Candidate Clinical Correlate of Prognostic Outcome for TB Study

Recruiting

• Conditions: Tuberculosis

• Registration Number: NCT07018076
• Lead Sponsor: University of California, San Francisco

Brief Summary

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.

Detailed Description

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 Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-04
• Study First Submitted QC: 2025-06-04
• Last Update Submitted: 2025-06-04
• Study First Posted: 2025-06-12
• Last Update Posted: 2025-06-12
• Study Start: 2025-07
• Primary Completion: 2027-07
• Study Completion: 2027-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 750

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Prognostic accuracy of novel biomarkers in predicting recurrent TB	1 year	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.
Recurrent tuberculosis (TB)	1 year	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.

Trial Locations

Locations (3)

Kisenyi Health Center; 🇺🇬 Kampala, Uganda

Mulago Outpatient Department; 🇺🇬 Kampala, Uganda

Hanoi Lung Hospital, Outpatient departments; 🇻🇳 Hanoi, Vietnam