高剂量维生素 D（3）在肺结核强化期抗菌治疗中的应用：一项双盲随机对照试验。
High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial.
机构信息
Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK.
出版信息
Lancet. 2011 Jan 15;377(9761):242-50. doi: 10.1016/S0140-6736(10)61889-2. Epub 2011 Jan 5.
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 D(3). 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 D(3) 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.
FUNDING
British Lung Foundation.
背景
在抗生素问世之前，维生素 D 曾被用于治疗肺结核，其代谢产物可在体外诱导抗分枝杆菌免疫。目前尚无关于辅助应用维生素 D 治疗痰培养转阴的临床试验。
方法
我们在英国伦敦开展了一项多中心、随机对照试验，纳入了痰涂片阳性肺结核成人患者，将其随机分至维生素 D 治疗组（25μg 维生素 D3）或安慰剂组，于基线和开始标准抗结核治疗后第 14、28 和 42 天接受治疗。主要终点是从开始抗菌治疗到痰培养转为阴性的时间。对患者的维生素 D 受体 TaqI 和 FokI 多态性进行了基因分型，并进行了交互作用分析，以评估维生素 D 受体基因型对维生素 D3 反应的影响。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00419068。
结果
共有 126 例患者纳入主要疗效分析（干预组 62 例，安慰剂组 64 例）。干预组的中位痰培养转阴时间为 36.0 天，安慰剂组为 43.5 天（校正后 HR 为 1.39，95%CI 0.90-2.16；p=0.14）。TaqI 基因型改变了维生素 D 补充对痰培养转阴时间的影响（p（交互作用）=0.03），仅 tt 基因型患者观察到反应增强（8.09，95%CI 1.36-48.01；p=0.02）。FokI 基因型未改变维生素 D 补充的效果（p（交互作用）=0.85）。第 56 天，干预组和安慰剂组的平均血清 25-羟维生素 D 浓度分别为 101.4 nmol/L 和 22.8 nmol/L（差值的 95%CI 为 68.6-88.2；p<0.0001）。
结论
在接受肺结核强化期治疗的患者中，给予 4 剂 2.5mg 维生素 D3 可提高血清 25-羟维生素 D 浓度。维生素 D 对整个研究人群的痰培养转阴时间没有显著影响，但它显著加快了 TaqI 维生素 D 受体多态性 tt 基因型患者的痰培养转阴。
资助
英国肺脏基金会。
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