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.: PACTR202101615120643 Date of Approval: 21/01/2021
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title TB-Speed Pneumonia
Official scientific title Impact of Systematic Early Tuberculosis Detection Using Xpert MTB/RIF Ultra in Children With Severe Pneumonia in High Tuberculosis Burden Countries
Brief summary describing the background and objectives of the trial Despite progress in reducing tuberculosis (TB) incidence and mortality in the past 20 years, TB is a top ten cause of death in children under 5 years worldwide. However, childhood TB remains massively underreported and undiagnosed, mostly because of the challenges in confirming its diagnosis due to the paucibacillary nature of the disease and the difficulty in obtaining expectorated sputum in children. Pneumonia is the leading cause of death in children under the age of 5 years worldwide. There is growing evidence that, in high TB burden settings, TB is common in children with pneumonia, with up to 23% of those admitted to hospital with an initial diagnosis of pneumonia later being diagnosed as TB. However, the current WHO standard of care (SOC) for young children with pneumonia considers a diagnosis of TB only if the child has a history of prolonged symptoms or fails to respond to antibiotic treatments. Hence, TB is often under-diagnosed or diagnosed late in children presenting with pneumonia. In this context, the investigators are proposing to assess the impact on mortality of adding the systematic early detection of TB using Xpert MTB/RIF Ultra, performed on NPAs and stool samples, to the WHO SOC for children with severe pneumonia, followed by immediate initiation of anti-TB treatment in children testing positive on any of the samples. TB-Speed Pneumonia is a multicentric, stepped wedge diagnostic trial conducted in six countries with high TB incidence: Cote d'Ivoire, Cameroon, Uganda, Mozambique, Zambia and Cambodia The sub-study on Covid-19 will assess the prevalence and impact of the Covid-19 in young children hospitalized with severe pneumonia. The sub-study findings are expected to guide policy makers and clinicians on potential specific screening and management measures for these vulnerable groups of children. They are also key to analysing TB-Speed Pneumonia results on mortality in a context of the Covid-19 outbreak and to take into consideration SARS-
Type of trial RCT
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 Early detection /Screening
Anticipated trial start date 20/03/2019
Actual trial start date 20/03/2019
Anticipated date of last follow up 20/11/2020
Actual Last follow-up date 30/06/2021
Anticipated target sample size (number of participants) 3780
Actual target sample size (number of participants) 2570
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
C18.26 Inserm
NCT03831906 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
Crossover: all participants receive all interventions in different sequence during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group WHO Standard of Care 18 months All children admitted in the hospital and presenting with WHO-defined severe pneumonia will be immediately managed as part of routine care per the WHO Standard of Care (SOC), including broad spectrum antibiotics, oxygen therapy if required, additional supportive care and specific therapies for comorbidities such as HIV infection. For research purposes, children will benefit from HIV testing, malaria testing, and complete blood count (CBC) if not systematically performed as routine care in the country/hospital, as well as from a digitalized chest X-ray (CXR). Additionally, samples will be collected for future biomarkers studies (biobank). 1890 Active-Treatment of Control Group
Experimental Group TB Speed intervention 18 months Children will benefit from the WHO SOC and additional strategies for research purposes (HIV and malaria testing, CBC, CXR, and biobank) as described in the control arm, plus the study intervention. The intervention will consist of the WHO standard of care for children with severe pneumonia plus the study intervention consisting in rapid detection of TB on the day of hospital admission using the Ultra assay performed on 1 NPA and 1 stool sample. The sample flow will be organised to reduce time-to-results to 3 hours. Ultra will be performed at the hospital laboratory using a standard GeneXpert device, or implemented directly inward using a one-module, battery-operated GeneXpert device (G1 Edge). Drugs will be available at the inpatient level to enable immediate initiation of TB treatment, as soon as a positive Ultra result is available. 1890
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Children aged 2 to 59 months 2. Newly hospitalized for severe pneumonia defined using WHO criteria as cough or difficulty in breathing with: o Peripheral oxygen saturation < 90% or central cyanosis, or o Severe respiratory distress (e.g. grunting, nasal flaring, very severe chest indrawing), or o Signs of pneumonia, defined as cough or difficulty in breathing with fast breathing (tachypnea)2 and/or chest indrawing, with any of the following danger signs: a) Inability to breastfeed or drink, b) Persistent vomiting c) Lethargy or reduced level of consciousness d) Convulsions, e) Stridor in calm child f) Severe malnutrition 3. Informed consent signed by parent/guardian Ongoing TB treatment or history of intake of anti-TB drugs in the last 6 months Infant: 1 Month-23 Month,Preschool Child: 2 Year-5 Year 2 Month(s) 59 Month(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 19/12/2018 WHO Research Ethics Review Comittee
Ethics Committee Address
Street address City Postal code Country
20 Avenue Appia Geneva, CH 1211 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 14/02/2019 Comite National dEthique de la Recherche pour la Sante Humaine
Ethics Committee Address
Street address City Postal code Country
Rue 3038 quartier du Lac Yaounde 000000 Cameroon
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 31/12/2018 National Ethics Committee for Health Research
Ethics Committee Address
Street address City Postal code Country
28 Samdach Penn Nouth Boulevard Phnom Penh 120209 Cambodia
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 28/02/2019 Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
8 rue de la Croix Jarry PARIS 75013 France
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome All-cause mortality 12 weeks post-inclusion
Secondary Outcome 1. Number of children diagnosed with TB at 12 weeks: - based on Ultra results - based on the clinician's judgement 12 weeks
Secondary Outcome 2. Proportion of children with TB treatment initiated at any time during follow-up 12 weeks
Secondary Outcome 3. Time to TB treatment initiation 12 weeks
Secondary Outcome 4. Duration of TB treatment at end of trial, i.e. week 12 or early termination 12 weeks
Secondary Outcome 5. Number of inpatient deaths 12 weeks
Secondary Outcome 6. Duration of initial hospitalization 12 weeks
Secondary Outcome 7. Number of readmissions following discharge 12 weeks
Secondary Outcome 8. Weight gain at 12 weeks, as compared to body weight at inclusion 12 weeks
Secondary Outcome 9. In the intervention arm only - Proportion of NPA and stool samples with positive TB detection using Ultra 12 weeks
Secondary Outcome 10. In the intervention arm only - Proportion of Ultra-confirmed and clinically-diagnosed TB cases 12 weeks
Secondary Outcome 11. In the intervention arm only - Feasibility of NPA and stool samples collection: a. Proportion of children with samples collected as per protocol b. Turnaround time between NPA or stool sample collection and result of Ultra 12 weeks
Secondary Outcome 12. In the intervention arm only - Safety of NPA collection: adverse events collected by study nurses during NPA collection such as vomiting, nose bleeding, low oxygen saturation 12 weeks
Secondary Outcome 13. In the intervention arm only - Tolerability of NPA specimen collection procedures assessed by the child: discomfort/pain/distress experienced by the child assessed by the child him/herself (Wong-Baker face scale) real time
Secondary Outcome 14. In the intervention arm only - Tolerability of NPA specimen collection procedures assessed by the parents: Discomfort/pain/distress experienced by the child assessed by the parents (visual analog scale) real time
Secondary Outcome 15. In the intervention arm only - Tolerability of NPA specimen collection procedures assessed by the nurses: discomfort/pain/distress experienced by the child assessed by the nurses (FLACC behavioural scale) real time
Secondary Outcome 16. In the intervention arm only - Acceptability of NPA and stool specimen collection procedures assessed by parents and nurses (semi-structured interviews and auto-questionnaires). real time
Secondary Outcome 17. Incremental cost-effectiveness ratio (ICER) 12 weeks
Secondary Outcome To assess the prevalence of Covid-19 (confirmed and probable cases) in children below 5 years admitted with WHO-defined severe pneumonia 12 weeks
Secondary Outcome Number of inpatients death in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) 12 weeks
Secondary Outcome Duration of initial hospitalization in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) 12 weeks
Secondary Outcome Number of readmissions following discharge in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) 12 weeks
Secondary Outcome Weight gain in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) 12 weeks
Secondary Outcome Inability to breastfeed or drink in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) Hospital admission
Secondary Outcome Inability to breastfeed or drink in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) 3 day after hospitalisation
Secondary Outcome Inability to breastfeed or drink in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) At hospital discharge, estimated average 7 days
Secondary Outcome Lethargy or reduced level of consciousness in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) Hospital admission
Secondary Outcome Lethargy or reduced level of consciousness in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) 3 day after hospitalisation
Secondary Outcome Lethargy or reduced level of consciousness in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) At hospital discharge, estimated average 7 days
Secondary Outcome Convulsions in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) Hospital admission
Secondary Outcome Convulsions in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) 3 day after hospitalisation
Secondary Outcome Convulsions in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) At hospital discharge, estimated average 7 days
Secondary Outcome Stridor in calm child in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) Hospital admission
Secondary Outcome Stridor in calm child in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) 3 day after hospitalisation
Secondary Outcome Stridor in calm child in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) At hospital discharge, estimated average 7 days
Secondary Outcome Oxygen saturation < 90% in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) Hospital admission
Secondary Outcome Oxygen saturation < 90% in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) 3 day after hospitalisation
Secondary Outcome Oxygen saturation < 90% in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) At hospital discharge, estimated average 7 days
Secondary Outcome Central cyanosis in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) Hospital admission
Secondary Outcome Central cyanosis in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) 3 day after hospitalisation
Secondary Outcome Central cyanosis in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) At hospital discharge, estimated average 7 days
Secondary Outcome Grunting in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) Hospital admission
Secondary Outcome Grunting in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) 3 day after hospitalisation
Secondary Outcome Grunting in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) At hospital discharge, estimated average 7 days
Secondary Outcome Nasal flaring in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) Hospital admission
Secondary Outcome Nasal flaring in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) 3 day after hospitalisation
Secondary Outcome Nasal flaring in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) At hospital discharge, estimated average 7 days
Secondary Outcome Chest in-drawing in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) Hospital admission
Secondary Outcome Chest in-drawing in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) 3 day after hospitalisation
Secondary Outcome Chest in-drawing in children with severe pneumonia (infected with SARS-CoV-2 versus to uninfected children) At hospital discharge, estimated average 7 days
Secondary Outcome To describe the laboratory characteristics (CRP) of Covid-19 cases 12 weeks
Secondary Outcome To describe the laboratory characteristics (full blood count) of Covid-19 cases 12 weeks
Secondary Outcome Description by type and frequency of the signs of viral pneumonia on CXR with interstitial changes of Covid-19 cases 12 weeks
Secondary Outcome To assess the yield of stool as compared to nasal swab for the detection of the SARS-CoV-2 by real time reverse transcription‐polymerase chain reaction (RT-PCR) 12 weeks
Secondary Outcome Number of children having a PCR positive for respiratory syncytial virus 12 weeks
Secondary Outcome To assess seroprevalence and seroconversion (immunoglobulin M and immunoglobulin G to SARS-CoV-2) at Day 0 and Month 3 12 weeks
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
National Pediatric Hospital St 122 Phnom Penh Cambodia
Takeo Provincial Referral Hospital Doun Kaev Takeo Cambodia
Kampong Cham Provincial Referral Hospital Ou Reang Ov Kampong Cham Cambodia
Chantal Biya Foundation Rue Henri Dunant Yaounde Cameroon
Biyem Assi District Hospital Rue Cfeier Yaounde Cameroon
Treichville University Teaching Hospital Boulevard de Marseille Abidjan Cote Divoire
Cocody University Teaching Hospital Boulevard de l Universite Abidjan Cote Divoire
Yopougon University Teaching Hospital S 804 Abidjan Cote Divoire
Maputo Central Hospital Avenida Agostinho Neto n164 Maputo Mozambique
Mulago National Referral Hospital Upper Mulago Hill Road Kampala Uganda
Holy Innocents Childrens Hospital To Mwizi and Isingiro Mbarara Uganda
Jinja Regional Reference Hospital Rotary Road Jinja Uganda
Arthur Davidson Children Hospital Boundary Road Ndola Zambia
Lusaka University Teaching Hospital Nationalist Road Lusaka Zambia
Jose Macamo Hospital 1033 Avenida Oua Maputo Mozambique
Angr UTH BP 54378 Abidjan Cote Divoire
FUNDING SOURCES
Name of source Street address City Postal code Country
Unitaid 1218 Le Grand-Saconnex Geneva Switzerland
5 percent Initiative 73 Rue de Vaugirard Paris France
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 Organization
COLLABORATORS
Name Street address City Postal code Country
Laurence Borand Pasteur Institute in Cambodia Phnom Penh Cambodia
Mao Tan Eang National Center for Tuberculosis Phnom Penh Cambodia
Jean Voisin Taguebue Chantal Biya Foundation Yaounde Cameroon
Raoul Moh Programme PACCI Abidjan Cote Divoire
Laurence Adonis Koffi Service de Pediatrie CHU de Yopougon Abidjan Cote Divoire
Celso Khosa Instituto Nacional de Saude Maputo Mozambique
Sandra Mavale Paediatrics Department Maputo Central Hospital Maputo Mozambique
Juliet Mwanga Amumpere Epicentre Mbarara Research Centre Mbarara Uganda
Chishala CHABALA University of Zambia School of Medicine Lusaka Zambia
Veronica Mulenga Childrens Hospital University Teaching Hospital Lusaka Zambia
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Olivier Marcy olivier.marcy@u-bordeaux.fr +33557574723 Inserm U1219 146 rue Leo Saignat
City Postal code Country Position/Affiliation
Bordeaux France Coordinating Investigator University of Bordeaux
Role Name Email Phone Street address
Public Enquiries Emmanuelle Baillet emmanuelle.baillet@u-bordeaux.fr +33557574718 Inserm U1219 146 rue Leo Saignat
City Postal code Country Position/Affiliation
Bordeaux France Communications Officer University of Bordeaux
Role Name Email Phone Street address
Scientific Enquiries Aurelia Vessiere aurelia.vessiere@u-bordeaux.fr +33557571535 Inserm U1219 146 rue Leo Saignat
City Postal code Country Position/Affiliation
Bordeaux France International Trial Manager University of Bordeaux
Role Name Email Phone Street address
Principal Investigator Maryline Bonnet maryline.bonnet@ird.fr +256793328744 IRD UMI233 911 Avenue Agropolis
City Postal code Country Position/Affiliation
Montpellier France Coordinating Investigator IRD
Role Name Email Phone Street address
Principal Investigator Eric Wobudeya ewobudeya@mujhu.org +256712846163 MUJHU Care Ltd Upper Mulago Hill Road
City Postal code Country Position/Affiliation
Kampala Uganda Coordinating Investigator MUJHU Care Ltd
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 theTB-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