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

Tuberculosis Clinical Trial

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

Status Completed

Clinical 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. 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Diagnoses Disease
• Disease
• Tuberculosis

• NCT number: NCT03734172
• Study type: Observational
• Source: Ludwig-Maximilians - University of Munich
• Status: Completed
• Start date: January 21, 2019
• Completion date: December 31, 2022