Evidence map›Paper›PMID 26394045›Full record

Trial reportPloS one2015

Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial.

Akhirunnesa Mily, Rokeya Sultana Rekha, S M Mostafa Kamal, Abu Saleh Mohammad Arifuzzaman, Zeaur Rahim, Lamia Khan, Md Ahsanul Haq, Khaliqu Zaman, Peter Bergman, Susanna Brighenti and 3 more

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

Trial report in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01580007 (Clinical Trial of Oral Phenylbutyrate and Vitamin D Adjunctive Therapy in Pulmonary Tuberculosis in Bangladesh), which is not on this map. Cited by 106 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed, 10 pooled it
8.0field-weighted citation impact, top 2% 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.

NCT01580007 phase2completednot on this map

Clinical Trial of Oral Phenylbutyrate and Vitamin D Adjunctive Therapy in Pulmonary Tuberculosis in Bangladesh: a Pilot Study

TypeinterventionalSponsorInternational Centre for Diarrhoeal Disease Research, BangladeshRan2010 to 2014Enrolled288ConditionsPulmonary TuberculosisArmsActive Sodium Phenylbutyrate and active cholecalciferol, Placebo Sodium Phenylbutyrate plus active cholecalciferol, Active Sodium Phenylbutyrate and placebo cholecalciferol, Placebo Sodium Phenylbutyrate plus placebo cholecalciferol
3 · Its place in the literature

Who cites it

106 citing papers in PubMed, 10 syntheses or guidelines pooled it, 168 citations in OpenAlex.

  1. Pooled it
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  4. Treatment Effect Measures for Culture Conversion Endpoints in Phase IIb Tuberculosis Treatment Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021
    Pooled it
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  8. Pooled it
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  10. Nutritional supplements for people being treated for active tuberculosis.The Cochrane database of systematic reviews · 2016
    Pooled it
  11. Trial
  12. Daily adjunctive therapy with vitamin DJournal of internal medicine · 2018
    Trial
  13. High-Dose Vitamin DAmerican journal of respiratory and critical care medicine · 2017
    Trial
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Review
  20. Review

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

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

13 authors at 5 institutions in 3 countries.

Akhirunnesa MilyInternational Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka-1212 Bangladesh.
Rokeya Sultana RekhaInternational Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka-1212 Bangladesh; Department of Laboratory Medicine, Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
S M Mostafa KamalNational Institute of the Diseases of the Chest and Hospital, Mohakhali, Dhaka, Bangladesh.
Abu Saleh Mohammad ArifuzzamanInternational Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka-1212 Bangladesh.
Zeaur RahimInternational Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka-1212 Bangladesh.
Lamia KhanInternational Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka-1212 Bangladesh.
Md Ahsanul HaqInternational Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka-1212 Bangladesh.
Khaliqu ZamanInternational Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka-1212 Bangladesh.
Peter BergmanDepartment of Laboratory Medicine, Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Susanna BrighentiCenter for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Gudmundur H GudmundssonBiomedical Center, University of Iceland, 101 Reykjavik, Iceland.
Birgitta AgerberthDepartment of Laboratory Medicine, Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Rubhana RaqibInternational Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka-1212 Bangladesh.
International Centre for Diarrhoeal Disease Research · BDKarolinska Institutet · SEKarolinska University Hospital · SENational Institute of Cardiovascular Diseases · BDUniversity of Iceland · IS

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDevelopment of new tuberculosis (TB) drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D3 (vitD3) and 4-phenyl butyrate (PBA) are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects.

objectiveTo examine if oral adjunctive therapy with 5,000IU vitD3 or 2x500 mg PBA or PBA+vitD3 to standard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients.

methodsAdult TB patients (n = 288) were enrolled in a randomized, double-blind, placebo-controlled trial conducted in Bangladesh. Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8. Clinical assessments and sputum smear microscopy were performed weekly up to week 4, fortnightly up to week 12 and at week 24; TB culture was performed at week 0, 4 and 8; concentrations of LL-37 in cells, 25-hydroxyvitamin D3 (25(OH)D3) in plasma and ex vivo bactericidal function of monocyte-derived macrophages (MDM) were determined at week 0, 4, 8, 12 and additionally at week 24 for plasma 25(OH)D3.

resultsAt week 4, 71% (46/65) of the patients in the PBA+vitD3-group (p = 0.001) and 61.3% (38/62) in the vitD3-group (p = 0.032) were culture negative compared to 42.2% (27/64) in the placebo-group. The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD3-group (p = 0.001) and 2.2 times higher in vitD3-group (p = 0.032) compared to placebo. The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 (p = 0.034). Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo (log rank 11.38, p = 0.01).

conclusionAdjunct therapy with PBA+vitD3 or vitD3 or PBA to standard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host-directed-therapy in the treatment of TB.

trial registrationclinicaltrials.gov NCT01580007.

Indexed as

Administration, OralAdultAntimicrobial Cationic PeptidesAntitubercular AgentsCalcifediolCalciumCathelicidinsCholecalciferolC-Reactive ProteinDouble-Blind MethodDrug Therapy, CombinationFemaleHumansLeukocytes, MononuclearLogistic ModelsMacrophages4-phenylbutyric acidAntimicrobial Cationic PeptidesAntitubercular AgentsCalcifediolCalciumCathelicidinsCholecalciferolC-Reactive ProteinPhenylbutyratesRNA, Messenger

Identifiers

PMID26394045
PMCPMC4578887
OpenAlexW2210874704

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.