Cough Audio Classification as a TB Triage Test (CAGE-TB)

April 29, 2026 updated by: Grant Theron, University of Stellenbosch

Automated Smartphone-based Cough Audio Classification for Rapid Tuberculosis Triage Testing (Cough Audio triaGE for TB; CAGE-TB)

TB is the single biggest infectious cause of death (1.5 million died in 2018), killing more HIV-positive people than any other disease, and is arguably the most important poverty-related disease in the world. TB's estimated incidence in Africa has been declining over recent years but progress is slow and plateauing. To avert stagnation, truly innovative and ambitious technologies are needed, especially those that improve case finding and time-to-diagnosis as, in mathematical models based on the TB care cascade framework, interventions that accomplish this will have the most impact on disrupting population-level transmission, including when deployed at facilities where patients are readily accessible. Critically, these interventions (triage tests) must promote access to confirmatory testing (e.g., Xpert MTB/RIF Ultra) by enabling patients to be referred rapidly and efficiently during the same visit. The investigators will optimise and evaluate a technology that, aside from the investigators early case-controlled study to show feasibility, is hitherto not meaningfully investigated for TB. This gap is alarming given, on one hand, the enormity of the TB epidemic and the need for a triage test and, on the other hand, promising proofs-of-concept that demonstrate high diagnostic accuracy of cough audio classifier for respiratory diseases such as pneumonia, asthma. pertussis, croup, and COPD. In some cases, these classification systems are CE-marked, awaiting FDA-approval, and subject to late-stage clinical trials. This demonstrates the promise of the underlying technological principle. CAGE-TB's innovation is further enhanced by: applying advanced machine learning methods that the team have specifically developed for TB patient cough audio analysis, use of mixed methods research - drawing from health economics, implementation science, and medical anthropology - to inform product design and assess barriers and facilitators to implementation, and uniquely for a TB diagnostic test, its potential deployment as a pure mHealth (smartphone-based) innovation that mitigates many barriers that typically jeopardise TPP criteria fulfilment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

CAGE-TB is a diagnostic evaluation study that assesses a TB cough audio signature's potential to be used in a smartphone application to detect potential TB from a cough sound to screen (triage) TB. The purpose of CAGE-TB is to promote the adoption of mobile health (mHealth) based cough audio triage testing for active pulmonary TB in health facilities located in high burden settings. The study is funded by the EDCTP2 programme supported by the European Union and involves four international partners. The study participants, older than 12 years, include participants who have a cough for a duration exceeding two weeks that present to healthcare clinics where the investigators have clinical recruitment infrastructure and permissions to conduct TB research. In this two-phase observational, cross-sectional study, each participant will be seen once only, at diagnosis, and no intervention is planned. In the first phase, the investigators will collect data from a discovery cohort, which will be used to train a machine learning algorithm. During the second phase, data will be collected from a validation cohort, comprising a larger number of participants from two geographically distinct study sites, which will be used to evaluate the performance of the algorithm. The aims of this study are to: (1) generate and separately validate a cough audio classifier that meets WHO triage test TPP sensitivity and specificity criteria. This aim lays the foundation for CAGE-TB by generating a classifier and a common public resource (cough sounds database) for potential later use in other studies. (2) Produce data on potential cost savings of cough audio app for triage by collecting primary data to demonstrate potential cost savings estimated using state-of-the-art methods to satisfy a key TPP criterion (<USD 2 per patient). This aim will support the further independent evaluation of the classifier, including in clinical trials focused on patient endpoints. (3) Package the technology into an easy-to-use smartphone app. Many TB tests offer improvements in accuracy and cost, but are not widely adopted. This aim is designed to mitigate this risk with the cough classifier and by using the advantages of mHealth, a product may be delivered that is readily usable by nurses, trusted by patients, and capitalised upon by healthcare providers. Accomplishing this requires incorporating important features into the mobile application, such as connectivity, automated reporting, build-in guidance, and quality control, which are important but often neglected components of the WHO triage test TPP profile. (4) Form a foundation for subsequent studies where the app will be evaluated to measure its impact on patient care, to build evidence for global policy change and adoption. The objectives of CAGE-TB include: (1.1) sampling (cough audio, sputum microbiology) all patients with a prolonged cough entering primary health facilities irrespective of reason for presentation (n=473 in Cape Town discovery cohort); (1.2) use machine learning to develop a cough audio classifier to differentiate between TB and non-TB coughs; (1.3) evaluation of the classifier for sensitivity and specificity in new validation cohorts (n=511 in Cape Town, n=767 in Kampala); (2) in both settings, the investigators will use validated tools to calculate potential provider costs averted and conduct mixed methods research to identify barriers and facilitators to inform development of the mHealth solution (smartphone app) intended for use by minimally trained health workers with the final product ideally functioning offline without necessarily needed to sync to an online server for processing done at Stichting-Amsterdam Institute for Global Health and Development (AIGHD); (3) the app will be further refined and made user-friendly, simple and visually intuitive based on study feedback towards a more final product which is free for any person to use; and (4) this mHealth solution packaged into a smartphone app will be sent for review to large international stakeholders such as the Foundation for Innovation and Diagnostics (FIND) and the World Health Organization (WHO) and lead by colleagues at AIGHD with Stellenbosch University and Makerere University input to make this TB triage application relevant for use in African settings and populations.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1751

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with a cough of at least two weeks duration self-reporting to primary care clinics in Cape Town and Kampala, in areas with a high prevalence of TB.

Description

Inclusion Criteria:

  • participant must be at least 12 years old
  • participant must have a prolonged cough (for at least two weeks)
  • participant must provide informed consent
  • participant shall have a known HIV status or be willing to undergo standard of care HIV testing and counseling

Exclusion Criteria:

  • individuals who refuse informed consent
  • individuals who have received treatment for TB in the 60 days prior to enrolment
  • individuals who are unable to provide a sputum specimen for microbiological testing
  • individuals who have haemoptysis or a bloody cough with any forced coughs for audio recordings

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Discovery Cohort
An anticipated number of 473 participants will be recruited in Cape Town, South Africa. Data (cough audio) will be collected and used to train a machine learning algorithm. The cough audio signal specific for TB will be refined. During the discovery phase, the ground truth obtained through biological testing of sputum specimens will be used to inform the machine learning.
Diagnostic test: Cough sounds
The investigators will discover a cough audio signature and then validate it.
Validation Cohort
In the validation phase, the cough audio signature will have its sensitivity and specificity measured in new patients in Cape Town, South Africa (n=511) and Kampala, Uganda (n=767). The data will be used to evaluate the performance of the algorithm.
Diagnostic test: Cough sounds
The investigators will discover a cough audio signature and then validate it.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Develop and validate algorithms that can distinguish between TB and non-TB coughs
Time Frame: 24 months
Cough audio data will be collected and used to define the cough audio signal specific for TB. The optimised TB audio signature will then have its sensitivity and specificity measured in new patients to evaluate the performance of the algorithms.
24 months
Finalised smartphone-based mHealth application
Time Frame: 30 months
The best-performing algorithm will be incorporated into a smartphone app, which will be designed with human-centered approach, that can be used as a point-of-care triage test for TB.
30 months
Avert unnecessary Ultra tests
Time Frame: 24 months
The investigators will calculate potential cost savings that the application will be able to facilitate to avoid unnecessary tests.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Stellenbosch

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Amsterdam Institute for Global Health and Development
Makerere University
University of Göttingen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Grant Theron, PhD, University of Stellenbosch

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 19, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 30, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 30, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 7, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 6, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • M21/10/022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual data will be stored and handled confidentially and anonymously. Research data will be stored under an identification code that relates to individual participants. Only the code number will be used for study documentation, annual progress reports and research publications. To trace data to an individual participant, an identification code list will be made to link the encoded data to the subject. Only the members of the research team, the site-independent monitors, members of the health care inspection, and members of the relevant Medical Ethics Committee can view research data that can be linked to individual participants. Access to the central database will be controlled via a combination of user roles and study configuration. Users are only granted privileges defined for their role in the study. The applicants will need to submit a proposal to the Trial Steering Committee for review, the applicants will also need to sign a DTA with Stellenbosch University.

IPD Sharing Time Frame

Data will be shared one year after study completion.

IPD Sharing Access Criteria

Applicants will need to submit an application to the Trial Steering Committee for data access. The Trial Steering Committee will review the application. The applicant will also need to sign a DTA with Stellenbosch University.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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