unchanged for the last 6 months, that is accessible to visiting
Household Contact:
* Aged at least 10 years
* Written informed consent for study participation, including HIV testing, and home visits by the study team for follow-up (for minors \<18 yr.: consent of the parent/guardian, assent of the participant)
* Recent (in the last 4 weeks), substantial exposure to an infectious TB case in the household, defined as sleeping at least 3/7 nights in the same household
* If HIV negative: not on preventive therapy (preventive therapy is not an exclusion criterion for HIV positive persons)
Exclusion Criteria
* Circumstances that raise doubt on free, uncoerced informed consent (e.g. in a mentally handicapped person)
* Prisoners
* Recent treatment for active TB, completed within the last 30 days OR on current TB treatment for active TB.
10 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
European and Developing Countries Clinical Trials Partnership (EDCTP)
OTHER_GOV
Michael Hoelscher
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Michael Hoelscher
Professor Dr.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Theodora Mbunda, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
National Institute of Medical Research - Mbeya Medical Research Centre
Denise F Banze, MD
Role: PRINCIPAL_INVESTIGATOR
Instituto Nacional de Saúde (INS)
Junior Mutsvangwa, MD
Role: PRINCIPAL_INVESTIGATOR
Biomedical Research & Training Institute (BRTI)
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Instituto Nacional de Saúde (INS) Centro de Investigação e Treino em Saúde da Polana Caniço
Maputo, , Mozambique
NIMR - Mbeya Medical Research Centre
Mbeya, , Tanzania
Biomedical Research & Training Institute (BRTI)
Harare, , Zimbabwe
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Drain PK, Bajema KL, Dowdy D, Dheda K, Naidoo K, Schumacher SG, Ma S, Meermeier E, Lewinsohn DM, Sherman DR. Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection. Clin Microbiol Rev. 2018 Jul 18;31(4):e00021-18. doi: 10.1128/CMR.00021-18. Print 2018 Oct.
Fox GJ, Nhung NV, Sy DN, Hoa NLP, Anh LTN, Anh NT, Hoa NB, Dung NH, Buu TN, Loi NT, Nhung LT, Hung NV, Lieu PT, Cuong NK, Cuong PD, Bestrashniy J, Britton WJ, Marks GB. Household-Contact Investigation for Detection of Tuberculosis in Vietnam. N Engl J Med. 2018 Jan 18;378(3):221-229. doi: 10.1056/NEJMoa1700209.
Swindells S, Ramchandani R, Gupta A, Benson CA, Leon-Cruz J, Mwelase N, Jean Juste MA, Lama JR, Valencia J, Omoz-Oarhe A, Supparatpinyo K, Masheto G, Mohapi L, da Silva Escada RO, Mawlana S, Banda P, Severe P, Hakim J, Kanyama C, Langat D, Moran L, Andersen J, Fletcher CV, Nuermberger E, Chaisson RE; BRIEF TB/A5279 Study Team. One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis. N Engl J Med. 2019 Mar 14;380(11):1001-1011. doi: 10.1056/NEJMoa1806808.
Marambire ET, Banze D, Mfinanga A, Mutsvangwa J, Mbunda TD, Ntinginya NE, Celso K, Kallenius G, Calderwood CJ, Geldmacher C, Held K, Appalarowthu T, Riess F, Panzner U, Heinrich N, Kranzer K; ERASE-TB Consortium. Early risk assessment in paediatric and adult household contacts of confirmed tuberculosis cases by novel diagnostic tests (ERASE-TB): protocol for a prospective, non-interventional, longitudinal, multicountry cohort study. BMJ Open. 2022 Jul 19;12(7):e060985. doi: 10.1136/bmjopen-2022-060985.
Related Links
Access external resources that provide additional context or updates about the study.
WHO Global Tuberculosis Report 2019
Consensus Meeting Report: Development of a Target Product Profile (TPP) and a framework for evaluation for a test for predicting progression from tuberculosis infection to active disease
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
LMU-IMPH-AIDA-03
Identifier Type: -
Identifier Source: org_study_id