Evidence map›Paper›PMID 30397355›Full record

Trial reportNature medicine2018

A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis.

Marjorie Z Imperial, Payam Nahid, Patrick P J Phillips, Geraint R Davies, Katherine Fielding, Debra Hanna, David Hermann, Robert S Wallis, John L Johnson, Christian Lienhardt and 1 more

Erratum issued Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03941496 (Phase 1b/2a Safety and Immunogenicity of the DNMT Inhibitor Azacitidine During Anti-Tuberculosis Therapy), which is not on this map. Cited by 214 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
214citing papers in PubMed, 13 pooled it
21.7field-weighted citation impact, top 1% 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.

NCT03941496 phase1 / phase2withdrawnnot on this mapstarted 2022, after this paper: background citation

Phase 1b/2a Safety and Immunogenicity of the DNMT Inhibitor Azacitidine During Anti-Tuberculosis Therapy

TypeinterventionalSponsorAndrew DinardoRan2022 to 2023Enrolled0ConditionsTuberculosis, PulmonaryArmsAzacitidine Injection
3 · Its place in the literature

Who cites it

214 citing papers in PubMed, 13 syntheses or guidelines pooled it, 365 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Subclinical tuberculosis: a meta-analysis of prevalence and scoping review of definitions, prevalence and clinical characteristics.European respiratory review : an official journal of the European Respiratory Society · 2024
    Pooled it
  7. Pooled it
  8. Effectiveness and Pharmacokinetic Exposures of First-Line Drugs Used to Treat Drug-Susceptible Tuberculosis in Children: A Systematic Review and Meta-Analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
    Pooled it
  9. Pooled it
  10. Pooled it
  11. Pooled it
  12. Pooled it
  13. Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.American journal of respiratory and critical care medicine · 2019
    Guideline
  14. Trial
  15. Trial
  16. Trial
  17. Trial
  18. Pharmacokinetic-Pharmacodynamic Evidence From a Phase 3 Trial to Support Flat-Dosing of Rifampicin for Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024
    Trial
  19. Trial
  20. Trial

154 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 7 institutions in 5 countries.

Marjorie Z ImperialUniversity of California, San Francisco, San Francisco, CA, USA.
Payam NahidUniversity of California, San Francisco, San Francisco, CA, USA.
Patrick P J PhillipsUniversity of California, San Francisco, San Francisco, CA, USA.
Geraint R DaviesUniversity of Liverpool, Liverpool, UK.
Katherine FieldingLondon School of Hygiene and Tropical Medicine, London, UK.
Debra HannaCritical Path Institute, Tucson, AZ, USA.
David HermannBill and Melinda Gates Foundation, Seattle, WA, USA.
Robert S WallisAurum Institute and ACT4TB/HIV, Johannesburg, South Africa.
John L JohnsonCase Western Reserve University, Cleveland, OH, USA.
Christian LienhardtGlobal Tuberculosis Programme, World Health Organization, Geneva, Switzerland.
Rada M SavicUniversity of California, San Francisco, San Francisco, CA, USA. rada.savic@ucsf.edu.ORCID http://orcid.org/0000-0003-3143-5579
University of California, San Francisco · USGates Foundation · USAurum Institute · ZAInserm · FRLondon School of Hygiene & Tropical Medicine · GBUniversity Hospitals of Cleveland · USUniversity of Liverpool · GB

Funding

PHARMACEUTICAL SCIENCES AND PHARMACOGENOMICST32GM007175 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, KROETZ, DEANNA L · 1985 to 2021
$7.1M
Sputum Transcriptomic Expression Profiling in Study 31: Express 31R01AI127300 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DAVIS, JOHN LUCIAN, NAHID, PAYAM · 2017 to 2022
$6.2M
TB Surrogate Markers for Assessing Reponse to Treatment (TB SMART Study)R01AI104589 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NAHID, PAYAM, SIGAL, GEORGE B · 2013 to 2017
$6.2M
Tuberculosis Prevention Research Unit /TBRU/-266095383N01AI095383 · NIAID · CASE WESTERN RESERVE UNIVERSITY · 2000 to 2005
$5.6M
Medical Research Council MR/K012126/1NIAID NIH HHS N01 AI070022NIAID NIH HHS N01 AI095383NIAID NIH HHS R01 AI104589NIAID NIH HHS R01 AI127300NIGMS NIH HHS T32 GM007175World Health Organization 001
6 · The paper itself

Abstract

Tuberculosis kills more people than any other infectious disease. Three pivotal trials testing 4-month regimens failed to meet non-inferiority margins; however, approximately four-fifths of participants were cured. Through a pooled analysis of patient-level data with external validation, we identify populations eligible for 4-month treatment, define phenotypes that are hard to treat and evaluate the impact of adherence and dosing strategy on outcomes. In 3,405 participants included in analyses, baseline smear grade of 3+ relative to <2+, HIV seropositivity and adherence of ≤90% were significant risk factors for unfavorable outcome. Four-month regimens were non-inferior in participants with minimal disease defined by <2+ sputum smear grade or non-cavitary disease. A hard-to-treat phenotype, defined by high smear grades and cavitation, may require durations >6 months to cure all. Regimen duration can be selected in order to improve outcomes, providing a stratified medicine approach as an alternative to the 'one-size-fits-all' treatment currently used worldwide.

Indexed as

Antitubercular AgentsDose-Response Relationship, DrugFemaleHumansKaplan-Meier EstimateMaleMiddle AgedPhenotypeRisk FactorsSputumTreatment OutcomeTuberculosis, Multidrug-ResistantTuberculosis, PulmonaryAntitubercular Agents

Identifiers

PMID30397355
PMCPMC6685538
OpenAlexW2895784427

What OpenQuestion holds

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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.