Evidence map›Paper›PMID 42270675›Full record

Trial reportNature communications2026

Pharmacokinetics, bactericidal activity and toxicity of short oral regimens for rifampicin-resistant tuberculosis treatment.

Bern-Thomas Nyang'wa, Ilaria Motta, Ronelle Moodliar, Varvara Solodovnikova, Shakira Rajaram, Mohammed Rasool, Catherine Berry, David A J Moore, Geraint Davies, Frank Kloprogge

Registry-linked trialAbstract readClinical Trial, Phase IIClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04081077 (Pharmacokinetics and Pharmacodynamics Sub-study for TB-PRACTECAL Clinical Trial), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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.

NCT04081077 phase2 / phase3unknown statusnot on this map

Pharmacokinetics and Pharmacodynamics Sub-study for TB-PRACTECAL Clinical Trial ( PRACTECAL-PKPD)

TypeinterventionalSponsorMedecins Sans Frontieres, NetherlandsRan2019 to 2022Enrolled240ConditionsMulti-drug Resistant Tuberculosis, Extensively Drug-Resistant Tuberculosis, Pulmonary TuberculosisArmsBedaquiline, Pretomanid, Moxifloxacin, Linezolid, Clofazimine
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
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

10 authors.

Bern-Thomas Nyang'waMédecins sans Frontieres, Public Health Department, Amsterdam, The Netherlands. bern.nyangwa@london.msf.org.ORCID http://orcid.org/0000-0001-9915-5878
Ilaria MottaUniversity College London, Innovative Clinical Trials Unit, London, United Kingdom.
Ronelle MoodliarTHINK (TB & HIV Investigative Network) Durban, Durban, South Africa.
Varvara SolodovnikovaRepublican Scientific and Practical Centre of Pulmonology and Tuberculosis, Minsk, Belarus.
Shakira RajaramClinical HIV Research Unit (CHRU), Wits Health Consortium (WHC), Department of Internal Medicine, School of Clinical medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
Mohammed RasoolClinical HIV Research Unit (CHRU), Wits Health Consortium (WHC), Department of Internal Medicine, School of Clinical medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
Catherine BerryMédecins sans Frontieres, Manson Unit, Public Health Department, London, United Kingdom.ORCID http://orcid.org/0000-0001-6363-9387
David A J MooreLondon School of Hygiene and Tropical Medicine, Clinical Research Department, London, United Kingdom.ORCID http://orcid.org/0000-0002-3748-0154
Geraint DaviesUniversity of Liverpool, Department of Clinical Infection, Microbiology and Immunology, Liverpool, United Kingdom.
Frank KloproggeInstitute for Global Health, University College London, London, United Kingdom. f.kloprogge@ucl.ac.uk.ORCID http://orcid.org/0000-0001-7213-4559

Funding

Wellcome TrustWellcome Trust (Wellcome) 220587/Z/20/Z
6 · The paper itself

Abstract

The exposure and both Mycobacterium tuberculosis clearance rates and toxicity relationships of bedaquiline-pretomanid-linezolid- (BPaL), BPaL-clofazimine (BPaLC) and BPaL-moxifloxacin (BPaLM) for treatment of rifampicin-resistant tuberculosis remain understudied. Therefore, the relationship between the patients' exposure to anti-TB drugs in TB-PRACTECAL trial investigational regimens and their treatment outcomes was investigated. PRACTECAL-PKPD was a prospective pharmacokinetics and pharmacodynamics study. Patients with rifampicin-resistant tuberculosis were enrolled from Belarus and South Africa. Antimicrobial exposures for bedaquiline, pretomanid, linezolid, moxifloxacin and clofazimine were adequately estimated, were within the ranges of previously published studies but did not correlate with the speed of sputum bacterial clearance. When compared to the standard of care (SoC) arm, a 20% increased bacillary killing rate with BPaLM was observed, whilst BPaL and BPaLC displayed a 15% decreased rate. Also of note was a 20% decreased bacillary killing rate in patients with severe disease irrespective of treatment. Linezolid exposure was higher amongst patients with anaemia or neutropenia. No other exposure-toxicity relationships were identified for all other drugs. These data indicate that the studied doses of linezolid and moxifloxacin could be the right balance between effectiveness and safety, strengthening the WHO recommendation that BPaLM is the preferred regimen for rifampicin-resistant tuberculosis in adolescents and adults. The study was registered in Clinical Trials.gov, TRN: NCT04081077.

Indexed as

Antitubercular AgentsMycobacterium tuberculosisRifampinTuberculosis, Multidrug-ResistantAdministration, OralAdultClofazimineDiarylquinolinesFemaleHumansLinezolidMaleMicrobial Sensitivity TestsMiddle AgedMoxifloxacinNitroimidazolesAntitubercular AgentsbedaquilineClofazimineDiarylquinolinesLinezolidMoxifloxacinNitroimidazolespretomanidRifampin

Identifiers

PMID42270675
PMCPMC13439552

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.