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

Miles D. Witham (Corresponding Author), Margaret Band, Huey Yi Chong, Peter T. Donnan, Greeta Hampson, May Khei Hu, Roberta Littleford, Edmund Lamb, Philip Kalra, Gwen Kennedy, Paul McNamee, Deirdre Plews, Petra Rauchhaus, Roy L. Soiza, Deepa Sumukadas, Graham Warwick, Alison Avenell

Research output: Contribution to journalArticle

Abstract

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
Original languageEnglish
JournalHealth Technology Assessment
Publication statusAccepted/In press - 4 Sep 2019

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Sodium Bicarbonate
Bicarbonates
Acidosis
Chronic Renal Insufficiency
Cost-Benefit Analysis
Randomized Controlled Trials
Placebos
Costs and Cost Analysis
Therapeutics
Quality of Life
Health
Renal Replacement Therapy
Quality-Adjusted Life Years
Bone Remodeling
Serum
Economics
Outcome Assessment (Health Care)
Kidney
Anthropometry
Nephrology

Keywords

  • sodium bicarbonate
  • renal insufficiency
  • chronic
  • acidosis
  • randomised controlled trial

Cite this

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. / Witham, Miles D. (Corresponding Author); Band, Margaret; Chong, Huey Yi; Donnan, Peter T.; Hampson, Greeta; Hu, May Khei; Littleford, Roberta; Lamb, Edmund; Kalra, Philip; Kennedy, Gwen; McNamee, Paul; Plews, Deirdre; Rauchhaus, Petra; Soiza, Roy L.; Sumukadas, Deepa; Warwick, Graham; Avenell, Alison.

In: Health Technology Assessment, 04.09.2019.

Research output: Contribution to journalArticle

Witham, Miles D. ; Band, Margaret ; Chong, Huey Yi ; Donnan, Peter T. ; Hampson, Greeta ; Hu, May Khei ; Littleford, Roberta ; Lamb, Edmund ; Kalra, Philip ; Kennedy, Gwen ; McNamee, Paul ; Plews, Deirdre ; Rauchhaus, Petra ; Soiza, Roy L. ; Sumukadas, Deepa ; Warwick, Graham ; Avenell, Alison. / 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. In: Health Technology Assessment. 2019.
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abstract = "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",
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author = "Witham, {Miles D.} and Margaret Band and Chong, {Huey Yi} and Donnan, {Peter T.} and Greeta Hampson and Hu, {May Khei} and Roberta Littleford and Edmund Lamb and Philip Kalra and Gwen Kennedy and Paul McNamee and Deirdre Plews and Petra Rauchhaus and Soiza, {Roy L.} and Deepa Sumukadas and Graham Warwick and Alison Avenell",
note = "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.",
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TY - JOUR

T1 - Clinical and cost-effectiveness of oral sodium bicarbonate therapy for older patients with chronic kidney disease and low-grade acidosis

T2 - The BiCARB randomised controlled trial

AU - Witham, Miles D.

AU - Band, Margaret

AU - Chong, Huey Yi

AU - Donnan, Peter T.

AU - Hampson, Greeta

AU - Hu, May Khei

AU - Littleford, Roberta

AU - Lamb, Edmund

AU - Kalra, Philip

AU - Kennedy, Gwen

AU - McNamee, Paul

AU - Plews, Deirdre

AU - Rauchhaus, Petra

AU - Soiza, Roy L.

AU - Sumukadas, Deepa

AU - Warwick, Graham

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 - 2019/9/4

Y1 - 2019/9/4

N2 - 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

AB - 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

KW - sodium bicarbonate

KW - renal insufficiency

KW - chronic

KW - acidosis

KW - randomised controlled trial

M3 - Article

JO - Health Technology Assessment

JF - Health Technology Assessment

SN - 1366-5278

ER -