Sanz-Cuesta, TeresaEscortell-Mayor, Esperanzadel Cura-González, IsabelMartín-Fernández, JesúsRiesgo-Fuertes, RosarioGarrido-Elustondo, SofíaMariño-Suárez, Jose EnriqueÁlvarez-Villalba, MarGómez-Gascón, TomásGonzález-García, InmaculadaGonzález-Escobar, PalomaVargas-Machuca Cabañero, ConcepciónNoguerol-Álvarez, MarGarcía de Blas-González, FranciscaBaños-Morras, RaquelDíaz-Laso, ConcepciónCaballero-Ramírez, NuriaHerrero de-Dios, AliciaFernández-García, RosaHerrero-Hernández, JesúsPose-García, BelenSevillano-Palmero, María LuisaMateo-Ruiz, CarmenMedina-Bustillo, BeatrizAguilar-Jiménez, Monicaand OB12 Group2025-01-022025-01-022020-05-30Sanz-Cuesta T, Escortell-Mayor E, Cura-Gonzalez I, Martin-Fernandez J, Riesgo-Fuertes R, Garrido-Elustondo S, Mariño-Suárez JE, Álvarez-Villalba M, Gómez-Gascón T, González-García I, González-Escobar P, Vargas-Machuca Cabañero C, Noguerol-Álvarez M, García de Blas-González F, Baños-Morras R, Díaz-Laso C, Caballero-Ramírez N, Herrero de-Dios A, Fernández-García R, Herrero-Hernández J, Pose-García B, Sevillano-Palmero ML, Mateo-Ruiz C, Medina-Bustillo B, Aguilar-Jiménez M; OB12 Group. Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care: a pragmatic, randomised, non-inferiority clinical trial (OB12). BMJ Open. 2020 Aug 20;10(8):e033687. doi: 10.1136/bmjopen-2019-033687. PMID: 32819927; PMCID: PMC7440823.2044-6055 (online)https://hdl.handle.net/10115/49617The trial was financed by Ministerio de Sanidad y Consumo Español through their call for independent clinical research, Orden Ministerial SAS/2377, 2010 (EC10-115, EC10-116, EC10-117, EC10-119, EC10-122); CAIBER—Spanish Clinical Research Network, Instituto de Salud Carlos III (ISCIII) (CAI08/010044); and Gerencia Asistencial de Atención Primaria de Madrid. This study is also supported by the Spanish Clinical Research Network (SCReN), funded by ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, project number PT13/0002/0007, within the National Research Program I+D+I 2013-2016 and co-funded with European Union ERDF funds (European Regional Development Fund). This project received a grant for the translation and publication of this article from the Foundation for Biomedical Research and Innovation in Primary Care (FIIBAP) Call 2017 for grants to promote research programs.Objectives: To compare the effectiveness of oral versus intramuscular (IM) vitamin B12 (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 B12 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 B12 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.enAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/administration oralequivalence trialinjections intramuscularpatient preferenceprimary health carevitamin B 12 deficiencyArticle10.1136/bmjopen-2019-033687info:eu-repo/semantics/openAccess