Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care: a pragmatic, randomised, non-inferiority clinical trial (OB12).

Autor:	Sanz-Cuesta T; Research Unit. Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain.; Health Services Research on Chronic Patients Network (REDISSEC), Instituto de Salud Carlos III, Madrid, Spain., Escortell-Mayor E; Research Unit. Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain.; Health Services Research on Chronic Patients Network (REDISSEC), Instituto de Salud Carlos III, Madrid, Spain., Cura-Gonzalez I; Research Unit. Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain isabel.cura@salud.madrid.org.; Health Services Research on Chronic Patients Network (REDISSEC), Instituto de Salud Carlos III, Madrid, Spain.; Preventive Medicine and Public Health Area, Health Sciences Faculty, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain., Martin-Fernandez J; Health Services Research on Chronic Patients Network (REDISSEC), Instituto de Salud Carlos III, Madrid, Spain.; Preventive Medicine and Public Health Area, Health Sciences Faculty, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain.; Multiprofessional Teaching Unit of Primary and Community Care Oeste. Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Riesgo-Fuertes R; Health Services Research on Chronic Patients Network (REDISSEC), Instituto de Salud Carlos III, Madrid, Spain.; Multiprofessional Teaching Unit of Primary and Community Care Sur, Gerencia Asistencial Atención Primaria, Madrid, Spain., Garrido-Elustondo S; Health Services Research on Chronic Patients Network (REDISSEC), Instituto de Salud Carlos III, Madrid, Spain.; Multiprofessional Teaching Unit of Primary and Community Care Sureste, Gerencia Asistencial Atención Primaria, Madrid, Spain., Mariño-Suárez JE; Healthcare Centre El Greco, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Álvarez-Villalba M; Health Services Research on Chronic Patients Network (REDISSEC), Instituto de Salud Carlos III, Madrid, Spain.; Healthcare Centre María Jesús Hereza, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Gómez-Gascón T; Health Services Research on Chronic Patients Network (REDISSEC), Instituto de Salud Carlos III, Madrid, Spain.; Fundación de Investigación e Innovación Biomédica de Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., González-García I; Healthcare Centre Barajas, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., González-Escobar P; Healthcare Centre Buenos Aires, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Vargas-Machuca Cabañero C; Healthcare Centre Guayaba, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Noguerol-Álvarez M; Healthcare Centre Cuzco, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., García de Blas-González F; Health Services Research on Chronic Patients Network (REDISSEC), Instituto de Salud Carlos III, Madrid, Spain.; Healthcare Centre Mendiguchía Carriche, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Baños-Morras R; Healthcare Centre Buenos Aires, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Díaz-Laso C; Healthcare Centre Fuentelarreina, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Caballero-Ramírez N; Healthcare Centre Juncal, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Herrero de-Dios A; Healthcare Centre Miguel de Cervantes, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Fernández-García R; Healthcare Centre Santa Isabel, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Herrero-Hernández J; Healthcare Centre Lavapiés, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Pose-García B; Healthcare Centre Mendiguchía Carriche, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Sevillano-Palmero ML; Pharmacy Department, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Mateo-Ruiz C; Pharmacy Department, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Medina-Bustillo B; Pharmacy Department, Gerencia Asistencial Atención Primaria, Servicio Madrileno de Salud, Madrid, Spain., Aguilar-Jiménez M; UICEC Hospital Ramón y Cajal. Plataforma SCReN, Hospital Ramón y Cajal; Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, Spain.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2020 Aug 20; Vol. 10 (8), pp. e033687. Date of Electronic Publication: 2020 Aug 20.
DOI:	10.1136/bmjopen-2019-033687
Abstrakt:	Objectives: To compare the effectiveness of oral versus intramuscular (IM) vitamin B 12 (VB12) in patients aged ≥65 years with VB12 deficiency. Design: Pragmatic, randomised, non-inferiority, multicentre trial in 22 primary healthcare centres in Madrid (Spain). Participants: 283 patients ≥65 years with VB12 deficiency were randomly assigned to oral (n=140) or IM (n=143) treatment arm. Interventions: The IM arm received 1 mg VB12 on alternate days in weeks 1-2, 1 mg/week in weeks 3-8 and 1 mg/month in weeks 9-52. The oral arm received 1 mg/day in weeks 1-8 and 1 mg/week in weeks 9-52. Main Outcomes: Serum VB12 concentration normalisation (≥211 pg/mL) at 8, 26 and 52 weeks. Non-inferiority would be declared if the difference between arms is 10% or less. Secondary outcomes included symptoms, adverse events, adherence to treatment, quality of life, patient preferences and satisfaction. Results: The follow-up period (52 weeks) was completed by 229 patients (80.9%). At week 8, the percentage of patients in each arm who achieved normal B 12 levels was well above 90%; the differences in this percentage between the oral and IM arm were -0.7% (133 out of 135 vs 129 out of 130; 95% CI: -3.2 to 1.8; p>0.999) by per-protocol (PPT) analysis and 4.8% (133 out of 140 vs 129 out of 143; 95% CI: -1.3 to 10.9; p=0.124) by intention-to-treat (ITT) analysis. At week 52, the percentage of patients who achieved normal B 12 levels was 73.6% in the oral arm and 80.4% in the IM arm; these differences were -6.3% (103 out of 112 vs 115 out of 117; 95% CI: -11.9 to -0.1; p=0.025) and -6.8% (103 out of 140 vs 115 out of 143; 95% CI: -16.6 to 2.9; p=0.171), respectively. Factors affecting the success rate at week 52 were age, OR=0.95 (95% CI: 0.91 to 0.99) and having reached VB12 levels ≥281 pg/mL at week 8, OR=8.1 (95% CI: 2.4 to 27.3). Under a Bayesian framework, non-inferiority probabilities (Δ>-10%) at week 52 were 0.036 (PPT) and 0.060 (ITT). Quality of life and adverse effects were comparable across groups. 83.4% of patients preferred the oral route. Conclusions: Oral administration was no less effective than IM administration at 8 weeks. Although differences were found between administration routes at week 52, the probability that the differences were below the non-inferiority threshold was very low. Trial Registration Numbers: NCT01476007; EUDRACT (2010-024129-20). Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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