This is a multicentre project with 5 sub-projects (EC10-117, EC10-115, EC10-116, EC10-119, EC10-122). The Project involves about 200 professionals belonging to different categories from the ‘Gerencia de Atención Primaria de la Comunidad de Madrid’ (See People).
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.
Aim. To compare the effectiveness of orally and intramuscularly administered vitamin B12 in the normalisation of serum vitamin B12 concentrations at 8, 26 and 52 weeks of treatment, in patients aged ≥65 years with vitamin B12 deficiency treated at primary healthcare centres in the Madrid region, Spain.
Design. The proposed study involves a controlled, randomised, multicentre, parallel, non-inferiority clinical trial lasting one year. Setting: It involves 23 primary healthcare centres in the Madrid region (Spain). This trial has been registered with ClinicalTrials.gov, number NCT 01476007, and under EUDRACT (European Clinical Trials Database) number 2010-024129-20 and the protocol was approved by the Madrid Region Clinical Research Ethics Committee (Comité Ético de Investigación Clínica Regional).
Participants. Patients >/=65 years of age with vitamin B12 levels < 211 pg/ml. 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.
Intervention. 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.
Variables. 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 satisfaction and patient preferences.
Data collection. Cases of B12 deficiency will be screened at the screening visit. Patients in both arms will undergo analytical monitoring to assess levels normalize.
Statistical analysis. The trial will involve a descriptive statistical analysis of the baseline characteristics of patients in both treatment arms; Baseline comparisons; Analysis of effectiveness of treatment (main outcome) at the three monitoring points (All statistical tests will be performed with intention to treat and per protocol); Safety analysis; Quality of life analysis and Analysis of adherence treatment.
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.
Funding: Ministerio de Sanidad, Política Social e Igualdad. Orden SAS/2377/2010, de 7 de septiembre, por la que se establece la convocatoria para la concesión de ayudas para el fomento de la investigación clínica independiente. Convocatoria 2010: subproyectos EC10-117, EC10-115, EC10-116, EC10-119, EC10-122. Sponsor: Gerencia de Atención Primaria de la Comunidad de Madrid.