Unidad de Apoyo a la Investigación, Gerencia Atención Primaria, Servicio Madrileño de Salud, Calle Espronceda 24, Madrid 28003, Spain.
BMC Public Health. 2012 May 31;12:394. doi: 10.1186/1471-2458-12-394.
The oral administration of vitamin B12 offers a potentially simpler and cheaper alternative to parenteral administration, but its effectiveness has not been definitively demonstrated. The following protocol was designed to compare the effectiveness of orally and intramuscularly administered vitamin B12 in the treatment of patients ≥65 years of age with vitamin B12 deficiency.
METHODS/DESIGN: The proposed study involves a controlled, randomised, multicentre, parallel, non-inferiority clinical trial lasting one year, involving 23 primary healthcare centres in the Madrid region (Spain), and patients ≥65 years of age. The minimum number of patients required for the study was calculated as 320 (160 in each arm). Bearing in mind an estimated 8-10% prevalence of vitamin B12 deficiency among the population of this age group, an initial sample of 3556 patients will need to be recruited. Eligible patients will be randomly assigned to one of the two treatment arms. In the intramuscular treatment arm, vitamin B12 will be administered as follows: 1 mg on alternate days in weeks 1 and 2, 1 mg/week in weeks 3-8,and 1 mg/month in weeks 9-52. In the oral arm, the vitamin will be administered as: 1 mg/day in weeks 1-8 and 1 mg/week in weeks 9-52. The main outcome variable to be monitored in both treatment arms is the normalisation of the serum vitamin B12 concentration at weeks 8, 26 and 52; the secondary outcome variables include the serum concentration of vitamin B12 (in pg/ml), adherence to treatment, quality of life (EuroQoL-5D questionnaire), patient 3satisfaction and patient preferences. All statistical tests will be performed with intention to treat and per protocol. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in analyses.
The results of this study should help establish, taking quality of life into account, whether the oral administration of vitamin B12 is an effective alternative to its intramuscular administration. If this administration route is effective, it should provide a cheaper means of treating vitamin B12 deficiency while inducing fewer adverse effects. Having such an alternative would also allow patient preferences to be taken into consideration at the time of prescribing treatment.
This trial has been registered with ClinicalTrials.gov, number NCT 01476007, and under EUDRACT number 2010-024129-20.
口服维生素 B12 提供了一种潜在的更简单、更便宜的替代方案，而其有效性尚未得到明确证实。本方案旨在比较口服和肌肉注射维生素 B12 治疗 65 岁及以上维生素 B12 缺乏症患者的疗效。
方法/设计：拟进行一项为期一年的、对照、随机、多中心、平行、非劣效性临床试验，涉及马德里地区（西班牙）的 23 个初级保健中心和 65 岁及以上的患者。计算得出该研究所需的最低患者人数为 320 例（每组 160 例）。鉴于该年龄段人群中维生素 B12 缺乏症的估计患病率为 8-10%，需要招募 3556 名初始患者。符合条件的患者将随机分配至两个治疗组之一。在肌肉注射治疗组中，维生素 B12 的使用方法如下：第 1 周和第 2 周隔日 1mg，第 3-8 周每周 1mg，第 9-52 周每月 1mg。在口服治疗组中，维生素的使用方法如下：第 1 周-第 8 周每天 1mg，第 9-52 周每周 1mg。两个治疗组中都需要监测的主要结局变量是第 8、26 和 52 周时血清维生素 B12 浓度的正常化；次要结局变量包括血清维生素 B12 浓度（pg/ml）、治疗依从性、生活质量（EuroQoL-5D 问卷）、患者满意度和患者偏好。所有统计检验均将采用意向治疗和方案进行。将使用带有随机效应的逻辑回归来调整预后因素。在分析中会考虑混杂因素或可能改变记录效果的因素。
本研究的结果应有助于确定口服维生素 B12 是否是肌肉注射的有效替代方法，同时考虑到生活质量。如果这种给药途径有效，它应该为治疗维生素 B12 缺乏症提供一种更便宜的方法，同时引起更少的不良反应。有了这样的替代方案，还可以在开处方治疗时考虑患者的偏好。
本试验已在 ClinicalTrials.gov 注册，编号为 NCT 01476007，并在 EUDRACT 编号为 2010-024129-20。
