Diagnosis of Tuberculosis in Swiss Children

• Conditions: Tuberculosis; Mycobacterium Tuberculosis
• Interventions: Diagnostic Test: Secreted cytokine assay; Diagnostic Test: Intracellular cytokine assay

• Registration Number: NCT03044509
• Lead Sponsor: University Children's Hospital Basel

Brief Summary

1. The primary objective is to improve the sensitivity of novel immunodiagnostic tests for detection of TB disease in children.

2. The secondary objective is to determine biomarkers that discriminate children with TB infection and disease.

Detailed Description

1. This will be done by measuring a variety of parameters in the blood samples and compare them with the current diagnostic gold standard for TB or for culture/NAAT non-confirmed TB cases a consensus case definition is used.

Currently available immunodiagnostic tests (IGRA/TST) will be compared to novel immunodiagnostic tests which will include:

* several novel, additional M. tuberculosis-specific Antigens

* cytokines that are highly expressed

2. Since there is no diagnostic gold standard for TB infection we will rely on a clinical composite reference standard for diagnosing TB infection. Biomarkers will be determined by:

* including M. tuberculosis-specific antigens that are specifically expressed in either TB infection or disease,

* measuring phenotypes and cytokine production of M. tuberculosis-specific cells.

Study Timeline

• Study First Submitted: 2017-02-03
• Study First Submitted QC: 2017-02-03
• Study First Posted: 2017-02-07
• Study Start: 2017-05-12
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-16
• Last Update Posted: 2022-05-17
• Primary Completion: 2022-12
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 190

Inclusion Criteria

• all children / adolescents < 18 years of age undergoing evaluation for TB exposure, infection or disease.

Exclusion Criteria

• children / adolescents with TB infection or disease who have already been started on anti-mycobacterial treatment, children who have been treated for TB previously.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
TB exposure	Intracellular cytokine assay	-
TB exposure	Secreted cytokine assay	-
TB infection (latent TB)	Secreted cytokine assay	-
TB infection (latent TB)	Intracellular cytokine assay	-
TB disease (active TB)	Secreted cytokine assay	-
TB disease (active TB)	Intracellular cytokine assay	-

Primary Outcome Measures

Name	Time	Method
Improvement of immunodiagnostic tests for TB in children.	27 months	Based on current evidence it is estimated that the sensitivity of the immunodiagnostic tests with regard to the identification of patients with TB infection or disease versus no TB is approximately 80 %. By applying a sample size approximation a minimum sample size of 126 patients with TB infection or disease (with a precision given by a 95 % confidence interval with a width of 20 %) will be needed to statistically show a significant result.

Secondary Outcome Measures

Name	Time	Method
Indicative markers identification for TB infection and disease distinction	27 months	A minimum sample size of 84 patients with TB infection is needed (with a precision given by a 95 % confidence interval with a width of 30 %). Among patients with TB infection or TB disease, a novel test is used to discriminate between these patient groups. It is estimated that the sensitivity of this test with regard to the identification of patients with TB infection (secondary outcome) is approximately 60 %.

Trial Locations

Locations (8)

Nina Vaezipour; 🇨🇭 Basel, Switzerland

Kantonspital Aarau; 🇨🇭 Aarau, Switzerland

Ospedale Regionale di Bellinzona; 🇨🇭 Bellinzona, Switzerland

Inselspital Bern; 🇨🇭 Bern, Switzerland

Hôpital des enfants - HUG; 🇨🇭 Genève, Switzerland

Kinserspital Luzern; 🇨🇭 Luzern, Switzerland

Kinderspital St Gallen; 🇨🇭 St. Gallen, Switzerland

Kinderklinik Zürich; 🇨🇭 Zürich, Switzerland