Impact of Systematic Early Tuberculosis Detection Using Xpert MTB/RIF Ultra in Children With Severe Pneumonia in High Tuberculosis Burden Countries (TB-Speed Pneumonia)

NCT03831906 | Completed DMC

• 1 other identifier: C18-26
• Study Type: interventional
• Target: 2,570
• Locations: 5 countries
• Sites: 13

Brief Summary

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 World Health Organization (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-CoV-2 infection status in the main study analysis.

Conditions

Tuberculosis; Severe Pneumonia; Covid19

Outcome Measures

Primary Outcomes (1)

• All-cause mortality 12 weeks after inclusion

  12 weeks

Secondary Outcomes (55)

• Number of children diagnosed with TB at 12 weeks

  12 weeks

• • Proportion of children with TB treatment initiated at any time during follow-up

  12 weeks

• • Time to TB treatment initiation

  12 weeks

• • Duration of TB treatment at end of trial

  12 weeks

• • Number of inpatient deaths

  12 weeks

Other Outcomes (1)

• Comparison of the cost-effectiveness of the two strategies

  12 weeks

Study Arms (2)

Control

NO INTERVENTION

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).

Interventional

EXPERIMENTAL

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.

Diagnostic Test: Xpert MTB/RIF Ultra (Ultra)

Interventions

Xpert MTB/RIF Ultra (Ultra) DIAGNOSTIC_TEST

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.

Interventional

Eligibility Criteria

• Age: 2 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children aged 2 to 59 months
• Newly hospitalized for severe pneumonia defined using WHO criteria as cough or difficulty in breathing with:
• Peripheral oxygen saturation \< 90% or central cyanosis, or
• Severe respiratory distress (e.g. grunting, nasal flaring, very severe chest indrawing), or
• Signs of pneumonia, defined as cough or difficulty in breathing with fast breathing (tachypnea) and/or chest indrawing, with any of the following danger signs:
• Inability to breastfeed or drink,
• Persistent vomiting
• Lethargy or reduced level of consciousness
• Convulsions,
• Stridor in calm child
• Severe malnutrition
• Informed consent signed by parent/guardian

You may not qualify if:

• \- Ongoing TB treatment or history of intake of anti-TB drugs in the last 6 months

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• UNITAID: collaborator

Study Sites (16)

Kampong Cham Provincial Referral Hospital

Kampong Cham, Cambodia

Location

National Pediatric Hospital

Phnom Penh, Cambodia

Location

Takeo Provincial Referral Hospital

Takeo, Cambodia

Location

Biyem Assi District Hospital

Yaoundé, Cameroon

Location

Chantal Biya Foundation

Yaoundé, Cameroon

Location

Angré University Teaching Hospital

Abidjan, Côte d’Ivoire

Location

Cocody University Teaching Hospital

Abidjan, Côte d’Ivoire

Location

Treichville University Teaching Hospital

Abidjan, Côte d’Ivoire

Location

Yopougon University Teaching Hospital

Abidjan, Côte d’Ivoire

Location

José Macamo General Hospital

Maputo, Mozambique

Location

Maputo Central Hospital

Maputo, Mozambique

Location

Jinja Regional Reference Hospital

Jinja, Uganda

Location

Mulago National Referral Hospital

Kampala, Uganda

Location

Holy Innocents Children's Hospital

Mbarara, Uganda

Location

Lusaka University Teaching Hospital

Lusaka, Zambia

Location

Arthur Davidson Children Hospital

Ndola, Zambia

Location

Related Publications (3)

• Vessiere A, Font H, Gabillard D, Adonis-Koffi L, Borand L, Chabala C, Khosa C, Mavale S, Moh R, Mulenga V, Mwanga-Amumpere J, Taguebue JV, Eang MT, Delacourt C, Seddon JA, Lounnas M, Godreuil S, Wobudeya E, Bonnet M, Marcy O. Impact of systematic early tuberculosis detection using Xpert MTB/RIF Ultra in children with severe pneumonia in high tuberculosis burden countries (TB-Speed pneumonia): a stepped wedge cluster randomized trial. BMC Pediatr. 2021 Mar 20;21(1):136. doi: 10.1186/s12887-021-02576-5.

  PMID: 33743621 RESULT

• Marcy O, Wobudeya E, Font H, Vessiere A, Chabala C, Khosa C, Taguebue JV, Moh R, Mwanga-Amumpaire J, Lounnas M, Mulenga V, Mavale S, Chilundo J, Rego D, Nduna B, Shankalala P, Chirwa U, De Lauzanne A, Dim B, Tiogouo Ngouana E, Folquet Amorrissani M, Cisse L, Amon Tanoh Dick F, Komena EA, Kwedi Nolna S, Businge G, Natukunda N, Cumbe S, Mbekeka P, Kim A, Kheang C, Pol S, Maleche-Obimbo E, Seddon JA, Mao TE, Graham SM, Delacourt C, Borand L, Bonnet M; TB-Speed Pneumonia Study Group. Effect of systematic tuberculosis detection on mortality in young children with severe pneumonia in countries with high incidence of tuberculosis: a stepped-wedge cluster-randomised trial. Lancet Infect Dis. 2023 Mar;23(3):341-351. doi: 10.1016/S1473-3099(22)00668-5. Epub 2022 Nov 14.

  PMID: 36395782 DERIVED

• Kay AW, Gonzalez Fernandez L, Takwoingi Y, Eisenhut M, Detjen AK, Steingart KR, Mandalakas AM. Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for active tuberculosis and rifampicin resistance in children. Cochrane Database Syst Rev. 2020 Aug 27;8(8):CD013359. doi: 10.1002/14651858.CD013359.pub2.

  PMID: 32853411 DERIVED

Related Links

• TB-Speed project official website

MeSH Terms

Conditions

Tuberculosis; Pneumonia; COVID-19

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Study Officials

• Olivier Marcy, MD, PhD

  University of Bordeaux, France

  PRINCIPAL INVESTIGATOR

• Maryline Bonnet, MD, PhD

  Institut de Recherche pour le Développemnt (IRD) Montpellier, France

  PRINCIPAL INVESTIGATOR

• Eric Wobudeya, MD, PhD

  MU-JHU Care Ltd, Kampala, Uganda

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: The TB-Speed Pneumonia study is a stepped wedge cluster-randomised trial. Clusters, i.e.hospitals, will successively switch from control to intervention in an order randomly assigned, until all clusters are eventually exposed to the intervention. The TB-Speed Pneumonia study will be implemented in 15 hospitals. At the start of the study, all hospital will be implementing the WHO SOC for severe pneumonia (control arm). One hospital will then switch to the TB-Speed strategy (intervention arm) every 5 weeks. Randomisation will be stratified on the country estimated TB incidence rate (see Table 3): \<300/100,000 patients-years (Cameroon, Cote d'Ivoire and Uganda) vs. ≥300/100,000 patients-years (Cambodia, Mozambique and Zambia).

Study Record Dates

• First Submitted: February 1, 2019
• First Posted: February 6, 2019
• Study Start: March 20, 2019
• Primary Completion: June 30, 2021
• Study Completion: June 30, 2021
• Last Updated: December 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

UG (3); CÔ (4); MO (2); ZA (2); CA (2)