High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial.

Double-blind randomized controlled trial in adults with newly diagnosed pulmonary tuberculosis in Tbilisi, Georgia. Most participants were vitamin D deficient at baseline; the cohort included both drug-susceptible tuberculosis and a minority with MDR-TB, and HIV coinfection was uncommon.

Adjunctive vitamin D3 was given orally at a high dose: 50,000 IU (1.25 mg) three times weekly for 8 consecutive weeks, followed by 50,000 IU every 2 weeks for another 8 weeks, in addition to standard first-line anti-tuberculosis therapy. The comparator was placebo.

High-dose vitamin D3 corrected vitamin D deficiency and increased 25(OH)D levels, but it did not improve sputum culture conversion over 16 weeks. In 192 subjects with culture-confirmed tuberculosis, median time to culture conversion was 29 d with vitamin D3 versus 27 d with placebo (HR: 0.86, 95% CI: 0.63, 1.18; P = 0.33), and 8-week conversion rates were 84.0% versus 82.1% (P = 0.99). Adverse events and plasma calcium concentrations were similar between groups; hypercalcemia occurred in 3% versus 7% (P = 0.21). The overall conclusion was that this high-dose regimen did not enhance TB treatment outcomes, although a possible MDR-TB subgroup signal was not conclusive.

The trial was short for a tuberculosis outcome study and did not show benefit on the primary endpoint. Follow-up was incomplete for some participants, with 40 patients missing the week 16 visit and 7 culture-negative at baseline, and subgroup signals in MDR-TB were inconclusive. Generalizability is limited to a single center in Georgia with a population that was largely vitamin D deficient.