Evidence map›Paper›PMID 38462673›Full record

Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2024

Pharmacokinetic-Pharmacodynamic Evidence From a Phase 3 Trial to Support Flat-Dosing of Rifampicin for Tuberculosis.

Huy X Ngo, Ava Y Xu, Gustavo E Velásquez, Nan Zhang, Vincent K Chang, Ekaterina V Kurbatova, William C Whitworth, Erin Sizemore, Kia Bryant, Wendy Carr and 11 more

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

Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02410772 (Rifapentine-containing Treatment Shortening Regimens for Pulmonary Tuberculosis), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.3field-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.

NCT02410772 phase3completednot on this map

Rifapentine-containing Treatment Shortening Regimens for Pulmonary Tuberculosis: A Randomized, Open-label, Controlled Phase 3 Clinical Trial. TBTC Study 31, ACTG Study A5349

TypeinterventionalSponsorCenters for Disease Control and PreventionRan2016 to 2021Enrolled2,516ConditionsTuberculosisArmsrifapentine, rifapentine and moxifloxacin, control
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. GEODE: anFrontiers in pharmacology · 2025
    Article
  5. Article
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

21 authors at 10 institutions in 3 countries.

Huy X NgoDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
Ava Y XuDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.ORCID 0000-0002-9222-1227
Gustavo E VelásquezUCSF Center for Tuberculosis, University of California, San Francisco, San Francisco, California, USA.
Nan ZhangDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
Vincent K ChangDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
Ekaterina V KurbatovaCenters for Disease Control and Prevention, Atlanta, Georgia, USA.
William C WhitworthCenters for Disease Control and Prevention, Atlanta, Georgia, USA.
Erin SizemoreCenters for Disease Control and Prevention, Atlanta, Georgia, USA.
Kia BryantCenters for Disease Control and Prevention, Atlanta, Georgia, USA.
Wendy CarrCenters for Disease Control and Prevention, Atlanta, Georgia, USA.
Marc WeinerUniversity of Texas Health Science Center at San Antonio and the South Texas Veterans Health Care System, San Antonio, Texas, USA.
Kelly E DooleyDivision of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Melissa EngleUniversity of Texas Health Science Center at San Antonio and the South Texas Veterans Health Care System, San Antonio, Texas, USA.
Susan E DormanMedical University of South Carolina, Charleston, South Carolina, USA.
Payam NahidUCSF Center for Tuberculosis, University of California, San Francisco, San Francisco, California, USA.
Susan SwindellsUniversity of Nebraska Medical Center, Omaha, Nebraska, USA.
Richard E ChaissonJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Pheona NsubugaUganda-Case Western Reserve University Research Collaboration, Kampala, Uganda.
Madeleine LourensTASK Applied Science CRS, Brooklyn Chest Hospital, Bellville, South Africa.
Rodney DawsonDivision of Pulmonology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Radojka M SavicDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
University of California, San Francisco · USCenters for Disease Control and Prevention · USThe University of Texas Health Science Center at San Antonio · USBrooklyn Chest Hospital · ZAJohns Hopkins University · USMedical University of South Carolina · USMUJHU Research Collaboration · UGUniversity of Cape Town · ZAUniversity of Nebraska Medical Center · USVanderbilt University Medical Center · US

Funding

Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
San Francisco Vaccine and Prevention UnitUM1AI069496 · NIAID · PUBLIC HEALTH FOUNDATION ENTERPRISES · PI Susan Buchbinder, Diane V Havlir · 2012 to 2026
$30.5M
Identifying Optimal Treatment Strategies for Tuberculosis TreatmentR01AI135124 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ALLAND, DAVID, SAVIC, RADOJKA · 2019 to 2023
$3.8M
Novel Biomarkers to Shorten TB TreatmentR01AI126788 · NIAID · RBHS-NEW JERSEY MEDICAL SCHOOL · PI ALLAND, DAVID, DORMAN, SUSAN E · 2016 to 2020
$3.5M
Safety and tolerability of new and repurposed drugs for MDR-TB treatmentK08AI141740 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VELASQUEZ, GUSTAVO EDUARDO · 2019 to 2023
$985k
Mentoring Investigators in HIV and Tuberculosis Therapeutics ResearchK24AI150349 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DOOLEY, KELLY E. · 2020 to 2025
$789k
GenentechMédecins Sans Frontières SPHQ15-LOA-045National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention 200-2009-32582National Institute of Allergy and Infectious DiseasesNIAID NIH HHS K08 AI141740NIAID NIH HHS K24 AI150349NIAID NIH HHS R01 AI126788NIAID NIH HHS R01 AI135124NIAID NIH HHS UM1 AI069496NIAID NIH HHS UM1 AI106701NIH HHS UM1 AI068634SanofiUCSFUSAID 7200AA22CA00005
6 · The paper itself

Abstract

backgroundThe optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes.

methodsWe analyzed rifampicin concentration time profiles using population nonlinear mixed-effects models. We compared simulated rifampicin exposure from flat- and weight-banded dosing. We evaluated the effect of rifampicin exposure on stable culture conversion at 6 months; TB-related unfavorable outcomes at 9, 12, and 18 months using Cox proportional hazard models; and all trial-defined safety outcomes using logistic regression.

resultsOur model-derived rifampicin exposure ranged from 4.57 mg · h/L to 140.0 mg · h/L with a median of 41.8 mg · h/L. Pharmacokinetic simulations demonstrated that flat-dosed rifampicin provided exposure coverage similar to the weight-banded dose. Exposure-efficacy analysis (n = 680) showed that participants with rifampicin exposure below the median experienced similar hazards of stable culture conversion and TB-related unfavorable outcomes compared with those with exposure above the median. Exposure-safety analysis (n = 722) showed that increased rifampicin exposure was not associated with increased grade 3 or higher adverse events or serious adverse events.

conclusionsFlat-dosing of rifampicin at 600 mg daily may be a reasonable alternative to the incumbent weight-banded dosing strategy for the standard-of-care 6-month regimen. Future research should assess the optimal dosing strategy for rifampicin, at doses higher than the current recommendation.

Indexed as

RifampinTuberculosisAdolescentAdultAgedAntitubercular AgentsDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedTreatment OutcomeYoung AdultAntitubercular AgentsRifampinflat-dosingpopulation pharmacokineticsrifampicintuberculosisweight-banded dosing

Identifiers

PMID38462673
PMCPMC11175687
OpenAlexW4392637042

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.