Rapid and Accurate Diagnosis of Paediatric TB (RaPaed-AIDA-TB)

NCT03734172 | Completed DMC

• 1 other identifier: LMU-IMPH-AIDA-02
• Study Type: observational
• Target: 974
• Locations: 5 countries
• Sites: 5

Brief 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. 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.

Conditions

Tuberculosis; Diagnoses Disease

Keywords

Tuberculosis; Paediatrics; Diagnostics

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Other Outcomes (2)

• Ability of new tests to measure response to TB treatment, by measuring the change in experimental test readout over time while receiving TB treatment

  6 months

• Proportion of children with confirmed TB, and with other diseases, who have acute and chronic lung impairment using spirometry

  12 months

Study Arms (1)

Paediatric diagnostic group

Paediatric diagnostic group

Diagnostic Test: Sample collection

Interventions

Sample collection DIAGNOSTIC_TEST

Specimen collection

Paediatric diagnostic group

Eligibility Criteria

• Age: Up to 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Michael Hoelscher: lead
• University of Cape Town Lung Institute: collaborator
• Instituto Nacional de Saúde, Mozambique: collaborator
• Kamuzu University of Health Sciences: collaborator
• Karolinska Institutet: collaborator
• Research Center Borstel: collaborator
• University of Stellenbosch: collaborator
• Beckman Coulter, Inc.: collaborator
• Cepheid: collaborator
• Otsuka Novel Products GmbH: collaborator
• University of Melbourne: collaborator
• Foundation for Innovative New Diagnostics, Switzerland: collaborator
• National Institute for Medical Research, Tanzania: collaborator
• Christian Medical College, Vellore, India: collaborator

Study Sites (5)

Christian Medical College

Vellore, Tamil Nadu, 632004, India

Location

University of Malawi College of Medicine

Blantyre, Malawi

Location

Centro de Investigação e Treino em Saúde da Polana Caniço

Maputo, PO.BOX 264, Mozambique

Location

University of Cape Town Lung Institute (UCTLI)

Cape Town, Cape, South Africa

Location

NIMR - Mbeya Medical Research Programme

Mbeya, P.O. Box 2410, Tanzania

Location

Related Publications (1)

• Olbrich 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.

  PMID: 36854097 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Molecular speciation test; Mycobacterial DNA extraction will be performed centrally on stored samples and will be further analysed using classical molecular MTB typing methods (genotyping) as well as by next generation sequencing (genome sequencing).

MeSH Terms

Conditions

Tuberculosis

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Michael Hoelscher, Professor

  University Hospital, LMU Munich

  PRINCIPAL INVESTIGATOR

• Norbert Heinrich, MD

  University Hospital, LMU Munich

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof Dr med / Sponsor Responsible Person

Study Record Dates

• First Submitted: June 22, 2018
• First Posted: November 7, 2018
• Study Start: January 21, 2019
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: May 1, 2023

Record last verified: 2023-04

Locations

TA (1); MA (1); ZA (1); IN (1); MO (1)