Oral Versus Intravenous Vitamin B12 Replacement in Hemodialysis Patients

Overview

The goal of this clinical trial is to learn whether intravenous (IV) vitamin B12 works better than oral vitamin B12 to correct vitamin B12 deficiency in adults on maintenance hemodialysis. The main questions it aims to answer are: Does IV vitamin B12 raise blood B12 levels more than oral vitamin B12 over four weeks? Does IV vitamin B12 lead to more patients reaching a normal blood B12 level than oral vitamin B12? Do the two routes differ in their effect on blood counts and nerve-related symptoms such as numbness and tingling? Participants will: Receive either an IV injection of vitamin B12 once a week after their dialysis session, or oral vitamin B12 tablets three times a day, for four weeks Have blood tests for vitamin B12 level and blood count at the start of the study and again at week 5 Be checked for nerve-related symptoms such as numbness and tingling at the start of the study and again at week 5 Researchers will compare IV vitamin B12 to oral vitamin B12 to see which route works better at correcting B12 deficiency in hemodialysis patients.

Vitamin B12 (cobalamin) deficiency is common among patients on maintenance hemodialysis (HD), driven by dietary restriction, impaired gastrointestinal absorption, increased metabolic demand, and loss of water-soluble vitamins during dialysis. Left uncorrected, deficiency contributes to anemia, peripheral neuropathy, cognitive impairment, and hyperhomocysteinemia, an established cardiovascular risk factor in this population. Cobalamin has traditionally been replaced by the intramuscular route, but intramuscular injection is painful and carries a risk of hematoma and bruising in HD patients because of the prophylactic heparin used during dialysis. This has driven a shift toward oral and intravenous (IV) supplementation. Existing randomized and network meta-analysis evidence shows that oral, intramuscular, and sublingual routes achieve comparable biochemical correction, but this evidence comes from populations with normal or near-normal renal function and does not include the IV route. Guidelines generally discourage IV cobalamin because more than three-quarters of an unbound IV dose is cleared in the urine within 24 hours. This rationale is not expected to apply to HD patients, who have little or no residual renal function and therefore negligible urinary loss of the drug, and in whom vascular access is already established for dialysis. Direct comparisons of oral versus IV cobalamin repletion specifically in the HD population are scarce, and the single trial to compare these routes head-to-head (Courage-12) was conducted in patients with normal renal function. This trial was designed to address that gap. Design. This was a quasi-experimental, two-arm, comparative study conducted at a single hemodialysis centre over a six-month period. Patients were not randomized; eligible patients presenting from successive dialysis shifts were allocated to the IV or oral arm according to the study protocol, with allocation managed to keep the two arms of comparable size (30 patients per arm, 60 total). Interventions. IV arm: Mecobalamin 1000 µg was given intravenously once weekly for four weeks. Each dose was drawn from a 1000 µg/mL ampoule, diluted in 10 mL of 0.9% sodium chloride, and administered by trained dialysis staff as a slow IV push over 3-5 minutes (not a rapid bolus); dextrose-containing diluents were avoided. The dose was given through the venous port of the extracorporeal circuit at the end of the HD session, immediately before rinse-back, so that the administered vitamin was not removed by the dialyzer. Ampoules were protected from light until the time of administration. Oral arm: Mecobalamin 500 µg tablets were given three times daily for four weeks. Adherence was reinforced verbally at each dialysis visit and verified by pill count at follow-up. Assessments. A structured proforma captured demographic and clinical data, dietary pattern, 24-hour urine output, dialysis vintage, and comorbidities at baseline. Total serum vitamin B12 was measured by enzyme-linked immunosorbent assay in the hospital laboratory at baseline and at week 5 (one week after the last dose), along with a complete blood count (hemoglobin, MCV, MCH, MCHC, hematocrit). Neuropathic symptoms (numbness, tingling) were recorded by structured questioning at both time points. Pre-dialysis blood samples were drawn from the arterial line before heparin administration. Active B12 (holotranscobalamin) was not available at this centre and was not assessed. Analysis. Data were analysed using SPSS version 27. Continuous variables are summarized as mean ± SD and median (IQR); categorical variables as frequencies and percentages. Normality was assessed with the Shapiro-Wilk test. Because most variables were non-normally distributed, between-group comparisons used the Mann-Whitney U test, and within-group pre-versus-post changes used the Wilcoxon signed-rank test. Categorical outcomes were compared using the chi-square or Fisher exact test, as appropriate. A two-sided p\<0.05 was considered statistically significant. Registration note. This trial was registered retrospectively. Enrollment and data collection were carried out under IRB approval (Institutional Review Board, Allama Iqbal Medical College / Jinnah Hospital, Lahore; reference ERB165/1/30-05-2024-S1, dated 30-05-2024) with a dated protocol specifying the primary and secondary outcomes reported here; no changes to outcomes were made after unblinding of results, as the study was open-label and non-randomized by design.