TY - JOUR
T1 - Clinical and cost-effectiveness of oral sodium bicarbonate therapy for older patients with chronic kidney disease and low-grade acidosis
T2 - A pragmatic randomised, double-blind, placebo-controlled trial
AU - Witham, Miles D.
AU - Band, Margaret
AU - Ahmed, Aimun K.
AU - Almond, Michael K.
AU - Balasubramaniam, Gowrie S.
AU - Basnayake, Kolitha
AU - Sumukadas, Deepa
AU - Chan, Anthony
AU - Chong, Huey Yi
AU - Donnan, Peter T.
AU - Duncan, Neill
AU - Hampson, Greeta
AU - Hu, May Khei
AU - Kalra, Philip
AU - Kennedy, Gwen
AU - Kirk, Adam
AU - Lamb, Edmund
AU - Lambie, Stewart
AU - Littleford, Roberta
AU - McNamee, Paul
AU - Mishra, Biswa
AU - Mitra, Sandip
AU - Nicholas, Johann
AU - Plews, Deirdre
AU - Rauchhaus, Petra
AU - Soiza, Roy L.
AU - Stevens, Paul E.
AU - Sumukadas, Deepa
AU - Tse, Wai
AU - Warwick, Graham
AU - Wilkie, Martin
AU - Winnett, Georgia
AU - Avenell, Alison
N1 - Funding: National Institute for Health Research Health Technology Assessment programme (reference 10/71/01). Acknowledgements We would like to acknowledge the support received via the NHS Scotland Support for Science scheme; the NIHR Renal and Ageing Comprehensive Research Networks; the work of all of the research nurses and study teams at sites, Tayside Clinical Trials Unit staff, and most importantly all those with kidney disease who participated in the trial. In addition, we acknowledge the support and advice we received from the independent Trial Steering Committee members (Professor David Stott, Professor Patrick Mark, Professor Tahir Masud and Mr Alex Stephen) and the independent Data Monitoring Committee (Professor Alex McConnachie, Professor David Wheeler, Dr Nicosha de Souza, Dr Andrew Clegg). We also acknowledge the efforts of all the site Investigators, research nurses and support teams.
PY - 2020/4/9
Y1 - 2020/4/9
N2 - BACKGROUND: Chronic kidney disease with metabolic acidosis is common in older people, but the effectiveness of oral sodium bicarbonate therapy in this group is unclear. We tested whether oral sodium bicarbonate provides net health benefit for older people with advanced chronic kidney disease and serum bicarbonate concentrations < 22 mmol/L.METHODS: Pragmatic multicentre, parallel group, double-blind, placebo-controlled randomised trial. We recruited adults aged ≥ 60 years with estimated glomerular filtration rate of < 30 mL/min/1.73 m
2, not receiving dialysis, with serum bicarbonate concentration < 22 mmol/L, from 27 nephrology and geriatric medicine departments in the UK. Participants received oral sodium bicarbonate (up to 3 g/day) or matching placebo given for up to 2 years, randomised in a 1:1 ratio. The primary outcome was between-group difference in the Short Physical Performance Battery (SPPB) at 12 months, adjusted for baseline values, analysed by intention to treat. Secondary outcomes included generic and disease-specific quality of life (EQ-5D and KDQoL tools), anthropometry, renal function, walk distance, blood pressure, bone and vascular health markers, and incremental cost per quality-adjusted life year gained.
RESULTS: We randomised 300 participants between May 2013 and February 2017, mean age 74 years, 86 (29%) female. At 12 months, 116/152 (76%) participants allocated to bicarbonate and 104/148 (70%) allocated to placebo were assessed; primary outcome data were available for 187 participants. We found no significant treatment effect for the SPPB: bicarbonate arm 8.3 (SD 2.5) points, placebo arm 8.8 (SD 2.2) and adjusted treatment effect - 0.4 (95% CI - 0.9 to 0.1, p = 0.15). We found no significant treatment effect for glomerular filtration rate (0.6 mL/min/1.73 m
2, 95% CI - 0.8 to 2.0, p = 0.39). The bicarbonate arm showed higher costs and lower quality of life as measured by the EQ-5D-3L tool over 1 year (£564 [95% CI £88 to £1154]); placebo dominated bicarbonate under all sensitivity analyses. Adverse events were more frequent in those randomised to bicarbonate (457 versus 400).
CONCLUSIONS: Oral sodium bicarbonate did not improve physical function or renal function, increased adverse events and is unlikely to be cost-effective for use by the UK NHS for this patient group.TRIAL REGISTRATION: European Clinical Trials Database (2011-005271-16) and ISRCTN09486651; registered 17 February 2012.
AB - BACKGROUND: Chronic kidney disease with metabolic acidosis is common in older people, but the effectiveness of oral sodium bicarbonate therapy in this group is unclear. We tested whether oral sodium bicarbonate provides net health benefit for older people with advanced chronic kidney disease and serum bicarbonate concentrations < 22 mmol/L.METHODS: Pragmatic multicentre, parallel group, double-blind, placebo-controlled randomised trial. We recruited adults aged ≥ 60 years with estimated glomerular filtration rate of < 30 mL/min/1.73 m
2, not receiving dialysis, with serum bicarbonate concentration < 22 mmol/L, from 27 nephrology and geriatric medicine departments in the UK. Participants received oral sodium bicarbonate (up to 3 g/day) or matching placebo given for up to 2 years, randomised in a 1:1 ratio. The primary outcome was between-group difference in the Short Physical Performance Battery (SPPB) at 12 months, adjusted for baseline values, analysed by intention to treat. Secondary outcomes included generic and disease-specific quality of life (EQ-5D and KDQoL tools), anthropometry, renal function, walk distance, blood pressure, bone and vascular health markers, and incremental cost per quality-adjusted life year gained.
RESULTS: We randomised 300 participants between May 2013 and February 2017, mean age 74 years, 86 (29%) female. At 12 months, 116/152 (76%) participants allocated to bicarbonate and 104/148 (70%) allocated to placebo were assessed; primary outcome data were available for 187 participants. We found no significant treatment effect for the SPPB: bicarbonate arm 8.3 (SD 2.5) points, placebo arm 8.8 (SD 2.2) and adjusted treatment effect - 0.4 (95% CI - 0.9 to 0.1, p = 0.15). We found no significant treatment effect for glomerular filtration rate (0.6 mL/min/1.73 m
2, 95% CI - 0.8 to 2.0, p = 0.39). The bicarbonate arm showed higher costs and lower quality of life as measured by the EQ-5D-3L tool over 1 year (£564 [95% CI £88 to £1154]); placebo dominated bicarbonate under all sensitivity analyses. Adverse events were more frequent in those randomised to bicarbonate (457 versus 400).
CONCLUSIONS: Oral sodium bicarbonate did not improve physical function or renal function, increased adverse events and is unlikely to be cost-effective for use by the UK NHS for this patient group.TRIAL REGISTRATION: European Clinical Trials Database (2011-005271-16) and ISRCTN09486651; registered 17 February 2012.
KW - sodium bicarbonate
KW - renal insufficiency
KW - chronic
KW - acidosis
KW - randomised controlled trial
UR - http://www.scopus.com/inward/record.url?scp=85083272904&partnerID=8YFLogxK
U2 - 10.1186/s12916-020-01542-9
DO - 10.1186/s12916-020-01542-9
M3 - Article
C2 - 32268897
SN - 1366-5278
VL - 18
JO - Health Technology Assessment
JF - Health Technology Assessment
M1 - 91 (2020)
ER -