Oral versus intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency: a pragmatic, randomised, multicentre, non-inferiority clinical trial undertaken in the primary healthcare setting (Project OB12).
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
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.


CONCLUSIONS
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.


BACKGROUND
This trial has been registered with ClinicalTrials.gov, number NCT 01476007, and under EUDRACT number 2010-024129-20.
Unidad de Apoyo a la Investigación, Gerencia Atención Primaria, Servicio Madrileño de Salud, Calle Espronceda 24, Madrid 28003, Spain. teresa.sanzcu@salud.madrid.org
Teresa
T
Sanz-Cuesta
Paloma
P
González-Escobar
Rosario
R
Riesgo-Fuertes
Sofía
S
Garrido-Elustondo
Isabel
I
del Cura-González
Jesús
J
Martín-Fernández
Esperanza
E
Escortell-Mayor
Francisco
F
Rodríguez-Salvanés
Marta
M
García-Solano
Rocío
R
González-González
María Ángeles
MÁ
Martín-de la Sierra-San Agustín
Carmen
C
Olmedo-Lucerón
María Luisa
ML
Sevillano Palmero
Carmen
C
Mateo-Ruiz
Beatriz
B
Medina-Bustillo
Antonio
A
Valdivia-Pérez
Francisca
F
García-de Blas-González
José Enrique
JE
Mariño-Suárez
Ricardo
R
Rodríguez-Barrientos
Gloria
G
Ariza-Cardiel
Luisa María
LM
Cabello-Ballesteros
Elena
E
Polentinos-Castro
Milagros
M
Rico-Blázquez
Ma Teresa
MT
Rodríguez-Monje
Sonia
S
Soto-Díaz
Susana
S
Martín-Iglesias
Ramón
R
Rodríguez-González
Irene
I
Bretón-Lesmes
María
M
Vicente-Herrero
Jesús
J
Sánchez-Díaz
Tomás
T
Gómez-Gascón
Mercedes
M
Drake-Canela
Ángel
Á
Asúnsolo-del Barco
D000284:Administration, Oral; D000368:Aged; D057186:Comparative Effectiveness Research; D004333:Drug Administration Routes; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D010349:Patient Compliance; D017060:Patient Satisfaction; D011320:Primary Health Care; D011788:Quality of Life / Q000523:psychology; D012107:Research Design; D018401:Sample Size; D012959:Socioeconomic Factors; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D014806:Vitamin B 12 Deficiency / Q000188:drug therapy* / Q000453:epidemiology; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000627:therapeutic use*
D014803:Vitamin B Complex; D014805:Vitamin B 12