1. Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care: a pragmatic, randomised, non-inferiority clinical trial (OB12)
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Teresa Sanz-Cuesta, Esperanza Escortell-Mayor, Isabel Cura-Gonzalez, Jesus Martin-Fernandez, Rosario Riesgo-Fuertes, Sofía Garrido-Elustondo, Jose Enrique Mariño-Suárez, Mar Álvarez-Villalba, Tomás Gómez-Gascón, Inmaculada González-García, Paloma González-Escobar, Concepción Vargas-Machuca Cabañero, Mar Noguerol-Álvarez, Francisca García de Blas-González, Raquel Baños-Morras, Concepción Díaz-Laso, Nuria Caballero-Ramírez, Alicia Herrero de-Dios, Rosa Fernández-García, Jesús Herrero-Hernández, Belen Pose-García, María Luisa Sevillano-Palmero, Carmen Mateo-Ruiz, Beatriz Medina-Bustillo, Monica Aguilar-Jiménez, Isabel Gutiérrez-Sánchez, Ángeles Fernández-Abad, José Antonio Granados-Garrido, Javier Martínez-Suberviola, Margarita Beltejar-Rodríguez, Carmen Coello-Alarcón, Susana Diez-Arjona, Ana Ballarín-González, Ignacio Iscar-Valenzuela, José Luis Quintana-Gómez, José Antonio González-Posada-Delgado, Enrique Revilla-Pascual, Esther Gómez-Suarez, Yolanda Fernández-Fernández, Fernanda Morales-Ortiz, Isabel Ferrer-Zapata, Esperanza Duralde-Rodríguez, Milagros Beamud-Lagos, Mª del Pilar Serrano-Simarro, Cristina Montero-García, María Domínguez-Paniagua, Sofía Causín-Serrano, Josefa San Vicente-Rodríguez, Germán Reviriego-Jaén, Margarita Camarero-Shelly, Rosa Gómez-del Forcallo, María Ángeles Miguel-Abanto, Lourdes Reyes-Martínez, Alejandro Rabanal-Basalo, Carolina Torrijos-Bravo, Pilar Gutiérrez-Valentín, Jorge Gómez-Ciriano, Susana Parra Román, Judit León-González, Mª José Nebril-Manzaneque, Juana Caro-Berzal, Alberto López-García-Franco, Sonia Redondo de-Pedro, Juan Carlos García-Álvarez, Elisa Viñuela-Beneitez, Marisa López-Martín, Nuria Sanz-López, Ana María Ibarra-Sánchez, Cecilio Gómez-Almodóvar, Javier Muñoz-Gutiérrez, Carmen Molins-Santos, Cristina Cassinello-Espinosa, Antonio Molina-Siguero, Rafael Sáez-Jiménez, Paloma Rodríguez-Almagro, Eva María Rey-Camacho, María Carmen Pérez-García, Antonio Redondo-Horcajo, Beatriz Pajuelo-Márquez, Encarnación Cidoncha-Calderón, Jesús Galindo Rubio, RosaAna Escriva Ferrairo, José Francisco Ávila-Tomas, Francisco De-Alba-Gómez, Mª Jesús Gómez-Martín, Alma María Fernández-Martínez, Rosa Feijoó-Fernández, José Vizcaíno-Sánchez-Rodrigo, Victoria Díaz-Puente, Felisa Núñez-Sáez, Luisa Asensio-Ruiz, Agustín Sánchez-Sánchez, Orlando Enríquez-Dueñas, Silvia Fidel-Jaimez, Rafael Ruiz-Morote-Aragón, Asunción Pacheco-Pascua, Belén Soriano-Hernández, Eva Álvarez-Carranza, Carmen Siguero-Pérez, Ana Morán-Escudero, María Martín-Martín, Francisco Vivas-Rubio, Rafael Pérez-Quero, Mª Isabel Manzano-Martín, César Redondo-Luciáñez, Nuria Tomás-García, Carlos Díaz-Gómez-Calcerrada, Julia Isabel Mogollo-García, Inés Melero-Redondo, Ricardo González-Gascón, María Carmen Álvarez-Orviz, María Veredas González-Márquez, Teresa SanClemente-Pastor, Amparo Corral-Rubio, Asunción Prieto-Orzanco, Cristina dela Cámara-Gonzalez, Mercedes Parrilla-Laso, Mercedes Canellas-Manrique, Maria Eloisa Rogero-Blanco, Paulino Cubero-González, Sara Sanchez-Barreiro, Mª Ángeles Aragoneses-Cañas, Ángela Auñón-Muelas, Olga Álvarez Montes, Petra María Cortes-Duran, Pilar Tardaguila-Lobato, Mar Escobar Gallegos, Antonia Pérez-de-Colosia-Zuil, Jaime Inneraraty-Martínez, María Jesús Bedoya-Frutos, María Teresa López-López, Nelly Álvarez-Fernández, Teresa Fontova-Cemeli, Josefa Marruedo-Mateo, Josefa Díaz-Serrano, Beatriz Pérez-Vallejo, Pilar Hombrados-Gonzalo, Marta Quintanilla-Santamaría, Yolanda González-Pascual, Luisa María Andrés-Arreaza, Soledad Escolar-Llamazares, Cristina Casado-Rodríguez, Luzdel Rey-Moya, Jesús Fernández-Valderrama, Alejandro Medrán-López, Julia Alonso-Arcas, Alejandra Rabanal-Carrera, Araceli Garrido-Barral, Milagros Velázquez-García, Azucena Sáez-Berlanga, Pilar Pérez-Egea, Pablo Astorga-Díaz, Carlos Casanova-García, Ana Isabel Román-Ruiz, Carmen Belinchón-Moya, Margarita Encinas-Sotillo, Virtudes Enguita-Pérez, Ester Valdés-Cruz, Consuelo Mayoral-López, Teresa Gijón-Seco, Francisca Martínez-Vallejo, Jesica Colorado-Valera, Ana Sosa-Alonso, Jeannet Sánchez-Yépez, Dolores Serrano-González, Beatriz López-Serrano, Inmaculada Santamaría-López, Paloma Morso-Peláez, Carolina López-Olmeda, Almudena García-Uceda-Sevilla, Mercedes delPilar Fernández-Girón, Leonor González-Galán, Mariano Rivera-Moreno, Luis Nistal Martín-de-Serranos, Mª Jesús López-Barroso, Margarita Torres-Parras, María Verdugo-Rosado, Mª Reyes Delgado-Pulpón, Elena Alcalá-Llorente, Sonsoles Muñoz-Moreno, Isabel Vaquero-Turiño, Ana María Sánchez-Sempere, FranciscoJavier Martínez-Sanz, Clementa Sanz-Sanchez, AnaMaría Arias-Esteso, Diego Martín-Acicoya, Pilar Kloppe-Villegas, Francisco Javier San-Andrés-Rebollo, Magdalena Canals-Aracil, Isabel García-Amor, Nieves Calvo-Arrabal, María Milagros Jimeno-Galán, Gloriade la Sierra-Ocaña, María Mercedes Araujo-Calvo, Julia Timoner-Aguilera, María Santos Santander-Gutiérrez, Alicia Mateo-Madurga, Ricardo Rodríguez-Barrientos, Milagros Rico-Blázquez, Juan Carlos Gil-Moreno, Mariel Morey-Montalvo, Amaya Azcoaga Lorenzo, Gloria Ariza-Cardiel, Elena Polentinos-Castro, Sonia Soto-Díaz, Mª Teresa Rodríguez-Monje, Susana Martín-Iglesias, Francisco Rodríguez-Salvanés, Marta García-Solano, Rocío González-González, María Vicente Herrero, Ramón Rodríguez-González, Irene Bretón-Lesmes, Martadel Alamo Camuñas, Anabel Sánchez Espadas, Marisa Serrano Olmeda, and Mª Angeles Gálvez Múgica
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Medicine - Abstract
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.Trial registration numbers NCT 01476007; EUDRACT (2010-024129-20).
- Published
- 2020
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