Evidence map›Paper›PMID 38037119›Full record

ArticleTrials2023

Evaluating newly approved drugs in combination regimens for multidrug-resistant tuberculosis with fluoroquinolone resistance (endTB-Q): study protocol for a multi-country randomized controlled trial.

S B Patil, M Tamirat, K Khazhidinov, E Ardizzoni, M Atger, A Austin, E Baudin, M Bekhit, S Bektasov, E Berikova and 43 more

Registry-linked trialOpen access · goldAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Trials, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03896685 (Evaluating Newly Approved Drugs in Combination Regimens for Multidrug-Resistant TB With Fluoroquinolone Resistance), which is not on this map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.1field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03896685 phase3completednot on this map

Evaluating Newly Approved Drugs in Combination Regimens for Multidrug-Resistant TB With Fluoroquinolone Resistance (endTB-Q)

TypeinterventionalSponsorMédecins Sans Frontières, FranceRan2020 to 2024Enrolled323ConditionsTuberculosis, Multidrug-Resistant, Tuberculosis, Pulmonary Tuberculoses, Mycobacterial InfectionsArmsBedaquiline 100 MG, Delamanid 50 MG Oral Tablet, Clofazimine 100 MG Oral Capsule, Linezolid 600Mg Tab, Control arm MDR-TB regimen, designed according to latest WHO guidelines
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 11 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

53 authors at 20 institutions in 10 countries.

S B Patil *Indian Council of Medical Research (ICMR) - National AIDS Research Institute, Pune, India.
M Tamirat *Partners In Health, Maseru, Lesotho.
K Khazhidinov *Partners In Health, Astana, Kazakhstan.
E ArdizzoniInstitute of Tropical Medicine (ITM), Antwerp, Belgium.
M AtgerMedical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France.
A AustinUCSF Center for Tuberculosis, University of California, , San Francisco, San Francisco, CA, USA.
E BaudinEpicentre, Paris, France.
M BekhitMedical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France.
S BektasovNational TB Center, Almaty, Kazakhstan.
E BerikovaPartners In Health, Astana, Kazakhstan.
M BonnetUniversité de Montpellier, IRD, INSERM, Montpellier, TransVIHMI, France.
R CabocloMedical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France.
M ChaudhryMedical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France.
V ChavanMédecins Sans Frontières, Mumbai, India.
S CloezMedical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France.
J CoitDepartment of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.
S CoutissonMédecins Sans Frontières, Geneva, Switzerland.
Z DakenovaCity Center of Phthisiopulmonology, Astana, Kazakhstan.
B C De JongInstitute of Tropical Medicine (ITM), Antwerp, Belgium.
C DeliferMedical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France.
S DemaisonsMedical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France.
J M DoDepartment of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.
D Dos Santos TozziIncyte, Morges, Switzerland.
V DucherMedical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France.
G FerlazzoMédecins Sans Frontières, Geneva, Switzerland.
M GouillouEpicentre, Paris, France.
U KhanInteractive Research and Development (IRD) Global, Singapore, Singapore.
M KundaPartners In Health, Maseru, Lesotho.
N LachenalMédecins Sans Frontières, Geneva, Switzerland.
A N LaHoodDepartment of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.
L LeccaDepartment of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.
M MazmanianMedical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France.
H McIlleronDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
M MoreauMedical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France.
M MoschioniMedicines Patent Pool, Geneva, Switzerland.
P NahidUCSF Center for Tuberculosis, University of California, , San Francisco, San Francisco, CA, USA.
E OssoDepartment of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.
L OyewusiPartners In Health, Maseru, Lesotho.
S PandaIndian Council of Medical Research Headquarters, New Delhi, India.
A PâquetMedical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France.
P Thuong HuuHanoi Lung Hospital, Hanoi, Vietnam.
L PichonMedical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France.
M L RichPartners In Health, Boston, MA, USA.
P RupasingheInstitute of Tropical Medicine (ITM), Antwerp, Belgium.
N SalahuddinIndus Hospital & Health Network, Karachi, Pakistan.
E Sanchez GaravitoHospital Nacional Sergio E. Bernales, Lima, Peru.
K J SeungPartners In Health, Boston, MA, USA.
G E VelásquezUCSF Center for Tuberculosis, University of California, , San Francisco, San Francisco, CA, USA.
M ValletMedical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France.
F VaraineMedical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France.
F J Yuya-SeptohEpicentre, Paris, France.
C D Mitnick *Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.
L Guglielmetti *Medical Department, Médecins Sans Frontières, 14-34 Avenue Jean Jaurès, 75019, Paris, France. Lorenzo.GUGLIELMETTI@paris.msf.org.
Médecins Sans Frontières · FRPartners In Health · USHarvard Global Health Institute · USInstituut voor Tropische Geneeskunde · BEMédecins Sans Frontières · CHUniversity of California, San Francisco · USHarvard University · USBrigham and Women's Hospital · USCentre d'Immunologie et des Maladies Infectieuses · FREsSALUD · PEHanoi Lung Hospital · VNIndian Council of Medical Research · INIndus Hospital · PKKazakh Institute of Oncology and Radiology · KZMedicines Patent Pool · CHNational AIDS Research Institute · INNational Nuclear Center of the Republic of Kazakhstan · KZSorbonne Université · FRUniversidad Privada Sergio Bernales · PEUniversité de Montpellier · FR

Funding

Unitaid SPHQ15-LOA-045
6 · The paper itself

Abstract

backgroundTreatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients.

methodsendTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations. DISCUSSION: This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen.

trial registrationClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023.

Indexed as

Extensively Drug-Resistant TuberculosisTuberculosis, Multidrug-ResistantAntitubercular AgentsClinical Trials, Phase III as TopicClofazimineFluoroquinolonesHumansLinezolidNitroimidazolesOxazolesRandomized Controlled Trials as TopicAntitubercular AgentsClofazimineFluoroquinolonesLinezolidNitroimidazolesOPC-67683OxazolesBedaquilineClofazimineDelamanidFluroquinolone-resistantLinezolidMDR-TBMultidrug-resistantNon-inferiorityPre-XDR TBRifampicin-resistantRR-TBStratified medicineTreatment shorteningTuberculosis

Identifiers

PMID38037119
PMCPMC10688049
OpenAlexW4389204107

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.