Ángel Asúnsolo del Barco, Jesús Sánchez-Díaz, Francisco Rodríguez-Salvanés, Sonia Soto-Díaz, Jose Enrique Mariño-Suárez, Carmen Olmedo-Lucerón, Isabel del Cura-González, Mercedes Drake-Canela, María Vicente-Herrero, María Luisa Sevillano Palmero, Rosario Riesgo-Fuertes, Beatriz Medina-Bustillo, Luisa Cabello-Ballesteros, Tomás Gómez-Gascón, Marta García-Solano, Esperanza Escortell-Mayor, Elena Polentinos-Castro, Paloma González-Escobar, Ricardo Rodríguez-Barrientos, Antonio Valdivia-Pérez, Francisca García de Blas-González, Mª Teresa Rodríguez-Monje, Rocío González-González, Gloria Ariza-Cardiel, Milagros Rico-Blázquez, Teresa Sanz-Cuesta, Susana Martín-Iglesias, Sofía Garrido-Elustondo, María Ángeles Martín-de la Sierra-San Agustín, Irene Bretón-Lesmes, Carmen Mateo-Ruiz, Ramón Rodríguez-González, and Jesús Martín-Fernández
Background 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. Discussion 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. Trial registration This trial has been registered with ClinicalTrials.gov, number NCT 01476007, and under EUDRACT number 2010-024129-20.