High-dose vitamin D3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial

被引：454

作者：

Martineau, Adrian R. ^{[1
,4
]}

Timms, Peter M. ^{[5
]}

Bothamley, Graham H. ^{[5
]}

Hanifa, Yasmeen ^{[1
]}

Islam, Kamrul ^{[1
]}

Claxton, Alleyna P. ^{[5
]}

Packe, Geoffrey E. ^{[6
]}

Moore-Gillon, John C. ^{[7
,8
]}

Darmalingam, Mathina ^{[9
]}

Davidson, Robert N. ^{[10
]}

Milburn, Heather J. ^{[11
]}

Baker, Lucy V. ^{[12
]}

Barker, Richard D. ^{[13
]}

Woodward, Nicholas J. ^{[14
]}

Venton, Timothy R. ^{[5
]}

Barnes, Korina E. ^{[5
]}

Mullett, Christopher J. ^{[5
]}

Coussens, Anna K. ^{[4
]}

Rutterford, Clare M. ^{[1
]}

Mein, Charles A. ^{[3
]}

Davies, Geraint R. ^{[15
]}

Wilkinson, Robert J. ^{[4
]}

Nikolayevskyy, Vladyslav ^{[2
]}

Drobniewski, Francis A. ^{[2
]}

Eldridge, Sandra M. ^{[1
]}

Griffiths, Christopher J. ^{[1
]}

机构：

[1] Queen Mary Univ London, Barts & London Sch Med & Dent, London E1 2AT, England

[2] Barts & London Queen Marys Sch Med & Dent, HPA Natl Mycobacterium Reference Lab, London, England

[3] Barts & London Queen Marys Sch Med & Dent, Genome Ctr, London, England

[4] Natl Inst Med Res, Div Mycobacterial Res, London NW7 1AA, England

[5] Homerton Univ NHS Fdn Trust, London, England

[6] Newham Chest Clin, London, England

[7] St Bartholomews Hosp, Dept Resp Med, London, England

[8] Royal London Hosp, Dept Resp Med, London E1 1BB, England

[9] Whipps Cross Univ Hosp, Dept Resp Med, London, England

[10] Northwick Pk Hosp & Clin Res Ctr, TB Clin, Harrow HA1 3UJ, Middx, England

[11] Guys & St Thomas NHS Fdn Trust, Dept Resp Med, London, England

[12] Lewisham Hosp, Dept Resp Med, London, England

[13] Kings Coll London, Dept Resp Med, London WC2R 2LS, England

[14] Royal Free Hosp, Dept Radiol, London NW3 2QG, England

[15] Univ Liverpool, Sch Clin Sci, Liverpool L69 3BX, Merseyside, England

来源：

LANCET | 2011年 / 377卷 / 9761期

关键词：

MESSENGER-RNA STABILITY; MYCOBACTERIUM-TUBERCULOSIS; CLINICAL-TRIAL; POLYMORPHISMS; CATHELICIDIN; RIFAMPICIN; SURVIVAL; OUTCOMES; DENSITY;

D O I：

10.1016/S0140-6736(10)61889-2

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 D3. 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 D3 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.

引用

页码：242 / 250

页数：9

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