Clinical trial NCT04899076: Stool Processing Kit (SPK) Evaluation for Pediatric Tuberculosis (TB)
Official title: Multicentre Study to Evaluate the Diagnostic Accuracy of a Stool Processing Kit Combined With Xpert MTB/RIF Ultra for Paediatric TB Diagnosis Using Microbiological Confirmation on Respiratory Samples as the Reference Standard
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Tuberculosis
Keywords: Diagnostics
Children
Lead sponsor: Foundation for Innovative New Diagnostics, Switzerland
Sponsor class: OTHER
Collaborators: name: Mulago Hospital, Uganda
name: University of Cape Town Lung Institute
name: University of California, San Francisco
name: All India Institute of Medical Sciences
name: KEM Hospital Research Centre
First posted: 2021-05-24
Enrollment: 600
Sex: ALL
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children who are 14 years of age or younger who present with signs and symptoms of pulmonary TB, or have microbiological confirmation of active tuberculosis (TB) and are referred to enrollment sites

Brief summary: This is a prospective, multicenter cohort study in which the accuracy and the diagnostic yield of the Stool Processing Kit (SPK) in combination with Xpert Ultra MTB/RIF (Ultra) on stool samples will be assessed using a microbiological reference standard and a composite reference standard among children with signs and symptoms of pulmonary tuberculosis.

Detailed description: FIND and partners have developed a simple Stool Processing Kit (SPK) that will enable processing of large numbers of stool samples, removal of PCR (polymerase chain reaction) inhibitors which can be used at level 1 health facilities in low and middle income countries.

The SPK is not a diagnostic kit as such but rather a sample processing method. This study aims to determine the sensitivity and specificity of Xpert Ultra MTB/RIF (Ultra) combined with SPK for TB detection using microbiological confirmation on respiratory specimens (defined as sputum, naso-pharyngeal aspirate, and/or gastric aspirate) as the reference standard. The investigators will further evaluate operational characteristics, including implementation considerations that will be needed for the potential rollout of the SPK.

Additionally, a comparison of the performance of the SPK with up to two other centrifuge-free stool processing methods will be done on the same stool samples. The first is a method developed by researchers at the KNCV Tuberculosis Foundation (Single One Step Stool) which does not require any additional reagents other than the Ultra Sample Reagent. The second is a method developed by the Pediatric Asian African Network for Tuberculosis and HIV Research (PANTHER) group, the Optimized Sucrose Flotation method. Another diagnostic candidate, the urine Fujifilm SILVAMP TB LAM (FujiLAM) test will be assessed during the study.

Therefore, if the sensitivity of any of these tests is shown to be promising this may support further research and provide other alternatives to respiratory samples.

Eligibility criteria: Inclusion Criteria:

* Children of 14 years of age or younger
* Written parent/guardian consent and child assent based on age and national ethical guidelines
* Willingness to have a study follow-up visit
* Clinical suspicion of active pulmonary TB\* OR microbiological confirmation of active TB disease referred from non-study health facilities

  * Chest X-ray suggestive of TB, or weight loss or failure to thrive within 3 months not solely due to inadequate feeding, or another non-TB cause, or any cough with loss of weight, or cough alone \>=14 days, or persistent (\>1 week) and unexplained fever

Exclusion Criteria:

* Anti-TB treatment for \>5 days or any antibiotic with anti-mycobacteria activity within 60 days prior to enrollment including children on Isoniazid Preventive Therapy
* (confirmed) extra-pulmonary TB only

Primary outcomes:
measure: Sensitivity and specificity of a single Ultra/SPK using microbiological confirmation on respiratory specimens as reference standard
timeFrame: 2 months
Secondary outcomes:
measure: Diagnostic accuracy of a single Ultra/SPK using the National Institutes of Health (NIH) consensus definition as reference standard
timeFrame: 2 months
measure: Diagnostic accuracy of a single Ultra/SPK for Rifampin resistance detection
timeFrame: 2 months
measure: Additional yield (increase in sensitivity) of a 2nd Ultra/SPK
timeFrame: 2 months
measure: Diagnostic accuracy of a single Ultra/SPK for TB detection per subgroup
timeFrame: 2 months
measure: Diagnostic accuracy of additional interventions: Simple One Step (SOS), Optimized Sucrose Flotation (OSF) and Fujifilm SILVAMP TB LAM
timeFrame: 2 months
measure: Feasibility and user appraisal of the different stool processing methods
timeFrame: 6 months
Other outcomes:
Locations:
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
city: Pune
country: India
facility: KEM Hospital Research Centre
city: Cape Town
country: South Africa
facility: University of Cape Town Lung Institute
city: Kampala
country: Uganda
facility: Mulago Hospital
Study officials:
affiliation: Find
name: Morten Ruhwald, MD
role: STUDY_DIRECTOR
References: