Tuberculosis
Conditions
Keywords
TB
Brief summary
This substudy aims to identify cases of tuberculosis after the CoVPN 3008 clinical trial is completed.
Detailed description
This observational substudy will involve participants from the CoVPN 3008 trial, regardless of their HIV status, to study tuberculosis (TB). At the start, all participants will be screened for TB, even if they have no symptoms. They will receive chest x-rays and provide sputum samples for TB testing using Xpert Ultra, smear microscopy, and culture. The study has two main groups. Group 1 includes participants with confirmed TB, and Group 2 includes participants without TB who will act as controls. Participants with confirmed TB will start treatment and have a first follow-up visit on Day 4 to reassess TB symptoms and collect blood samples. A second follow-up visit will take place at week 26 to evaluate their treatment progress, clinical outcomes, and TB status, ensuring they receive the necessary care. Participants without TB will have a single follow-up visit on Day 4 to reassess TB symptoms and collect blood samples. The study aims to identify potential biomarkers of TB by analyzing blood samples from both cases and controls, focusing on gene expression linked to TB, including hidden (subclinical) TB.
Interventions
DIAGNOSTIC_TESTClinical Evaluation at week 26
Participants will undergo another complete physical exam and have their medical (including TB) history, potential TB signs/symptoms, and concomitant medications reassessed. Chest radiography will be obtained for all participants. An assessment of TB outcomes will also be performed.
DIAGNOSTIC_TESTClinical Evaluation at Day 4
Participants will undergo an abbreviated physical exam, assessment of concomitant medications, and reassessment for signs/symptoms of TB
DIAGNOSTIC_TESTLaboratory Evaluation at Day 4
Peripheral blood samples, including serum, PBMC, and whole blood, are collected from participants. A tongue swab is also collected from each participant.
DIAGNOSTIC_TESTLaboratory Evaluation at week 26
Peripheral blood samples, including serum, PBMC, and whole blood, will be collected. Participants not previously identified as living with HIV will undergo HIV diagnostic testing, while participants living with HIV will have their HIV viral load and CD4+ T-cell count measured.
Sponsors
COVID-19 Prevention Network
National Institute of Allergy and Infectious Diseases (NIAID)
Medical Research Council, South Africa
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Inclusion criteria
* Enrollment into the CoVPN 3008 clinical trial. * Able and willing to complete the informed consent process: Volunteer demonstrates an understanding of this substudy. * Willingness to discuss TB status, undergo related testing/monitoring labs, and receive referrals for TB care.
Exclusion criteria
* Investigator's concern for difficulty with venous access based on clinical history and physical examination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with TB | Measured at Day 1, Day 4 and week 26 | The 95% confidence interval on the proportion of participants with TB will be estimated using the "score" method |
| Association parameters of each demographic variable with confirmed TB. | Measured at Day 1, Day 4 and week 26 | Proportions and 95% CIs will be estimated using the score method. A multivariate analysis will also be conducted using generalized linear regression models with TB as the outcome. |
| Proportion of participants with confirmed TB at the six-month follow visit out of the total number of participants that are screened at the six-month visit and who had confirmed TB at their enrollment visit. | Measured at Day 1, Day 4 and week 26 | Proportion and 95% CI will be estimated using the score method. |
| Peripheral blood biomarkers associated with diagnosis of TB, including subclinical TB. | Measured at Day 1, Day 4 and week 26 | TB risk scores will be computed from RNA sequencing data generated from each participant's baseline whole-blood sample (Tempus tube) provided upon enrollment into CoVPN 3008. Association of each score with confirmed TB will be assessed using cross-validated ROC curve analysis with area under curve (AUC) 95% CI estimated using the Delong method. |
Countries
Botswana, Eswatini, Kenya, Malawi, South Africa, Uganda, Zambia
Contacts
STUDY_CHAIRNigel Garrett
eThekwini CRS / Centre for the AIDS Programme of Research in South Africa (CAPRISA)
STUDY_CHAIRPhilip Kotze
Qhakaza Mbokodo Research Clinic
STUDY_CHAIRSufia Dadabhai
Blantyre CRS / Johns Hopkins Research Project
STUDY_CHAIRNyaradzo Mgodi
University of Zimbabwe Clinical Trials Research Centre
Outcome results
None listed