title: Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Metabolic acidosis is more common with advancing chronic kidney disease, and has been associated with impaired physical function, impaired bone health, accelerated decline in kidney function and increased vascular risk. Although oral sodium bicarbonate is widely used to correct metabolic acidosis, there exist potential risks of therapy including worsening hypertension and fluid overload. Little trial evidence exists to decide whether oral bicarbonate therapy is of net benefit in advanced chronic kidney disease, particularly in older people who are most commonly affected, and in whom physical function, quality of life and vascular health are at least as important outcomes as decline in renal function.
  
  
  METHODS
  BiCARB is a multi-centre, double-blind, placebo controlled, randomised trial evaluating the clinical and cost-effectiveness of oral sodium bicarbonate in the management of older people with chronic kidney disease and severely reduced glomerular filtration rate (GFR) who have a mild degree of metabolic acidosis. The trial will recruit 380 patients from renal, Medicine for the Elderly, and primary care services across centres in the United Kingdom. Male and female patients aged 60 years and older with an estimated glomerular filtration rate of <30 mL/min/1.73 m(2), not on dialysis, and with serum bicarbonate concentrations <22 mmol/L will be eligible for participation. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at 12 months. Secondary outcomes include muscle strength, quality of life measured using the EQ-5D score and KDQoL tools, cost effectiveness, renal function, presence of albuminuria and blood pressure. Markers of bone turnover (25-hydroxyvitamin D, 1,25-hydroxyvitamin D, tartrate-resistant acid phosphatase-5b and bone-specific alkaline phosphatase) and vascular health (B-type natriuretic peptide) will be measured. Participants will receive a total of 24 months of either bicarbonate or placebo. The results will provide the first robust test of the overall clinical and cost-effectiveness of this commonly used therapy in older patients with severely reduced kidney function.
  
  
  BACKGROUND
  www.isrctn.com; ISRCTN09486651, registered 17 February 2012.
authors.affiliation: Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee, DD1 9SY, UK. m.witham@dundee.ac.uk.
authors.forename: Miles D
authors.initials: MD
authors.lastname: Witham
authors.affiliation: Tayside Clinical Trials Unit, University of Dundee / NHS Tayside, Dundee, UK. m.band@dundee.ac.uk.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Band
authors.affiliation: Tayside Clinical Trials Unit, University of Dundee / NHS Tayside, Dundee, UK. r.littleford@dundee.ac.uk.
authors.forename: Roberta C
authors.initials: RC
authors.lastname: Littleford
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK. a.avenell@abdn.ac.uk.
authors.forename: Alison
authors.initials: A
authors.lastname: Avenell
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK. r.l.soiza@abdn.ac.uk.
authors.forename: Roy L
authors.initials: RL
authors.lastname: Soiza
authors.affiliation: Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee, DD1 9SY, UK. m.e.t.mcmurdo@dundee.ac.uk.
authors.forename: Marion E T
authors.initials: ME
authors.lastname: McMurdo
authors.affiliation: Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee, DD1 9SY, UK. d.sumukadas@dundee.ac.uk.
authors.forename: Deepa
authors.initials: D
authors.lastname: Sumukadas
authors.affiliation: Epidemiology and Biostatistics Unit, University of Dundee, Dundee, UK. s.a.ogston@dundee.ac.uk.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Ogston
authors.affiliation: Department of Clinical Biochemistry, East Kent NHS Trust, Canterbury, UK. elamb@nhs.net.
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Lamb
authors.affiliation: Department of Chemical Pathology, Guy's and St Thomas' Hospitals, London, UK. geeta.hampson@kcl.ac.uk.
authors.forename: Geeta
authors.initials: G
authors.lastname: Hampson
authors.affiliation: Health Economics Research Unit, University of Aberdeen, Aberdeen, UK. p.mcnamee@abdn.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: McNamee
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects*; D000138:Acidosis / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology / Q000523:psychology; D000284:Administration, Oral; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D016527:Drug Costs; D005260:Female; D005919:Glomerular Filtration Rate; D006304:Health Status; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D053580:Muscle Strength; D011788:Quality of Life; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000175:diagnosis / Q000191:economics / Q000503:physiopathology / Q000523:psychology; D012107:Research Design; D012720:Severity of Illness Index; D017693:Sodium Bicarbonate / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D015415:Biomarkers; D017693:Sodium Bicarbonate