Candidate Clinical Correlate of Prognostic Outcome for TB Study

University of California, San Francisco750 enrolled

Overview

As part of the ongoing efforts within the Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) study, the Candidate Clinical Correlate as Prognostic Outcome for TB (C3PO) study serves as a supplement aimed at evaluating predictors and novel biomarkers of recurrent TB among TB survivors. Current tools for predicting TB recurrence risk are suboptimal, limiting the ability to assess new TB treatment regimens effectively. Identifying accurate sputum- or blood-based biomarkers for recurrence risk could significantly improve the efficiency and informativeness of Phase 2 and 3 clinical trials.

The Candidate Clinical Correlate as Prognostic Outcome for TB Study (C3PO) supplements the ongoing Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) study by identifying and accelerating novel TB diagnostics at various stages of development and across different use cases. There is an urgent need for treatments that can cure all forms of TB more quickly. However, the development of new, shorter, and more effective antibiotic regimens is hindered by the limitations of current methods used to assess treatment effectiveness in TB drug trials. The standard pharmacodynamic (PD) marker-sputum culture-does not predict clinical outcomes well, fails to detect residual Mycobacterium tuberculosis that causes relapse, and takes 6-8 weeks to provide results. New PD markers that more accurately predict clinical outcomes would help de-risk clinical trials and ensure that only the most effective new regimens move forward. C3PO aims to evaluate non-culture PD markers in predicting recurrent TB among patients who have completed the global standard HRZE regimen for drug-susceptible pulmonary TB under routine programmatic settings.

Study Type

OBSERVATIONAL

Enrollment

750

Conditions

Tuberculosis

Interventions

RS ratioDIAGNOSTIC_TEST

We will evaluate the non-culture, sputum-based assay RS ratio, which measures ongoing Mycobacterium tuberculosis activity by quantifying the abundance of precursor rRNA relative to mature rRNA (an indicator of active rRNA synthesis).

Blood-based host immune response assaysDIAGNOSTIC_TEST

We will evaluate blood-based assays measuring host immune response parameters for predicting mycobacterial activity.

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. . individuals age ≥ 12 years; 2. . have completed treatment for drug-susceptible tuberculosis with the standard 6-month regimen of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE). Exclusion Criteria: 1. completed treatment for drug-susceptible tuberculosis \>14 days prior to screening/enrollment; 2. routinely taking any medication with anti-mycobacterial activity (including fluoroquinolones) for any reason not related to tuberculosis treatment within the last 14 days; 3. unwilling to provide informed consent or return for study follow-up visits.

Locations (3)

Kisenyi Health Center

Kampala, Uganda

RECRUITING

Mulago Outpatient Department

Kampala, Uganda

RECRUITING

Hanoi Lung Hospital, Outpatient departments

Hanoi, Vietnam

NOT_YET_RECRUITING

Outcomes

Primary Outcomes

Recurrent tuberculosis (TB)

Recurrent tuberculosis (TB), defined as a new episode of microbiologically confirmed TB occurring after completion of treatment for a prior drug-sensitive TB episode. Recurrence will be identified through routine study visits during the one year follow-up, with microbiological confirmation based on sputum mycobacterial culture.

Time frame: 1 year

Prognostic accuracy of novel biomarkers in predicting recurrent TB

We will evaluate the ability of selected novel biomarkers to predict recurrent TB using the following metrics: Area Under the Curve (AUC): Measures the overall discriminatory ability of the biomarkers to distinguish between individuals who will and will not experience recurrent TB. Sensitivity and Specificity: Sensitivity indicates how accurately the biomarkers identify individuals who will develop recurrent TB, while specificity reflects how well they identify those who will not. Positive Predictive Value (PPV) and Negative Predictive Value (NPV): PPV represents the proportion of individuals with a positive biomarker result who actually develop recurrent TB, while NPV reflects the proportion with a negative result who remain recurrence-free. Kappa Statistic: Assesses the agreement between predicted outcomes based on the biomarkers and the actual observed outcomes, accounting for agreement occurring by chance.