Clinical and cost-effectiveness of oral sodium bicarbonate therapy for older patients with chronic kidney disease and low-grade acidosis: The BiCARB randomised controlled trial

Background: Advanced chronic kidney disease is common in older people, and is frequently accompanied by metabolic acidosis. Oral sodium bicarbonate is used to treat this acidosis, but evidence is lacking on whether this provides a net gain in health or quality of life for older people. Objectives: To determine whether oral bicarbonate therapy improves physical function, quality of life, markers of renal function, bone turnover and vascular health compared to placebo in older people with chronic kidney disease and mild acidosis, to assess the safety of oral bicarbonate, and to establish whether oral bicarbonate therapy is cost-effective in this setting. Design: Parallel group, double-blind, placebo-controlled randomised trial. Setting: Nephrology and geriatric medicine outpatient departments in 27 UK hospitals Participants: Adults aged 60 years and over with advanced chronic kidney disease (glomerular filtration rate category 4 or 5, not on dialysis), with serum bicarbonate concentrations <22 mmol/L. Interventions: Eligible participants were randomised 1:1 to oral sodium bicarbonate or matching placebo. Dosing started at 500 mg thrice daily, increased to 1 g thrice daily if serum bicarbonate concentrations were <22 mmol/L at three months. Main outcome measures: The primary outcome was the between-group difference in the Short Physical Performance Battery at 12 months, adjusted for baseline. Other outcome measures included generic and disease-specific health-related quality of life, anthropometry, six-minute walk speed, grip strength, renal function, markers of bone turnover, blood pressure and B-type natriuretic peptide. All adverse events were recorded, including commencement of renal replacement therapy. For the health economic analysis, the incremental cost per quality-adjusted life year was the main outcome. Results: 300 participants were randomised, 152 to bicarbonate and 148 to placebo. The mean age was 74 years and 86 (29%) were female. Adherence to study medication was 73% in both groups. 220 (73%) of participants were assessed at the 12 month visit. No significant treatment effect was evident for the Short Physical Performance Battery at 12 months (-0.4 points; 95%CI -0.9 to 0.1, p=0.15). No significant treatment benefit was seen for any of the secondary outcomes. Adverse events were more frequent in the bicarbonate arm (457 versus 400). Time to commencing renal replacement therapy was similar in both groups (HR 1.22, 95% CI 0.74 to 2.02, p=0.43). Health economic analysis showed higher costs and lower quality of life in the bicarbonate arm at one year with additional costs of £564 (95% CI £88 to 1154) and quality-adjusted life years difference of -0.05 (95% CI -0.08 to -0.01); placebo dominated bicarbonate under all sensitivity analyses for incremental cost-effectiveness. Limitations: The trial population was predominantly white and male, limiting generalisability. The increment in serum bicarbonate concentrations achieved was small, and benefit from larger doses of bicarbonate cannot be excluded. Future work: Once other current trials of bicarbonate therapy in chronic kidney disease are complete, an individual-participant meta-analysis would be helpful to delineate any subgroups or treatment regimens more likely to give benefit. Conclusions: Oral sodium bicarbonate did not improve a range of health measures in people aged 60 and over with chronic kidney disease category 4 or 5 and mild acidosis, and is unlikely to be cost-effective for use in the NHS in this patient group. Trial registration: ISRCTN09486651. European Clinical Trials Database (EudraCT) number 2011-005271-16