Introduction and objectives Existing trials of adjunctive vitamin D to enhance response to antimicrobial therapy for pulmonary tuberculosis are variously limited by relatively small sample sizes, inadequate dosing regimens and low baseline prevalence of vitamin D deficiency among participants. Our objective was to conduct a large randomised controlled trial of high-dose vitamin D in a setting where profound vitamin D deficiency was common in patients with pulmonary TB.
Methods We conducted a double-blind randomised placebo-controlled trial of high-dose adjunctive vitamin D3 in adults with sputum smear-positive pulmonary tuberculosis in Ulaanbaatar, Mongolia. 390 participants were allocated to receive 3.5 mg vitamin D3 (n = 190) or placebo (n = 200) at baseline and at 2, 4 and 6 weeks after starting standard tuberculosis treatment. The primary endpoint of the trial was time from initiation of antimicrobial therapy to sputum culture conversion. Secondary endpoints were time to sputum smear conversion, resolution of infiltrates on chest radiograph and serum 25-hydroxyvitamin D (25[OH]D) concentrations. This trial was registered with ClinicalTrials.gov (NCT01657656).
Results At baseline, 81% of participants had profound vitamin D deficiency (serum 25[OH]D <25 nmol/L). Vitamin D supplementation elevated 8-week serum 25(OH)D concentrations to high-physiological levels (154.5 in intervention arm vs. 15.2 nmol/L in placebo arm, 95% CI: for difference 125.9 to 154.7 nmol/L, P < 0.001), but did not influence time to sputum culture conversion (adjusted hazard ratio 1.11, 95% CI: 0.88 to 1.39, P = 0.39). Allocation to vitamin D was associated with accelerated sputum smear conversion (adjusted HR 1.47, 95% CI: 1.09 to 1.98, P = 0.01) and a small but statistically significant reduction in the mean number of zones affected on chest radiograph at 8 weeks (5.48 vs. 5.69, 95% CI: for difference 0.06 to 0.77 zones, p = 0.02).
Conclusions This is the largest randomised controlled trial to investigate effects of adjunctive vitamin D on time to sputum culture conversion in pulmonary tuberculosis conducted to date. Adjunctive high-dose vitamin D was effective in elevating serum 25(OH)D concentrations to high-physiological levels, but did not influence time to sputum culture conversion.