Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised,
double-blind, placebo-controlled trial.
Author(s): Daley P(1), Jagannathan V(2), John KR(3), Sarojini J(2), Latha A(2), Vieth R(4),
Suzana S(2), Jeyaseelan L(2), Christopher DJ(2), Smieja M(5), Mathai D(6).
Affiliation(s): Author information:
(1)Memorial University, St John's, NL, Canada. Electronic address: pkd336@mun.ca.
(2)Christian Medical College, Vellore, India. (3)SRM Medical College and Research
Centre, Chennai, India. (4)University of Toronto, ON, Canada. (5)McMaster
University, ON, Canada. (6)Apollo Institute of Medical Sciences and Research,
Hyderabad, India.
Publication date & source: 2015, Lancet Infect Dis. , 15(5):528-34
BACKGROUND: Vitamin D has immunomodulatory effects that might aid clearance of
mycobacterial infection. We aimed to assess whether vitamin D supplementation
would reduce time to sputum culture conversion in patients with active
tuberculosis.
METHODS: We did this randomised, double-blind, placebo-controlled, superiority
trial at 13 sites in India. Treatment-naive patients who were sputum-smear
positive, HIV negative, and had pulmonary tuberculosis were randomly assigned
(1:1), with centrally labelled, serially numbered bottles, to receive standard
active tuberculosis treatment with either supplemental high-dose oral vitamin D3
(four doses of 2·5 mg at weeks 0, 2, 4, and 6) or placebo. Neither the patients
nor the clinical and laboratory investigators and personnel were aware of
treatment assignment. The primary efficacy outcome was time to sputum culture
conversion. Analysis was by modified intention to treat. This trial is registered
with ClinicalTrials.gov, number NCT00366470.
FINDINGS: Between Jan 20, 2010, and Aug 23, 2011, we randomly assigned 247
participants to the vitamin D group (n=121) or the placebo group (n=126), of whom
211 participants (n=101 and n=110, respectively) were included in the primary
efficacy analysis. Median time to culture conversion in the vitamin D group was
43·0 days (95% CI 33·3-52·8) versus 42·0 days (33·9-50·1) in the placebo group
(log-rank p=0·95). Three (2%) patients died in the vitamin D group and one (1%)
patient died in the placebo group; no death was considered attributable to the
study intervention. No patients had hypercalcaemia.
INTERPRETATION: Our findings show that vitamin D supplementation did not reduce
time to sputum culture conversion. Further studies should investigate the role of
vitamin D in prevention or reactivation of tuberculosis infection.
FUNDING: Dalhousie University and Infectious Diseases Training and Research
Centre.
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