High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial
Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, Packe GE, Moore-Gillon JC, Darmalingam M, Davidson RN, Milburn HJ, Baker LV, Barker RD, Woodward NJ, Venton TR, Barnes KE, Mullett CJ, Coussens AK, Rutterford CM, Mein CA, Davies GR, Wilkinson RJ, Nikolayevskyy V, Drobniewski FA, Eldridge SM, Griffiths CJ
Lancet (London, England) · 401 citas
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- Wellcome Trust
- Gobierno
- National Institute for Health and Care Research
- Organización sin fines de lucro
- British Lung Foundation
- Gobierno
- Medical Research Council
- Gobierno
- National Institute for Health Research (NIHR)
- Subvenciones
- Wellcome Trust (088316); National Institute for Health and Care Research (NF-SI-0508-10212); Wellcome Trust (072070); Wellcome Trust (84323); British Lung Foundation (TB05/11)
Según 5 financiadores declarados.
Publicación
- Publicado
- 2011-01-01 · Lancet · vol. 377 · número 9761 · págs. 242–250
- Editorial
- Elsevier BV
- Citado
- 580 citas · más que el 100% de estudios similares · 49.7× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 44 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Tuberculosis Research and Epidemiology · Vitamin D Research Studies · Infectious Diseases and Tuberculosis
- Palabras clave
- vitamin D3 supplementation, pulmonary tuberculosis, sputum conversion, VDR polymorphisms, TaqI polymorphism, FokI polymorphism, 25-hydroxyvitamin D, adjunctive therapy, genetic interactions, tuberculosis treatment response, smear-positive tuberculosis, antimycobacterial immunity
- MeSH
- sputum, humans, tuberculosis, pulmonary, cholecalciferol, taq polymerase, vitamins, receptors, calcitriol, antitubercular agents, double-blind method, polymorphism, genetic, adult, female, male, young adult
26 autores
- Adrian R. Martineau🇬🇧 · autor de correspondenciaQueen Mary University of London
- Peter M Timms🇬🇧Homerton University Hospital; Homerton University Hospital NHS Foundation Trust
- Graham Henry Bothamley🇬🇧Homerton University Hospital; Homerton University Hospital NHS Foundation Trust
- Yasmeen Hanifa🇬🇧Queen Mary University of London
- Kamrul Islam🇬🇧Queen Mary University of London
- Alleyna P. Claxton🇬🇧Homerton University Hospital; Homerton University Hospital NHS Foundation Trust
- Geoffrey E. Packe
- John C. Moore-Gillon🇬🇧St Bartholomew's Hospital; Royal London Hospital
- Mathina Darmalingam🇬🇧Whipps Cross University Hospital
- Robert N. Davidson🇬🇧Northwick Park Hospital
- Heather June Milburn🇬🇧St Thomas' Hospital; Guy's and St Thomas' NHS Foundation Trust
- Lucy V. Baker🇬🇧University Hospital Lewisham
- Richard D. Barker🇬🇧King's College Hospital
- Nicholas Woodward🇬🇧The Royal Free Hospital
- Timothy R Venton🇬🇧Homerton University Hospital; Homerton University Hospital NHS Foundation Trust
- Korina E. Barnes🇬🇧Homerton University Hospital; Homerton University Hospital NHS Foundation Trust
- Christopher J Mullett🇬🇧Homerton University Hospital; Homerton University Hospital NHS Foundation Trust
- Anna K. Coussens
- Clare M. Rutterford🇬🇧Queen Mary University of London
- Charles A. Mein🇬🇧Queen Mary University of London
- Geraint Davies🇬🇧University of Liverpool
- Robert John Wilkinson
- Vladyslav Nikolayevskyy🇬🇧Queen Mary University of London
- Francis A. Drobniewski🇬🇧Queen Mary University of London
- Sandra M Eldridge🇬🇧Queen Mary University of London
- Chris Griffiths🇬🇧Queen Mary University of London
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
Vitamin D was used to treat tuberculosis in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in vitro. Clinical trials investigating the effect of adjunctive vitamin D on sputum culture conversion are absent.
Methods
We undertook a multicentre randomised controlled trial of adjunctive vitamin D in adults with sputum smear-positive pulmonary tuberculosis in London, UK. 146 patients were allocated to receive 2·5 mg vitamin D(3) or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment. The primary endpoint was time from initiation of antimicrobial treatment to sputum culture conversion. Patients were genotyped for TaqI and FokI polymorphisms of the vitamin D receptor, and interaction analyses were done to assess the influence of the vitamin D receptor genotype on response to vitamin D(3). This trial is registered with ClinicalTrials.gov number NCT00419068.
Findings
126 patients were included in the primary efficacy analysis (62 assigned to intervention, 64 assigned to placebo). Median time to sputum culture conversion was 36·0 days in the intervention group and 43·5 days in the placebo group (adjusted hazard ratio 1·39, 95% CI 0·90-2·16; p=0.14). TaqI genotype modified the effect of vitamin D supplementation on time to sputum culture conversion (p(interaction)=0·03), with enhanced response seen only in patients with the tt genotype (8·09, 95% CI 1·36-48·01; p=0·02). FokI genotype did not modify the effect of vitamin D supplementation (p(interaction)=0·85). Mean serum 25-hydroxyvitamin D concentration at 56 days was 101·4 nmol/L in the intervention group and 22·8 nmol/L in the placebo group (95% CI for difference 68·6-88·2; p<0·0001).
Interpretation
Administration of four doses of 2·5 mg vitamin D(3) increased serum 25-hydroxyvitamin D concentrations in patients receiving intensive-phase treatment for pulmonary tuberculosis. Vitamin D did not significantly affect time to sputum culture conversion in the whole study population, but it did significantly hasten sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism.
Funding
British Lung Foundation.
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