Tuberculosis

endTB aims to find shorter, less toxic and more effective treatments for 'multidrug-resistant TB' (MDR-TB). In this randomized, controlled, open-label, multi-country Phase III trial, 5 experimental regimens containing 1 or 2 new drugs in patients with fluoroquinolone-susceptible MDR-TB are trailed. The objective is to assess whether the efficacy of experimental regimens at Week 73 is non-inferior to that of the control.

Countries

Georgia, India, Kazakhstan, Lesotho, Pakistan, Peru, South Africa, Vietnam

Tentative End date

April 2023

Our Role

Statistics & Data Management

For more information contact: Maelenn Gouillou

ENDTB-Q is a randomized, controlled, open-label, multi-country Phase III trial (Randomization (2:1 in favor of the experimental arm) is stratified by country and extent-of-TB-disease phenotype). The objective is to Identify an effective, shorter, less toxic and injection-free regimen for FQ-resistant MDR-TB as compared to the current standard of care. The primary objective is to assess whether the efficacy of experimental 6 to 9 months regimen is non-inferior to that of the control at 73 weeks.

Countries

India, Kazakhstan, Lesotho, Pakistan, Peru, Vietnam

Tentative End date

April 2023

Our Role

Statistics & Data Management

For more information contact: Maelenn Gouillou

PandrTB is a study of the pharmacokinetics (PK) and pharmacodynamics (PD) of bedaquiline, delamanid, clofazimine, linezolid, moxifloxacin, levofloxacin and pyrazinamide used in novel combinations to treat rifampicinresistant tuberculosis (RR-TB), including multidrug-resistant TB (MDR-TB), and fluoroquinolone-resistant TB (QR-TB). PandrTB is an observational study nested in the endTB and endTB-Q trials. The overarching aim is to estimate the PK and PD of the drugs as used in combination across the experimental arms of the endTB and endTB-Q trials.

Countries

Lesotho, Peru, South Africa, Pakistan

Tentative End date

April 2023

Our Role

Statistics & Data Management

For more information contact: Maelenn Gouillou

For people with HIV associated severe immune suppression (CD4 ≤ 100 cells/ μL), TB incidence is high and represents the most frequent cause of hospitalization and death. In this study, "Determination of Adequate Tuberculosis Regimen in Adults and adolescents hospitalised with HIV associated severe immune suppression (CD4 ≤ 100 cells/μL)", we hypothesize that intensification of the initial phase of TB treatment, by increasing doses of two major TB drugs, rifampicin and isoniazid, and adding systematic corticosteroids, will decrease mortality in severely immunosuppressed HIVinfected adults and adolescents hospitalized for TB in comparison with the current standard TB regimen.

Objective

To estimate the impact of an intensified initial phase of Tuberculosis (TB) treatment on mortality at 48 weeks among HIVinfected adults and adolescents hospitalised for TB with CD4 ≤ 100 cells/μL in comparison with the standard TB regimen.

Methodology

A Phase III multicenter, two-arms, open-label randomised controlled superiority trial. Eligible subjects will be randomised in a 1:1 ratio for a total of 665 patients per trial arm, with stratification by country and by CD4 cell counts (≤ 50 or > 50 cells/μL).

Who's Involved Besides MSF?

Inserm - ANRS, EDCTP, Pathogenesis and Control of Chronic Infections (PCCI), UMR1058 (Inserm, University of Montpellier, EFS), Cambodia, Cameroon, Guinea, Uganda, Vietnam, Zambia

Country

Uganda

Tentative End date

December 2024

Our Role

Study Site

For more information contact: Gino Agbota

In 2017, an estimated 10M new cases and 1.6M deaths occurred due to tuberculosis (TB). Despite progress in reducing TB incidence and mortality in the past 20 years, TB is a top ten cause of death in children under 5 years worldwide, with 1,2M new cases and 230’000 deaths in 2019. The vast majority of children dying from TB are children (<5 years old) not accessing treatment, most likely because they are not diagnosed. The TB-Speed project will carry out research activities aiming at reducing childhood mortality.

Country

Uganda

Who's Invovled?

INSERM ; UNITAID ; Université de Bordeaux ; TB-Speed consotrium 

TB-Speed HIV

A prospective multicentre study evaluating the safety & feasibility of the PAANTHER TB treatment decision algorithm for HIV-infected children with presumptive TB, conducted in 4 countries. The objective is to evaluate the safety of withholding TB treatment in HIV-infected children with presumptive TB not initiated on treatment as per the PAANTHER TB treatment-decision algorithm.

Tentative End date

December 2022

Our Role

Study Site

TB-Speed Pneumonia

A multicentric, cluster-randomised pragmatic diagnostic trial conducted in 5 countries, designed as a stepped wedge trial. The objective is to evaluate the impact on all-cause mortality at 12 weeks post inclusion of adding systematic early detection of TB with Ultra to the WHO-SOC in young children with severe pneumonia, followed by immediate anti-TB treatment initiation in children with a positive Ultra result, as compared to the SOC alone.

Tentative End date

December 2022

Our Role

Study Site

TB-Speed Decentralization

An observation phase followed by an intervention phase (randomisation of 2 districts per country between the 2 decentralization strategies). The objective is to assess the impact of a TB diagnostic approach decentralized at district hospital (DH) and Primary Health Care (PHC) levels on childhood TB case detection compared to the pre-intervention status and between 2 decentralized diagnostic strategies at DH and PHC levels.

Tentative End date

December 2022

Our Role

Study Site

TB-Speed Stool Processing

A diagnostic study evaluating the diagnostic accuracy of the Ultra assay in stools with a 2-stage sequential design starting as a cohort of children with presumptive TB enriched in a 2nd stage with Ultra positive TB cases on respiratory samples. The objective is to determine diagnostic accuracy of Xpert Ultra performed on stools processed using 4 different sample processing methods in children with presumptive TB.

Tentative End date

December 2022

Our Role

Study Site

The most lethal and disabling form of TB is TB meningitis (TBM), with an estimated 100,000 new cases occurring per year, representing around 6% of extra-pulmonary TB cases. In sub-saharan Africa, TBM mortality reaches 40% in HIV-negative patients and up to 70% in HIV-positive individuals with drug resistant M. tuberculosis (M. tb) strains. TBM treatment has remained unchanged for decades despite its relatively poor efficacy and there is not enough evidence that new anti-TB drugs becoming available could help manage TBM. In this study, "Intensified TB treatment with or without aspirin to reduce the mortality of HIVinfected and HIV-uninfected patients with tuberculous meningitis" we propose a treatment intensification of the first two months of anti-TB treatment based on high dose rifampicin (35 mg/kg/d orally) and Linézolide (4 weeks at 1200 mg/d and 4 weeks at 600mg/d), added to isoniazid, pyrazinamide and ethambutol at standard doses. The benefit of adding aspirin (200 mg/d) during the induction phase will be evaluated with and without intensified TB treatment. In addition, the study will allow us to gather data on the pharmacological interactions between high dose rifampicin and the new first line antiretroviral dolutegravir, and finally, on the incidence and risk factors of neurologic TB Immune Reconstitution Inflammatory syndrome.

Objective

Assess the efficacy of 2 interventions to reduce mortality from TBM with or without HIV coinfection in sub-Saharan Africa: Intensified TBM treatment compared to WHO standard TBM treatment ; Aspirin compared placebo.

Methodology

This is a randomized controlled, phase III, multicenter, 2 x 2 factorial plan superiority trial. The trial will be open-label for anti-TB treatment and placebo-controlled double blind for aspirin treatment.

Who’s Involved besides MSF?

Inserm-ANRS, EDCTP, MUST Uganda, Mbarara Regional Reference Hospital, Kabale Regional Referal Hospital, Intense TBM consortium:https://intense-tbm.org/

Country

Uganda

Tentative End date

December 2023

Our Role

Study Site

The many gaps observed in the cascade of care of TB child contacts occur mostly in the screening, Preventive Therapy (PT) initiation & completion steps. Household or community-based screening is likely to improve the uptake and acceptability of child contact screening & management as well as adherence to PT and to reduce cost & workload at facility level. In the study "Community Intervention for Tuberculosis Active Contact Tracing and Preventive Therapy - a cluster randomized study (CAP-TB/contact)", we propose a pragmatic international cluster randomized study to compare the cascade of care between two models

1. Community based with screening of contacts, decentralized initiation and follow-up of PT in the community by a trained community health worker ;
2. Facility based for initiation and follow-up of PT) for TB screening and management of household TB child contacts in high TB burden and limited resource countries. In both models, symptomatic children requiring further investigations for TB diagnosis will be referred to a health facility.

Objective

To compare the proportion of household child TB contacts eligible for PT who initiate and complete PT using facility-based and decentralized communitybased models of care for contact screening and management.

Methodology

International cluster randomized study. 20 clusters in Cameroon and Uganda were allocated to either the community-based or facility based intervention for household child screening and PT management.

Who's Involved Besides MSF?

EGPAF, UNITAID, IRD

Country

Uganda

Tentative End date

December 2022

Our Role

Study Site

The current treatment of tuberculosis (TB) involves taking drugs daily for 6 or 8 months. Although the drugs are free to patients in low-income countries, this still involves costs in terms of time and administration to both patients & treatment services. If the treatment could be shortened to 3, or even, 4 months, this could result in greater cure rates and, perhaps, a reduction in the emergence of resistance to the drugs. Rifampicin is one of the drugs given in treatment, and laboratory experiments suggest that increasing the dose of rifampicin results in a greater and faster killing of the tubercle bacillus. This trial is an open-label 3-arm trial to compare a standard 6-month control regimen with two 4-month treatment regimens for the treatment of TB. Patients enrolled in the trial are randomly allocated to receive one of the 3 chemotherapy regimens: standard dose (10mg/kg body weight at start of treatment); study regimen 1 (1200mg) or study regimen 2 (1800mg daily). The objective is to determine whether:

1. an increase in the daily dose of rifampicin from the current WHO recommended dose would result in more rapid sterilisation of the lungs and allow a reduction of treatment duration to 4 months; (
2. the increased doses do not result in an increase in severe or serious adverse events.

Country

Uganda

Tentative End date

December 2022

Our Role

Study Site

RIFASHORT PERSISTER STUDY

Persisters are a subpopulation of bacteria that remain viable after the initial killing action of antibiotics. This persister substudy is nested in the Rifashort trial. Sputum samples are collected at different timepoints during the early phase of treatment. The specific bacterials sub-populations in patients' sputum are quantified. The objective is to investigate the predictive value for cure of quantifying specific bacterial subpopulations in patients' sputum during the early phase of treatment for TB.

Country

Uganda

Tentative End date

December 2022

Our Role

Study Site

For more information contact: Daniel  Atwine

Diagnostic performance of a novel lipoarabinomannan test (FujiLAM) to detect tuberculosis in HIV-positive patients

Tuberculosis (TB) is the leading cause of death in HIV-positive individuals. Underdiagnosis of TB is a principal barrier to combatting the disease. In resource-limited settings, molecular diagnoses such as Xpert MTB/RIF are still not widely available and sputum samples can be difficult to produce, especially for very ill HIV-positive patients.

The Fujifilm SILVAMP TB LAM (FujiLAM; Fujifilm, Tokyo, Japan) is a novel (not commercialised) urine- based point-of-care assay to diagnose TB in HIV-positive patients. A first study using urine frozen samples has reported a higher sensitivity of this test over the currently commercialised Alere Determine TB LAM Ag assay (AlereLAM).

The aim of this study is to investigate the diagnostic performance of FujiLAM in ambulatory HIV- positive patients from fresh urine samples.

Primary objective: To assess the sensitivity of FujiLAM among patients with microbiological confirmed TB in two groups of HIV-positive patients: 1) ambulatory adult HIV-positive patients with signs and symptoms of TB regardless of their CD4 count (Group 1), and 2) ambulatory adult patients with advanced HIV disease and no signs and symptoms of TB (Group 2).

Secondary objectives: To assess the sensitivity of FujiLAM and AlereLAM in urine by level of CD4 among patients with microbiologically confirmed TB and among patients with probable TB or microbiologically confirmed TB, the diagnostic performance of algorithms including FujiLAM, the mortality at 6 months according to the FujiLAM result and the feasibility of using the FujiLAM at point-of-care and the test acceptability by test users, clinic managers and patients.

Country

South Africa, Kenya, Mozambique, Uganda

Tentative End date

December 2022

Our Role

Coordination

Who's Involved

• OCP, OCG, OCB
• Mbarara University of Science and Technology (MUST)
• Ministry of Health Uganda
• Ministry of Health Kenya
• Ministry of Health Mozambique
• Ministry of Health South Africa
• ANRS