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

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 (?>-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).

SUBMITTER: Sanz-Cuesta T

PROVIDER: S-EPMC7440823 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Sanz-Cuesta Teresa T Escortell-Mayor Esperanza E Cura-Gonzalez Isabel I Martin-Fernandez Jesus J Riesgo-Fuertes Rosario R Garrido-Elustondo Sofía S Mariño-Suárez Jose Enrique JE Álvarez-Villalba Mar M Gómez-Gascón Tomás T González-García Inmaculada I González-Escobar Paloma P Vargas-Machuca Cabañero Concepción C Noguerol-Álvarez Mar M García de Blas-González Francisca F Baños-Morras Raquel R Díaz-Laso Concepción C Caballero-Ramírez Nuria N Herrero de-Dios Alicia A Fernández-García Rosa R Herrero-Hernández Jesús J Pose-García Belen B Sevillano-Palmero María Luisa ML Mateo-Ruiz Carmen C Medina-Bustillo Beatriz B Aguilar-Jiménez Monica M

BMJ open 20200820 8

<h4>Objectives</h4>To compare the effectiveness of oral versus intramuscular (IM) vitamin B<sub>12</sub> (VB12) in patients aged ≥65 years with VB12 deficiency.<h4>Design</h4>Pragmatic, randomised, non-inferiority, multicentre trial in 22 primary healthcare centres in Madrid (Spain).<h4>Participants</h4>283 patients ≥65 years with VB12 deficiency were randomly assigned to oral (n=140) or IM (n=143) treatment arm.<h4>Interventions</h4>The IM arm received 1 mg VB12 on alternate days in weeks 1-2, ...[more]

PMID: 32819927

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Project description:BackgroundThe 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/designThe 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.DiscussionThe 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.Trial registrationThis trial has been registered with ClinicalTrials.gov, number NCT 01476007, and under EUDRACT number 2010-024129-20.

Project description:The fertility of dairy cows is challenged during early lactation and better nutritional strategies need to be developed to address this issue. Combined supplementation of folic acid and vitamin B12 improves energy metabolism in the dairy cow during early lactation. Therefore, the present study was undertaken to explore the effects of this supplement on gene expression in granulosa cells from the dominant follicle during the postpartum period. Multiparous Holstein cows received weekly intramuscular injection of 320 mg folic acid and 10 mg vitamin B12 (treated group) beginning 24 (SD 4) d before calving until 56 d after calving, whereas the control group received saline. The urea plasma concentration was significantly decreased during the pre-calving period, and the concentration of both folate and vitamin B12 were increased in treated animals. Milk production and dry matter intake were not significantly different between the two groups. Plasma concentrations of folates and vitamin B12 were increased in vitamin-treated animals. Daily dry matter intake was not significantly different between the 2 groups before (13.5 kg SE 0.5) and after (23.6 kg SE 0.9) calving. Average energy-corrected milk tended to be greater in vitamin-treated cows, 39.7 (SE 1.4) and 38.1 (SE 1.3) kg/d for treated and control cows, respectively. After calving, average plasma concentration of BHBA tended to be lower in cows injected with the vitamin supplement, 0.47 (SE 0.04) vs. 0.55 (SE 0.03) for treated and control cows, respectively. The ovarian follicle ? 12 mm in diameter was collected by ovarian pick-up after estrus synchronization. Recovered follicular fluid volumes were greater in the vitamin-treated group. A microarray platform was used to investigate the impact of treatment on gene expression of granulosa cells. Lower expression of genes involved in the cell cycle and higher expression of genes associated with granulosa cell differentiation prior to ovulation were observed. Selected candidate genes were analyzed by reverse transcription quantitative polymerase chain reaction. Although the effects of intramuscular injections of folic acid and vitamin B12 on lactational performance and metabolic status of animals were limited, Ingenuity Pathway Analysis of gene expression in granulosa cells suggests a stimulation of cell differentiation in vitamin-treated cows, which may be the result of an increase in LH secretion. Two conditions experiment (Control and Treated). Granulosa cells from the 66h post second PGF2alpha injection. Biological replicates: 3 from each time point. Two technical replicates for each comparison (dye-swap).

Project description:ObjectiveTo compare the effect of intramuscular olanzapine with intramuscular haloperidol plus promethazine on rapid tranquillisation of agitated or violent people with mental illness.DesignPragmatic, allocation concealed, randomised controlled trial.SettingEmergency services of a general hospital psychiatry department in Vellore, south India.Participants300 adults with agitated or violent behaviour as a result of mental illness; 150 randomised to intramuscular olanzapine and 150 randomised to intramuscular haloperidol plus promethazine.InterventionsOpen treatment with intramuscular olanzapine or intramuscular haloperidol plus promethazine.Main outcome measuresPrimary outcome was proportion of patients who were tranquil or asleep at 15 minutes and 240 minutes. Secondary outcomes were proportion of patients who were tranquil, asleep, restrained, absconding, or clinically improved at 15, 30, 60, 120, and 240 minutes; additional medical interventions and adverse effects over four hours; and compliance with oral drugs and adverse effects over two weeks.ResultsOf 300 people randomised to receive either intramuscular olanzapine or intramuscular haloperidol plus promethazine, follow-up data were available for primary outcomes for 298 (99%). Both treatments resulted in similar proportions of people being tranquil or asleep at 15 minutes (olanzapine 131/150 (87%), haloperidol plus promethazine 136/150 (91%); relative risk 0.96, 95% confidence interval 0.34 to 1.47) and 240 minutes (olanzapine 144/150 (96%), haloperidol plus promethazine 145/150 (97%); relative risk 0.99, 0.95 to 1.03). However, more people given olanzapine than those given haloperidol plus promethazine required additional drugs over four hours (65/150 (43%) v 31/150 (21%); relative risk 2.07, 1.43 to 2.97). Adverse effects were uncommon with both treatments.ConclusionsIntramuscular olanzapine and intramuscular haloperidol plus promethazine were effective at rapidly tranquillising or sedating agitated or violent patients with mental illness but the combination resulted in fewer additional medical interventions within four hours of intervention.Trial registrationClinical trials NCT00455234 [ClinicalTrials.gov].

Dataset Information

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

Publications

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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