Evidence map›Paper›PMID 27567500›Full record

ArticleBMC infectious diseases2016

Evaluation of high-dose rifampin in patients with new, smear-positive tuberculosis (HIRIF): study protocol for a randomized controlled trial.

Meredith Milstein, Leonid Lecca, Charles Peloquin, Denis Mitchison, Kwonjune Seung, Marcello Pagano, David Coleman, Elna Osso, Julia Coit, Dante Elmo Vargas Vasquez and 5 more

2 registry-linked trialsAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 18 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 2 pooled it
–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.

NCT01408914 phase2completednot on this map

Randomized Trial of High-Dose Rifampin in Patients With New, Smear-Positive TB

TypeinterventionalSponsorHarvard University Faculty of MedicineRan2013 to 2016Enrolled180ConditionsTuberculosisArmsHigher-Dose Rifampin
NCT03982277 phase2completednot on this mapstarted 2019, after this paper: background citation

A Randomized, Four-arm Open Label Phase Two-b Clinical Trial to Evaluate the Pharmacokinetics, Safety/Tolerability and Efficacy of High Dose Rifampicin in TB-HIV Co-infected Patients on Efavirenz- or Dolutegravir-based Antiretroviral Therapy

TypeinterventionalSponsorMakerere UniversityRan2019 to 2021Enrolled130ConditionsTuberculosisArmsRifampin 300 Mg Oral Capsule
3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. A systematic review and meta-analysis of first-line tuberculosis drug concentrations and treatment outcomes.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2020
    Pooled it
  2. Pooled it
  3. Efficacy and Safety of High-Dose Rifampin in Pulmonary Tuberculosis. A Randomized Controlled Trial.American journal of respiratory and critical care medicine · 2018
    Trial
  4. Trial
  5. Pharmacokinetic and pharmacogenomic predictors of hepatotoxicity in the HIRIF trial for drug-susceptible tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
    Article
  6. Review
  7. An Overview of Various Rifampicin Analogs againstMedicinal chemistry (Shariqah (United Arab Emirates)) · 2024
    Review
  8. Clinical impact of plasma concentrations of first-line antituberculosis drugs.South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde · 2023
    Article
  9. Article
  10. Rifampicin Can Be Given as Flat-Dosing Instead of Weight-Band Dosing.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020
    Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Observational
  16. Article
  17. Review
  18. Shortened tuberculosis treatment regimens: what is new?Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia
    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

15 authors.

Meredith MilsteinHarvard Medical School, Boston, MA, 02118, USA.
Leonid LeccaPartners In Health, Boston, MA, 02215, USA.
Charles PeloquinUniversity of Florida, Gainesville, FL, USA.
Denis MitchisonSt. Georges University, London, UK.
Kwonjune SeungPartners In Health, Boston, MA, 02215, USA.
Marcello PaganoHarvard School of Public Health, Boston, MA, USA.
David ColemanSt. Georges University, London, UK.
Elna OssoHarvard Medical School, Boston, MA, 02118, USA.
Julia CoitHarvard Medical School, Boston, MA, 02118, USA.
Dante Elmo Vargas VasquezHospital Nacional Hipólito Unanue, El Augustino, Lima, Peru.
Epifanio Sanchez GaravitoHospital Nacional Sergio E. Bernales, Comas, Lima, Peru.
Roger CalderonPartners In Health, Boston, MA, 02215, USA.
Carmen ContrerasPartners In Health, Boston, MA, 02215, USA.
Geraint DaviesUniversity of Liverpool, Liverpool, UK.
Carole D MitnickHarvard Medical School, Boston, MA, 02118, USA. Carole_Mitnick@hms.harvard.edu.

Funding

Randomized Trial of High-Dose Rifampin in Patients with New Smear-Positive TBU01AI091429 · NIAID · HARVARD MEDICAL SCHOOL · PI DAVIES, GERAINT, MITNICK, CAROLE D. · 2011 to 2013
$8.5M
NIAID NIH HHS U01 AI091429
6 · The paper itself

Abstract

backgroundEvidence has existed for decades that higher doses of rifampin may be more effective, but potentially more toxic, than standard doses used in tuberculosis treatment. Whether increased doses of rifampin could safely shorten treatment remains an open question. METHODS/

designThe HIRIF study is a phase II randomized trial comparing rifampin doses of 20 and 15 mg/kg/day to the standard 10 mg/kg/day for the first 2 months of tuberculosis treatment. All participants receive standard doses of companion drugs and a standard continuation-phase treatment (4 months, 2 drugs). They are followed for 6 months post treatment. Study participants are adults with newly diagnosed, previously untreated, smear positive (≥2+) pulmonary tuberculosis. The primary outcome is rifampin area under the plasma concentration-time curve (AUC0-24) after at least 14 days of study treatment/minimum inhibitory concentration. 180 randomized participants affords 90 % statistical power to detect a difference of at least 14 mcg/mL*hr between the 20 mg/kg group and the 10 mg/kg group, assuming a loss to follow-up of up to 17 %. DISCUSSION: Extant evidence suggests the potential for increased doses of rifampin to shorten tuberculosis treatment duration. Early studies that explored this potential using intermittent, higher dosing were derailed by toxicity. Given the continued large, global burden of tuberculosis with nearly 10 million new cases annually, shortened regimens with existing drugs would offer an important advantage to patients and health systems.

trial registrationThis trial was registered with clinicaltrials.gov (registration number: NCT01408914 ) on 2 August 2011.

Indexed as

Randomized Controlled Trials as TopicAdministration, OralAdultAntitubercular AgentsClinical Trials, Phase II as TopicDose-Response Relationship, DrugHumansMulticenter Studies as TopicRifampinSputumTuberculosis, PulmonaryAntitubercular AgentsRifampinPharmacokineticsRandomized trialRifampi(ci)nTreatment shorteningTuberculosis

Identifiers

PMID27567500
PMCPMC5002098

What OpenQuestion holds

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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.