Stool Processing Kit (SPK) Evaluation for Paediatric TB

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

This is a prospective, multicentre 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Tuberculosis
• Intervention / Treatment: Device: Stool Processing Kit

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 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, nasopharyngeal aspirate, and/or gastric aspirate) as the reference standard. We will further evaluate operational characteristics, including implementation considerations that will be needed for the potential roll out of the SPK.

Additionally, a comparison of the performance of the SPK with up to two other cnetrifuge-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 Paediatric Asian African Network for Tuberculosis and HIV Research (PAANTHER) 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.

• Study Type: Observational
• Enrollment (Actual): 600

Contacts and Locations

Study Locations

• India
  • New Delhi, India
    • All India Institute of Medical Sciences
  • Pune, India
    • KEM Hospital Research Centre
• South Africa
  • Cape Town, South Africa
    • University of Cape Town Lung Institute
• Uganda
  • Kampala, Uganda
    • Mulago Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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 TB and are referred to enrollment sites

Description

Inclusion Criteria:

Children of 14 years of age or younger + written parent/guardian consent + child assent based on age and national ethical guidelines + willingness to have a study follow-up visit + [clinical suspicion of active pulmonary TB* (irrespective of extra-pulmonary disease) OR microbiological confirmation of active TB disease referred from non-study health facilities].

*CXR 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-mycobacterial activity within 60 days prior to enrolment including children on IPT, OR (confirmed) extrapulmonary TB only

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity of a single Ultra/SPK using microbiological confirmation on respiratory specimens as reference standard	Point estimates of sensitivity and specificity with 95% confidence intervals, using microbiological confirmation including two cultures and two Xpert MTB/RIF Ultra in respiratory samples	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy of a single Ultra/SPK using the NIH classification as reference standard	Point estimates of sensitivity and specificity with 95% confidence intervals, using the Revised Classification NIH classification for diagnostic evaluation studies in children (S. Graham et al.; CID)	2 months
Diagnostic accuracy of a single Ultra/SPK for RIF resistance detection	Point estimates of sensitivity and specificity with 95% confidence intervals, with phenotypic MGIT DST on respiratory specimens as reference standard	2 months
Additional yield (increase in sensitivity) of a 2nd Ultra/SPK	Sensitivity of a 2nd sampling on the same stool with Ultra/SPK for TB and RIF resistance detection using the different reference standards (Outcome 1 & 2)	2 months
Diagnostic accuracy of a single Ultra/SPK for TB detection per subgroup	Sensitivity and specificity of Ultra/SPK by sample, by site, by smear grade, by HIV status, by TB history, by stool consistency, and by age using the different reference standards (Outcome 1 & 2)	2 months
Diagnostic accuracy of additional interventions: Simple One Step (SOS), Optimized Sucrose Flotation (OSF) and Fujifilm SILVAMP TB LAM	Sensitivity and specificity, by intervention using the different reference standards (Outcome 1 & 2) and by subgroup (Outcome 5)	2 months
Feasibility and user appraisal of the different stool processing methods	Assessment of user appraisal on ease of use and potential implementation of stool processing methods using a standardized questionnaire	6 months

Collaborators and Investigators

• Sponsor: Foundation for Innovative New Diagnostics, Switzerland
• Collaborators: All India Institute of Medical Sciences, New Delhi; University of California, San Francisco; University of Cape Town Lung Institute; KEM Hospital Research Centre; Mulago Hospital, Uganda
• Investigators: Study Director: Morten Ruhwald, MD, Find

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2019
• Primary Completion (Actual): March 31, 2021
• Study Completion (Anticipated): October 19, 2021

Study Registration Dates

• First Submitted: May 19, 2021
• First Submitted That Met QC Criteria: May 19, 2021
• First Posted (Actual): May 24, 2021

Study Record Updates

• Last Update Posted (Actual): May 24, 2021
• Last Update Submitted That Met QC Criteria: May 19, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Children; Diagnostics
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: 7210-07-2/1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No