TuberculosisRaPaedNCT03734172
Rapid and Accurate Diagnosis of Paediatric TB (RaPaed-AIDA-TB)
An observational study of Tuberculosis and Diagnoses Disease, run by Michael Hoelscher at 5 sites in 5 countries.
Trial summary
This study will serve as a platform to evaluate new diagnostics in children suspected to have TB, establish diagnostic performance (sensitivity and specificity) and calculate positive and negative predictive values in a real-life cohort. Finally, this study will comprise the results of several tests in its database. Read more about this study
- Who is it for?
- Ages Up to 14 years
- Conditions the study is for
- Tuberculosis, Diagnoses Disease
- What is being tested?
- Sample collection
- How many people
- 974 participants
- Where
- 5 sitesin 5 countries
- Study dates
- 21 Jan 2019to 31 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 14 years
- All sexes
- No healthy volunteers
- Child
Study population: Patients 14 years old or younger with a suspicion of active TB are eligible for recruitment into the study, if they meet the specified inclusion criteria, and none of the exclusion criteria.
Who may be able to join
- Consent and Assent (if applicable): signed written consent/assent, or witnessed oral consent/assent in the case of illiteracy, before undertaking any study-specific activity. The age threshold for child assent requirement will be laid down in each the Investigator Site File based on the local Ethics Committee requirement.
- Of the following, either criterion 2), OR criterion 3), or both, have to be met:
- Confirmation of TB disease: microbiological confirmation of active TB disease by positive smear AND/OR culture AND/OR PCR (e.g. GeneXpert®); e.g. in a non-study health facility AND/OR
- Signs and Symptoms: suspicion of active TB disease (one or more criteria):
- Chest X-ray suggestive of TB: cavity AND/OR hilar/mediastinal lymph node enlarged AND/OR military pattern
- Weight loss or failure to thrive within the previous 3 months that, in the investigator's opinion, is not solely due to inadequate feeding; or to another non-TB cause.
Show all 24Show fewer
- Any cough combined with loss of weight
- Cough alone: duration of > 14 days
- Repeated episodes of fever within 14 days not responding to course of antibiotics AND positive TST or IGRA, (for malaria endemic areas: AND after malaria has been excluded by at least a negative rapid test)*
- Signs \& symptoms of extrapulmonary TB:
- Enlarged lymph nodes for > 2 weeks, not painful to palpation;
- Gibbus (especially of recent onset)
- Non-painful enlarged joint
- Pleural effusion
- Pericardial effusion
- CSF examination findings in line with TB meningitis with at least elevated protein and low glucose (in relation to serum glucose); OR signs and symptoms in line with TB meningitis/CNS TB if lumbar puncture is contraindicated, in the view of the investigator:
- At least one of the following two:
- palsy of oculomotoric nerves of recent onset
- focal neurological symptoms indicating elevated intracranial pressure OR CNS lesions, of recent onset
- AND/OR at least two of the following less specific signs of TB meningitis/CNS TB (for malaria endemic areas: AND a negative malaria rapid diagnostic test):
- Lethargy
- Convulsion
- Meningism (neck stiffness)
- Headache (*the requirement of negative MRDT may be dropped in agreement with the sponsor during study conduct.)
Who cannot join
- Critical condition (if study procedures seems like an undue risk to patient's life), such as hypovolemic shock or clinically relevant anaemia (tachypnoea, tachycardia)
- Body weight is less than 2 kg
- Children of 15 years of age or older
- Are currently receiving anti-TB drug(s): ideally, eligible patients should not have received any anti-TB treatment. In exceptions, up to three daily doses given since treatment start before first study blood draw are acceptable for study inclusion
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
Mozambique1 site
Centro de Investigação e Treino em Saúde da Polana Caniço
Maputo, PO.BOX 264
South Africa1 site
University of Cape Town Lung Institute (UCTLI)
Cape Town, Cape
About this study
Official title: Rapid and Accurate Diagnosis of Paediatric (RaPaed) TB - An AIDA (Assessment of Innovative Diagnostics and Algorithms for Early and Sensitive Detection of Acute TB) Platform Study
This study will serve as a platform to evaluate new diagnostics in children suspected to have TB, establish diagnostic performance (sensitivity and specificity) and calculate positive and negative predictive values in a real-life cohort.
Finally, this study will comprise the results of several tests in its database. This will allow simulation of diagnostic algorithms, that may be composed of screening (i.e. rule-out) tests together with confirmatory tests to maximize sensitivity and specificity.
Read the detailed description
Tuberculosis (TB) is a major cause of child morbidity and mortality in the world. There are an estimated one million new paediatric cases and at least 239.000 deaths per year. As childhood mortality on TB treatment is low at 1%, this highlights the fact that a large proportion of cases are never diagnosed and thereby never receive appropriate treatment.
The inability to correctly and timely diagnose paediatric TB is the main obstacle to controlling disease and preventing adverse outcomes, specifically among infants and young children, children with malnutrition, HIV infection, and drug-resistant TB. Paediatric samples, which are difficult to obtain, have small volumes and low bacterial burden, leading to the low sensitivity of currently applied diagnostic tests for TB, which are geared towards adults.
The World Health Organization has clearly stated that new and improved diagnostics for children are a top priority.
With RaPaed TB, the Sponsor (LMU) designed a project that is ideally suited to evaluate a range of novel diagnostics and sampling strategies in a population of symptomatic children with presumptive TB with a high likelihood of mycobacteriological confirmation of disease. The key aspects of this project are a multi-site collaboration of five geographically distinctive sites in highly TB endemic settings allowing a large sample size, and a high proportion of bacteriologically confirmed cases and making study findings generalizable.
Internationally recognized experts in child TB clinical research are included in the study; FIND's panel of diagnostic tests and expertise in diagnostics development and evaluation as well in the WHO submission and review process of the gathered data; LMU with its track record of delivering high-quality studies in the TB field; two large industry partners dedicated to the development of robust point-of-care assays; and finally, early involvement of National TB Programmes in the studies which will not only add to local capacity development, but also enable rapid local approval and uptake.
974 paediatric patients were enrolled into the RaPaed study in the four African and one Indian sites, with an average confirmation rate of 24% (study target: 25%).
Ten new diagnostic techniques suitable for children are being assessed in this study. These include a new stool protocol and Nasopharyngeal Aspirate for Xpert® MTB/RIF Ultra, TAM-TB from the University of Munich/Beckman Coulter Inc., a host biomarker panel by the University of Stellenbosch, host RNA tests, host protein biomarker tests (i.e. FIND and SomaLogic's host-response serum markers), and two novel urinary LAM tests (i.e. UriTB direct, FUJIFILM-urinary-LAM), and Cepheid's Fingerprick test.
It is realistic to think that this study will lead to WHO endorsement or recommendation of at least two or more new assays or sampling strategies; with FIND leading the WHO submission process which could therefore impact childhood TB policies globally.
In this third period of the RaPaed-TB study, all relevant study documents have been maintained such as the protocol, the Manual of Procedures, SOPs and Worksheets for collecting the data.
Ethics approval for the study conduct and all updates have been obtained centrally and in all study sites by the time of submission of this report.
The database has been maintained and updated, fulfilling its function for study data collection and analysis, as well as enabling study oversight and quality control.
- Conditions
- Tuberculosis, Diagnoses Disease
- Being tested
- Sample collection
- Keywords
- Tuberculosis, Paediatrics, Diagnostics
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sample collectionDiagnostic test
Specimen collection
| Study group | Role | What they receive |
|---|---|---|
| Paediatric diagnostic group | Paediatric diagnostic group Receives: Diagnostic Test: Sample collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity and Specificit of new test candidates; against a clinica/microbiological reference standard case definition
The case definition has been defined by an NIH-convened expert panel, published in 2012 and updated in 2015 (S. Graham et al.; CID). This definition describes the diagnostic certainty for a child to suffer from TB.
Possible classifications:
- Confirmed active tuberculosis
- Unconfirmed tuberculosis
- Unlikely tuberculosis
This case definition will be made based on the following:
- Confirmed active tuberculosis: bacteriological confirmation obtained (TB lab; positive culture AND/OR WHO endorsed PCR).
- Unconfirmed tuberculosis: bacteriological confirmation NOT obtained AND at least two of the following:
Symptoms suggestive of TB X-ray suggestive of TB Close exposure to TB Positive response to TB treatment
- Unlikely tuberculosis: defined as bacteriological confirmation NOT obtained AND criteria for "unconfirmed tuberculosis" NOT met
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2018
- Study start21 Jan 2019
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 974 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Hoelscher
- Sponsor type
- University, hospital or other
- Collaborators
- University of Cape Town Lung Institute, Instituto Nacional de Saúde, Mozambique, Kamuzu University of Health Sciences, Karolinska Institutet, Research Center Borstel, University of Stellenbosch, Beckman Coulter, Inc., Cepheid, Otsuka Novel Products GmbH, University of Melbourne, Foundation for Innovative New Diagnostics, Switzerland, National Institute for Medical Research, Tanzania, Christian Medical College, Vellore, India
- Responsible party
- Sponsor-investigator, Michael Hoelscher, Ludwig-Maximilians - University of Munich
- Investigators
- Michael Hoelscher, Professor, Principal investigator, University Hospital, LMU MunichNorbert Heinrich, MD, Study director, University Hospital, LMU Munich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03734172
- Sponsor's protocol ID
- LMU-IMPH-AIDA-02
- Acronym
- RaPaed
- Status last verified
- Apr 2023
- First submitted
- 22 Jun 2018
- Last updated
- 1 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Banze D, Olbrich L, Razid A, Franckling-Smith Z, Mfinanga A, Ntinginya NE, Sabi I, Nliwasa M, Semphere R, Corbett EL, Michael JS, Verghese VP, Graham SM, Nabeta P, Trollip A, Song R, Larsson L, Geldmacher C, Hoelscher M, Zar HJ, Viegas S, Heinrich N, Khosa C. Diagnostic performance of a centrifugation-free stool processing kit in conjunction with Xpert(R)MTB/RIF Ultra for paediatric tuberculosis: a multicentre prospective study in five low and middle-income countries. BMC Infect Dis. 2026 Aug 10;26(1):1736. doi: 10.1186/s12879-026-13902-6.
PubMed 42811307Olbrich L, Nliwasa M, Sabi I, Ntinginya NE, Khosa C, Banze D, Corbett EL, Semphere R, Verghese VP, Michael JS, Graham SM, Egere U, Schaaf HS, Morrison J, McHugh TD, Song R, Nabeta P, Trollip A, Geldmacher C, Hoelscher M, Zar HJ, Heinrich N; RaPaed-AIDA-TB Consortium. Rapid and Accurate Diagnosis of Pediatric Tuberculosis Disease: A Diagnostic Accuracy Study for Pediatric Tuberculosis. Pediatr Infect Dis J. 2023 May 1;42(5):353-360. doi: 10.1097/INF.0000000000003853. Epub 2023 Feb 16.
PubMed 36854097
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rapid and Accurate Diagnosis of Paediatric (RaPaed) TB - An AIDA (Assessment of Innovative Diagnostics and Algorithms for Early and Sensitive Detection of Acute TB) Platform Study
- ClinicalTrials.gov ID
- NCT03734172
- Acronym / sponsor ID
- RaPaed / LMU-IMPH-AIDA-02
- Conditions
- Tuberculosis, Diagnoses Disease
- Keywords
- Tuberculosis, Paediatrics, Diagnostics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 974 participants (actual)
- Lead sponsor
- Michael HoelscherUniversity, hospital or other
- Collaborators
- University of Cape Town Lung Institute, Instituto Nacional de Saúde, Mozambique, Kamuzu University of Health Sciences, Karolinska Institutet, Research Center Borstel, University of Stellenbosch, Beckman Coulter, Inc., Cepheid, Otsuka Novel Products GmbH, University of Melbourne, Foundation for Innovative New Diagnostics, Switzerland, National Institute for Medical Research, Tanzania, Christian Medical College, Vellore, India
- Study start
- 21 Jan 2019 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 7 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will serve as a platform to evaluate new diagnostics in children suspected to have TB, establish diagnostic performance (sensitivity and specificity) and calculate positive and negative predictive values in a real-life cohort.
Finally, this study will comprise the results of several tests in its database. This will allow simulation of diagnostic algorithms, that may be composed of screening (i.e. rule-out) tests together with confirmatory tests to maximize sensitivity and specificity.
Detailed description
Tuberculosis (TB) is a major cause of child morbidity and mortality in the world. There are an estimated one million new paediatric cases and at least 239.000 deaths per year. As childhood mortality on TB treatment is low at 1%, this highlights the fact that a large proportion of cases are never diagnosed and thereby never receive appropriate treatment.
The inability to correctly and timely diagnose paediatric TB is the main obstacle to controlling disease and preventing adverse outcomes, specifically among infants and young children, children with malnutrition, HIV infection, and drug-resistant TB. Paediatric samples, which are difficult to obtain, have small volumes and low bacterial burden, leading to the low sensitivity of currently applied diagnostic tests for TB, which are geared towards adults.
The World Health Organization has clearly stated that new and improved diagnostics for children are a top priority.
With RaPaed TB, the Sponsor (LMU) designed a project that is ideally suited to evaluate a range of novel diagnostics and sampling strategies in a population of symptomatic children with presumptive TB with a high likelihood of mycobacteriological confirmation of disease. The key aspects of this project are a multi-site collaboration of five geographically distinctive sites in highly TB endemic settings allowing a large sample size, and a high proportion of bacteriologically confirmed cases and making study findings generalizable.
Internationally recognized experts in child TB clinical research are included in the study; FIND's panel of diagnostic tests and expertise in diagnostics development and evaluation as well in the WHO submission and review process of the gathered data; LMU with its track record of delivering high-quality studies in the TB field; two large industry partners dedicated to the development of robust point-of-care assays; and finally, early involvement of National TB Programmes in the studies which will not only add to local capacity development, but also enable rapid local approval and uptake.
974 paediatric patients were enrolled into the RaPaed study in the four African and one Indian sites, with an average confirmation rate of 24% (study target: 25%).
Ten new diagnostic techniques suitable for children are being assessed in this study. These include a new stool protocol and Nasopharyngeal Aspirate for Xpert® MTB/RIF Ultra, TAM-TB from the University of Munich/Beckman Coulter Inc., a host biomarker panel by the University of Stellenbosch, host RNA tests, host protein biomarker tests (i.e. FIND and SomaLogic's host-response serum markers), and two novel urinary LAM tests (i.e. UriTB direct, FUJIFILM-urinary-LAM), and Cepheid's Fingerprick test.
It is realistic to think that this study will lead to WHO endorsement or recommendation of at least two or more new assays or sampling strategies; with FIND leading the WHO submission process which could therefore impact childhood TB policies globally.
In this third period of the RaPaed-TB study, all relevant study documents have been maintained such as the protocol, the Manual of Procedures, SOPs and Worksheets for collecting the data.
Ethics approval for the study conduct and all updates have been obtained centrally and in all study sites by the time of submission of this report.
The database has been maintained and updated, fulfilling its function for study data collection and analysis, as well as enabling study oversight and quality control.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Paediatric diagnostic group | – | Diagnostic Test: Sample collectionPaediatric diagnostic group |
Who may qualify
- Ages
- Up to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Patients 14 years old or younger with a suspicion of active TB are eligible for recruitment into the study, if they meet the specified inclusion criteria, and none of the exclusion criteria.
Key inclusion criteria (24 listed)
- Consent and Assent (if applicable): signed written consent/assent, or witnessed oral consent/assent in the case of illiteracy, before undertaking any study-specific activity. The age threshold for child assent requirement will be laid down in each the Investigator Site File based on the local Ethics Committee requirement.
- Confirmation of TB disease: microbiological confirmation of active TB disease by positive smear AND/OR culture AND/OR PCR (e.g. GeneXpert®); e.g. in a non-study health facility AND/OR
- Signs and Symptoms: suspicion of active TB disease (one or more criteria):
- palsy of oculomotoric nerves of recent onset
- focal neurological symptoms indicating elevated intracranial pressure OR CNS lesions, of recent onset
Key exclusion criteria (4 listed)
- Critical condition (if study procedures seems like an undue risk to patient's life), such as hypovolemic shock or clinically relevant anaemia (tachypnoea, tachycardia)
- Body weight is less than 2 kg
- Children of 15 years of age or older
- Are currently receiving anti-TB drug(s): ideally, eligible patients should not have received any anti-TB treatment. In exceptions, up to three daily doses given since treatment start before first study blood draw are acceptable for study inclusion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sample collectionSpecimen collection | Diagnostic test | Paediatric diagnostic group |
Primary outcome
Sensitivity and Specificit of new test candidates; against a clinica/microbiological reference standard case definition
Time frame: 6 months
The case definition has been defined by an NIH-convened expert panel, published in 2012 and updated in 2015 (S. Graham et al.; CID). This definition describes the diagnostic certainty for a child to suffer from TB. Possible classifications: * Confirmed active tuberculosis * Unconfirmed tuberculosis * Unlikely tuberculosis This case definition will be made based on the following: * Confirmed active tuberculosis: bacteriological confirmation obtained (TB lab; positive culture AND/OR WHO endorsed PCR). * Unconfirmed tuberculosis: bacteriological confirmation NOT obtained AND at least two of the following: Symptoms suggestive of TB X-ray suggestive of TB Close exposure to TB Positive response to TB treatment • Unlikely tuberculosis: defined as bacteriological confirmation NOT obtained AND criteria for "unconfirmed tuberculosis" NOT met
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2023.
- Derived from this study: PubMed 42811307Banze D, Olbrich L, Razid A, Franckling-Smith Z, Mfinanga A, Ntinginya NE, Sabi I, Nliwasa M, Semphere R, Corbett EL, Michael JS, Verghese VP, Graham SM, Nabeta P, Trollip A, Song R, Larsson L, Geldmacher C, Hoelscher M, Zar HJ, Viegas S, Heinrich N, Khosa C. Diagnostic performance of a centrifugation-free stool processing kit in conjunction with Xpert(R)MTB/RIF Ultra for paediatric tuberculosis: a multicentre prospective study in five low and middle-income countries. BMC Infect Dis. 2026 Aug 10;26(1):1736. doi: 10.1186/s12879-026-13902-6.
- Derived from this study: PubMed 36854097Olbrich L, Nliwasa M, Sabi I, Ntinginya NE, Khosa C, Banze D, Corbett EL, Semphere R, Verghese VP, Michael JS, Graham SM, Egere U, Schaaf HS, Morrison J, McHugh TD, Song R, Nabeta P, Trollip A, Geldmacher C, Hoelscher M, Zar HJ, Heinrich N; RaPaed-AIDA-TB Consortium. Rapid and Accurate Diagnosis of Pediatric Tuberculosis Disease: A Diagnostic Accuracy Study for Pediatric Tuberculosis. Pediatr Infect Dis J. 2023 May 1;42(5):353-360. doi: 10.1097/INF.0000000000003853. Epub 2023 Feb 16.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Hoelscher, Professor principal investigator
University Hospital, LMU Munich
Norbert Heinrich, MD study director
University Hospital, LMU Munich
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis and Diagnoses Disease, run by Michael Hoelscher at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in India, Malawi, Mozambique, South Africa, Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity and Specificit of new test candidates; against a clinica/microbiological reference standard case definition (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03734172, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2023.