Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202006814433059 Date of Approval: 08/06/2020
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title TB-Speed - Stool Processing
Official scientific title Evaluation of four stool processing methods combined with Xpert MTB/RIF Ultra for diagnosis of intrathoracic Paediatric TB
Brief summary describing the background and objectives of the trial There is a growing interest for the use of stool samples as an alternative to respiratory samples for the diagnosis of intrathoracic TB in children unable to produce sputum. Unlike respiratory samples, stool samples require processing before molecular testing. Several groups have already evaluated different processing methods. However, it is difficult to know which method has the best accuracy and potential for use at Primary Health Care level, due to the difference in study designs and populations. Therefore, in this study, the investigators propose to evaluate the accuracy of different promising stool processing methods in the same population within the same study with an adapted design. Furthermore, no study has so far evaluated for stool testing the new Xpert MTB/RIF Ultra cartridge that has a lower level of detection than the previous Xpert MTB/RIF cartridge. The investigators propose to evaluate the accuracy of Xpert MTB/RIF Ultra performed on stool samples collected from children with presumptive TB and processed using four different processing methods (Standard sucrose flotation method, optimized sucrose flotation method, SPK, and SOS) against bacteriological results from respiratory specimens and to perform a head-to-head comparison of the diagnostic accuracy and feasibility of these different methods. The selection of processing methods was based on accuracy results, degree of simplification allowing their introduction at PHC level, and finding from the TB-Speed in-vitro stool processing study. This is a diagnostic study evaluating the diagnostic accuracy of the Ultra assay in stools with a two-stage sequential design starting as a cohort of children with presumptive TB enriched in a second stage with Ultra positive cases on respiratory sample. It is both an ancillary to the TB-Speed HIV and TB-Speed SAM studies and a study enrolling children from routine not enrolled in those two studies.
Type of trial CCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations,Paediatrics,Respiratory
Sub-Disease(s) or condition(s) being studied Tuberculosis
Purpose of the trial Diagnosis / Prognosis
Anticipated trial start date 06/01/2020
Actual trial start date 13/01/2020
Anticipated date of last follow up 06/07/2021
Actual Last follow-up date 07/02/2022
Anticipated target sample size (number of participants) 274
Actual target sample size (number of participants) 215
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
C19.34 Inserm
NCT04203628 ClinicalTrials.gov
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Prospective cohort 2 months Any child with presumptive TB will be proposed to participate in the study. For children identified from the routine practice, the nurse will collect 2 respiratory samples (sputum or GA) in consecutive children with presumptive TB to be tested using Ultra as done in routine care, record symptoms and refer the child for clinical exam and for chest X-ray. For the purpose of the study, 2 stool samples will be collected to be tested with Ultra. In addition, for study purpose the two respiratory samples will be tested with Mycobacterial culture as this test is not routinely prescribed for TB diagnosis in the study sites If the child is enrolled in the TB-Speed SAM or HIV studies, the study nurse will collect 2 stool samples then collect information about the clinical examination, chest X-ray, HIV-testing and the mycobacterial culture results as soon as they are available, from the data collected in the TB-speed records since all these procedures are already performed in these studies. The Xpert MTB/Rif Ultra diagnosis test will be performed on stool samples processed using four different processing methods(Standard sucrose flotation method, Optimized sucrose flotation, Stool processing kit (SPK), Simple One-step method (SOS)) and on gastric aspirate or expectorated sputum 177
Experimental Group Enrichment cohort 2 months Any child with presumptive TB and a positive Xpert result from one respiratory sample (NPA, IS or GA) will be proposed to participate in the study. For children identified from the routine care, once enrolled, samples collected as routine practice will be tested with mycobacterial culture in addition to Xpert. If needed an additional respiratory sample will be collected (sputum or GA) and tested with Mycobacterial culture. The nurse will also record symptoms, refer the child for clinical exam and for chest X-ray, and collect stool samples. HIV-testing will be offered for children with unknown HIV status. If the child is enrolled in the TB-Speed SAM or HIV studies, the study nurse will collect 2 stool samples then collect information about the clinical examination, chest X-ray, HIV-testing and the mycobacterial culture results as soon as they are available, from the data collected in the TB-speed records since all these procedures are already performed in these studies. The Xpert MTB/Rif Ultra will be performed on stool samples processed using four different processing methods: Standard sucrose flotation method, Optimized sucrose flotation, Stool processing kit (SPK) and Simple One-step method (SOS) 77
Control Group No control arm in this study 0 No control arm in this study 0 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
For the prospective cohort: Children < 15 years old Presumptive intra-thoracic TB based on at least one criterion among the following: - Persistent cough for more than 2 weeks - Persistent fever for more than 2 weeks - Recent failure to thrive (documented clear deviation from a previous growth trajectory in the last 3 months or Z score weight/age < 2) - Failure of broad-spectrum antibiotics for treatment of pneumonia - Suggestive CXR features - OR History of contact with a TB case and any of the symptoms listed under point 2 with shorter duration (< 2 weeks) if the child is HIV infected or presents with SAM. Signed informed consent by parent or guardian and assent signed by children ≥ 7 years old For the enrichment cohort: Children < 15 years old Presumptive TB based on at least one criterion among the following: - Persistent cough for more than 2 weeks - Persistent fever for more than 2 weeks - Recent failure to thrive (documented clear deviation from a previous growth trajectory in the last 3 months or Z score weight/age < 2) - Failure of broad-spectrum antibiotics for treatment of pneumonia - Suggestive CXR features - OR History of contact with a TB case and any of the symptoms listed under point 2 with shorter duration (< 2 weeks) if the child is HIV infected or presents with SAM One positive Xpert (MTB/Rif or Ultra) result from at least one respiratory sample: sputum, NPA or GA Signed informed consent by parent or guardian and assent signed by children ≥ 7 years old > 5 days of antituberculosis treatment in the last 3 months History of tuberculosis preventive therapy in the last 3 months Confirmed extrapulmonary TB only Adolescent: 13 Year-18 Year,Child: 6 Year-12 Year,Infant: 0 Month-23 Month,Infant: 1 Month-23 Month,New born: 0 Day-1 Month,Preschool Child: 2 Year-5 Year 0 Day(s) 15 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 06/09/2019 MUST REC
Ethics Committee Address
Street address City Postal code Country
Kabale Mbarara Road Mbarara 1410 Uganda
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 29/08/2019 UNZA Biomedical research ethics committee
Ethics Committee Address
Street address City Postal code Country
Ridgeway Campus Lusaka 50110 Zambia
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 16/10/2019 WHO ERC
Ethics Committee Address
Street address City Postal code Country
20 Avenue Appia Geneva 1202 Switzerland
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 27/06/2019 Comite dEvaluation Ethique de lInserm
Ethics Committee Address
Street address City Postal code Country
101 rue de Tolbiac Paris 75013 France
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Sensitivity and sensibility of Ultra on stool using TB culture reference standard (Löwenstein–Jensen medium and Mycobacteria Growth Indicator Tube) in two respiratory samples (two sputums or two gastric aspirates according the age of the child). 8 weeks
Secondary Outcome Sensitivities and specificities of each sampling method - Sensitivities and specificities of each sampling method using TB culture reference standard - Sensitivities and specificities of each sampling method using the Clinical Case Definition for Classification of Intrathoracic Tuberculosis in Children 8 weeks
Secondary Outcome Proportion of Ultra "trace" results in stools out of the number of stools tested with Ultra 8 weeks
Secondary Outcome Proportion of Ultra semi-quantitative results "very low"; "low"; "medium" and "high" in stool 8 weeks
Secondary Outcome Proportion of invalid Ultra results from stool out of the number of stools tested with Ultra 8 weeks
Secondary Outcome Proportion of Rifampicin resistant results on Ultra (stool and respiratory), line probe assay and drug-susceptibility testing 8 weeks
Secondary Outcome Proportion of children successfully providing a stool sample 8 weeks
Secondary Outcome Relative gain of the 2nd stool sample as compared to the 1st one as measured by the number of additional positive results obtained from the addition of the 2nd sample as compared to the results of the first sample only 8 weeks
Secondary Outcome Feasibility assessment of the stool processing methods by laboratory technician 14 months
Secondary Outcome Per-protocol analysis of sensitivities and specificities of Ultra on stool using TB culture reference standard (LJ ans MGIT) in respiratory sample, excluding invalid Ultra results and contaminated culture results from analysis. 8 weeks
Secondary Outcome Stratification of characteristics and laboratory results by age groups (≤2 years and > 2 years) 8 weeks
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
University Teaching Hospital Childrens Hospital Nationalist Road Lusaka Zambia
Mbarara Regional Referral Hospital Kabale - Mbarara Road Mbarara Uganda
Arthur Davidson Children Hospital Chiwanangala Rd Ndola Zambia
FUNDING SOURCES
Name of source Street address City Postal code Country
UNITAID Global Health Campus, Chemin du Pommier 40 Geneva Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor INSERM 8 rue de la croix Jarry Paris 75013 France Public Research Institute
COLLABORATORS
Name Street address City Postal code Country
IRD French National Research Institute for Sustainable Development 911 Avenue Agropolis Montpellier France
University of Bordeaux 146 rue Leo Saignat Bordeaux France
MUJHU Research Collaboration MUJHU CARE LTD Upper Mulago Hill Road Kampala Uganda
Epicentre Mbarara Research Centre Kabale - Mbarara road Mbarara Uganda
University of Zambia School of Medecine UTH Nationalist Road Luzaka Zambia
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Maryline Bonnet maryline.bonnet@ird.fr +33467416491 911 Avenue Agropolis
City Postal code Country Position/Affiliation
Montpellier France Coordinating Invetigator
Role Name Email Phone Street address
Public Enquiries Manon Lounnas manon.lounnas@ird.fr +33467416391 911 Avenue Agropolis
City Postal code Country Position/Affiliation
Montpellier France International project manager
Role Name Email Phone Street address
Scientific Enquiries Maryline Bonnet maryline.bonnet@ird.fr +33467416491 911 Avenue Agropolis
City Postal code Country Position/Affiliation
Montpellier France Coordinating investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data will be available after de-identification Informed Consent Form,Statistical Analysis Plan,Study Protocol Access to data will be given after the publication of the main study results based on global data. Data can be requested by members or partners of the TB-Speed consortium or by external research groups. They can be used for secondary analyses of the TB-Speed project, country specific analyses, contribution to individual data meta-analysis and analyses that are not related to the research thematic of TB-Speed project. The request for access to data will need to be sent to the Publication Committee accompanied by a concept paper describing the objectives of the analysis/study, how the data will be used, the list of data or material requested and how the original contributors will be credited. Once the application is approved, data will be released under a data and/or material sharing agreement that secures the term of use.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information