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

• Published in: The Lancet (British edition) 2011, Vol.377 (9761), p.242-250
• Main Authors: Martineau, Adrian R, Dr, Timms, Peter M, FRCPath, Bothamley, Graham H, FRCP, Hanifa, Yasmeen, MRCGP, Islam, Kamrul, BSc, Claxton, Alleyna P, FRCPath, Packe, Geoffrey E, FRCP, Moore-Gillon, John C, FRCP, Darmalingam, Mathina, FCPSA, Davidson, Robert N, MD, Milburn, Heather J, FRCP, Baker, Lucy V, FRCP, Barker, Richard D, MD, Woodward, Nicholas J, FRCR, Venton, Timothy R, FIBMS, Barnes, Korina E, FIBMS, Mullett, Christopher J, BSc, Coussens, Anna K, PhD, Rutterford, Clare M, MSc, Mein, Charles A, DPhil, Davies, Geraint R, MRCP, Wilkinson, Robert J, Prof, Nikolayevskyy, Vladyslav, PhD, Drobniewski, Francis A, Prof, Eldridge, Sandra M, Prof, Griffiths, Christopher J, Prof
• Format: Article
• Language: English
• Subjects: Bacterial diseases; Bacterial diseases of the respiratory system; Biological and medical sciences; General aspects; Human bacterial diseases; Infectious diseases; Internal Medicine; Medical sciences; Tuberculosis and atypical mycobacterial infections
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(10)61889-2

Summary 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 D3 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 Taq I and Fok I 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). Taq I genotype modified the effect of vitamin D supplementation on time to sputum culture conversion (pinteraction =0·03), with enhanced response seen only in patients with the tt genotype (8·09, 95% CI 1·36–48·01; p=0·02). Fok I genotype did not modify the effect of vitamin D supplementation (pinteraction =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