Bicarbonate for Chronic Kidney Disease and Acidosis
| ISRCTN | ISRCTN09486651 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN09486651 |
| EudraCT/CTIS number | 2011-005271-16 |
| Secondary identifying numbers | 2010NE02; HTA 10/71/01 |
- Submission date
- 14/02/2012
- Registration date
- 17/02/2012
- Last edited
- 18/03/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Urological and Genital Diseases
Plain English Summary
Background and study aims
Many people with chronic kidney disease have higher than usual levels of acid in the blood. Higher levels of acid may worsen kidney function, blood vessel health and bone health, as well as stopping your muscles from working as well as they should. This in turn may make people feel tired and reduce quality of life. Acid levels can be treated with sodium bicarbonate (used in baking powder); this is used as a treatment in some people with kidney disease and high levels of acid. We do not know whether the benefits of this treatment (on muscle, bone, kidneys, blood vessels and quality of life) are greater that the potential side effects (such as raising blood pressure, fluid retention and having to take extra tablets).
We therefore aim to test whether taking daily bicarbonate tablets improves physical function, quality of life, bone and blood vessel health in patients with advanced chronic kidney disease and high levels of acid in the blood.
Who can participate?
People aged 60 and over who have advanced chronic kidney disease, but who are not on dialysis
What does the study involve?
The study takes 2 years in total to complete. The study is of randomised, double-blind design. This means that you will be asked to take medication by mouth three times a day. This will either contain bicarbonate, or a placebo (dummy) medication. The one that you will be given is decided in a random way (a bit like tossing a coin, but done by a computer). Neither you nor the research team will know which you are taking until after the study is finished. This means that the results of the study cannot be influenced by you or the researchers knowing what you are taking. Participants will receive either sodium bicarbonate or placebo (dummy tablets), starting with 1 tablet three times a day, rising to two tablets three times a day after 3 months. We will do the following tests at each study visit, which take place before the start of the study then at 3, 6, 12 and 24 months. We will measure your blood pressure while you are sitting down. We will check your height and weight. We will take a blood test (about two tablespoons of blood)). Blood samples will be stored and tested at the end of the study. We will ask you to bring a urine sample with you. You will be asked to do some mobility tests: - standing tests, balance tests, timed getting up from a chair and a test to measure your hand grip strength. You will be asked to walk up and down a corridor for six minutes at your own pace. We will measure how far you can walk in that time. We will ask you two questionnaires about your quality of life and how your kidney problems affect your quality of life.
What are the possible benefits and risks of participating?
Taking part in the trial will allow us to see if bicarbonate treatment improves the health and physical function of people with acidosis and chronic kidney disease. This dose of sodium bicarbonate is commonly used in people with kidney disease. Increase in blood pressure, fluid retention and bloating are experienced by some people, and we will be asking you about these side effects at each visit. Having blood taken can cause some bruising. The blood pressure cuff causes mild discomfort to some people.
Where is the study run from?
The study is run from the University of Dundee and centres in Aberdeen, Canterbury, Dundee, Salford, Sheffield, Preston, Portsmouth, Mid Essex, Manchester, Leicester, North Midlands, Pennine, Wolverhampton, Highland, Wirral, Sussex, Exeter, Plymouth, Southend, Fife, Gloucestershire and Birmingham (UK).
When is the study starting and how long is it expected to run for?
The study will start recruitment in July 2012. Results are anticipated to be available in June 2018; participants will be recruited for the first 18 months of the trial.
Who is funding the study?
The Health Technology Assessment board (HTA) of the National Institute for Health Research, UK
Who is the main contact?
Dr Miles D Witham
m.witham@dundee.ac.uk
Contact information
Scientific
NIHR Newcastle Biomedical Research Centre
Newcastle University
Campus for Ageing and Vitality
Newcastle
NE4 5PL
United Kingdom
 ORCID ID |
0000-0002-1967-0990 |
|---|---|
| Miles.Witham@newcastle.ac.uk |
Scientific
BiCARB Trial Manager
Tayside Clinical Trials Unit
Residency Block
Level 3
Ninewells Hospital & Medical School
Dundee
DD1 9SY
United Kingdom
| Phone | +44 (0)1382 383 993 |
|---|---|
| m.band@dundee.ac.uk |
Study information
| Study design | Randomised double-blind parallel-group placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Quality of life |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis? |
| Study acronym | BiCARB |
| Study hypothesis | To determine whether oral bicarbonate therapy improves physical function and quality of life compared to placebo in older people with Chronic Kidney disease and mild acidosis. |
| Ethics approval(s) | East of Scotland Research Ethics Service REC 2, 16/03/2012 |
| Condition | Chronic kidney disease |
| Intervention | Oral sodium bicarbonate 500 mg three times a day, rising to 1 g three times a day or matching placebo |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Sodium bicarbonate |
| Primary outcome measure | Change in Short Physical Performance Battery (SPPB) between baseline and 12 months |
| Secondary outcome measures | Current secondary outcome measures as of 10/07/2015: 1. EQ-5D 2. SPPB (baseline, 3, 6, 24 months) 3. Serum sodium, potassium, magnesium, urea, bicarbonate, calcium, phosphate, alkaline phosphatase, creatinine (eGFR calculated by MDRD4 equation), albumin, haemoglobin, thyroid function, HbA1c, lipids 4. Cystatin C 5. Urinary protein/creatinine ratio and urinary albumin/creatinine ratio 6. Height (at screening visit only), weight and anthropometric data (mid arm circumference; triceps skinfold thickness; mid thigh circumference) 7. Handgrip strength measured using dynamometry 8. Six minute walk test 9. KDQoL, a disease-specific quality of life measure 10. Office blood pressure. 3 readings will be taken; the mean of the 2nd and 3rd reading will be used as the outcome 11. Commencement on dialysis 12. All-cause mortality (via General Register Office death records) 13. Death from end-stage renal failure 14. Cardiovascular mortality 15. All hospitalisations (via hospital and GP morbidity records; including heart failure, other cardiovascular and renal-related hospitalisations) 16. Outpatients and general practitioner (GP) visits 17. Changes in medication use, with particular focus on vascular medications and phosphate binders 18. Fractures will be recorded by direct patient report, verified with GP and hospital records 19. Falls will be recorded prospectively using the validated falls diary method 20. Information on side effects (e.g. nausea, indigestion, ankle oedema) will be sought by patient self-report. Adherence to study medication will be assessed by tablet counting. 21. Bone and Vascular Secondary outcomes (measured at baseline, 12 and 24 months) 21.1. Serum markers of bone turnover: bone-specific alkaline phosphatase and tartrate-resistant acid-phosphatase 5b 21.2. Parathyroid hormone (PTH), 25-hydroxy vitamin D (25OHD) and 1,25OHD 21.3. B-type natriuretic peptide Measured at baseline, 3, 6, 12, and 24 months Previous secondary outcome measures: 1. EQ-5D 2. SPPB (baseline, 3, 6, 24 months) 3. Serum sodium, potassium, magnesium, urea, bicarbonate, calcium, phosphate, alkaline phosphatase, creatinine (eGFR calculated by MDRD4 equation), albumin, haemoglobin, thyroid function, HbA1c, lipids 4. Cystatin C 5. Urinary protein/creatinine ratio and urinary albumin/creatinine ratio 6. Height (at screening visit only), weight and anthropometric data (mid arm circumference; triceps skinfold thickness; mid thigh circumference) 7. Handgrip strength measured using dynamometry 8. Six minute walk test 9. KDQoL, a disease-specific quality of life measure 10. Office Blood pressure. 3 readings will be taken; the mean of the 2nd and 3rd reading will be used as the outcome 11. Commencement on dialysis 12. All-cause mortality (via General Register Office death records) 13. Death from end-stage renal failure 14. Cardiovascular mortality 15. All hospitalisations (via hospital and GP morbidity records; including heart failure, other cardiovascular and renal-related hospitalisations) 16. Outpatients and general practitioner (GP) visits 17. Changes in medication use, with particular focus on vascular medications and phosphate binders 18. Fractures will be recorded by direct patient report, verified with GP and hospital records 19. Falls will be recorded prospectively using the validated falls diary method 20. Information on side effects (e.g. nausea, indigestion, ankle oedema) will be sought by patient self-report. Adherence to study medication will be assessed by tablet counting. 21. Bone and Vascular substudy - Secondary outcomes (measured at baseline, 12 and 24 months) on up to 150 patients 21.1. Bone mineral density at femoral neck and forearm using DEXA. 21.2. Body composition using DEXA. 21.3. Serum markers of bone turnover: bone-specific alkaline phosphatase and tartrate-resistant acid-phosphatase 5b 21.4. Parathyroid hormone (PTH), 25-hydroxy vitamin D (25OHD) and 1,25OHD 21.5. Arterial stiffness, measured using pulse wave velocity and augmentation index 21.6. B-type natriuretic peptide Measured at baseline, 3, 6, 12, and 24 months |
| Overall study start date | 01/10/2012 |
| Overall study end date | 30/09/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Senior |
| Sex | Both |
| Target number of participants | 380 |
| Total final enrolment | 300 |
| Participant inclusion criteria | Current inclusion criteria as of 10/07/2015: 1. Participant is willing and able to give informed consent for participation in the study 2. Male or female aged 60 years or above 3. Estimated Glomerular Filtration Rate (eGFR) <30 ml/min (i.e. CKD stages 4 and 5) found at screening visit 4. Serum Bicarbonate <22 mmol/L 5. Able (in the Investigators opinion) and willing to comply with all study requirements Previous inclusion criteria: 1. Participant is willing and able to give informed consent for participation in the study 2. Male or female aged 65 years or above 3. Estimated Glomerular Filtration Rate (eGFR) <30 ml/min (i.e. CKD stages 4 and 5) found at screening visit 4. Serum Bicarbonate <22 mmol/L 5. Able (in the Investigators opinion) and willing to comply with all study requirements |
| Participant exclusion criteria | Current exclusion criteria as of 10/07/2015: 1. Severe cognitive impairment precluding written informed consent 2. Already taking bicarbonate therapy; those taking bicarbonate therapy may be included after a 3 month washout period. 3. Documented renal tubular acidosis (such patients are likely to require bicarbonate, often in very large doses) 4. On renal replacement therapy (haemodialysis or peritoneal dialysis) 5. Anticipated to start renal replacement therapy within 3 months 6. Severe cognitive impairment precluding written informed consent 7. Participant who is terminally ill, as defined as less than 3 months expected survival 8. Decompensated chronic heart failure (to ensure that fluid overload is not exacerbated by the additional sodium load from the intervention) 9. Bisphosphonate therapy (to avoid obscuring bone turnover effects; patients with CKD stages 4/5 should not usually be taking bisphosphonates as this is a listed contraindication) 10. Uncontrolled hypertension (BP>150/90 despite use of four agents) unless evidence of well controlled blood pressure e.g. 24 hour BP readings or home readings Previous exclusion criteria: 1. Severe cognitive impairment precluding written informed consent 2. Already taking bicarbonate therapy 3. Documented renal tubular acidosis (such patients are likely to require bicarbonate, often in very large doses) 4. On renal replacement therapy (haemodialysis or peritoneal dialysis) 5. Anticipated to start renal replacement therapy within 3 months 6. Severe cognitive impairment precluding written informed consent 7. Participant who is terminally ill, as defined as less than 3 months expected survival 8. Decompensated chronic heart failure (to ensure that fluid overload is not exacerbated by the additional sodium load from the intervention) 9. Bisphosphonate therapy (to avoid obscuring bone turnover effects; patients with CKD stages 4/5 should not usually be taking bisphosphonates as this is a listed contraindication) 10. Calcium carbonate use (to avoid interaction with bicarbonate) 11. Sevelamer hydrochloride use (to avoid increasing acid load) 12. Uncontrolled hypertension (BP>150/90 despite use of four agents) |
| Recruitment start date | 01/07/2012 |
| Recruitment end date | 31/03/2016 |
Locations
Countries of recruitment
- Scotland
- United Kingdom
Study participating centre
DD1 9SY
United Kingdom
Sponsor information
Hospital/treatment centre
Level 3 Residences
Ninewells Hospital
Dundee
DD1 9SY
Scotland
United Kingdom
| c.forde@dundee.ac.uk | |
"ROR" |
https://ror.org/000ywep40 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/04/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Current publication and dissemination plan as of 12/03/2020: Planned publication in a high-impact peer-reviewed journal, estimated early to mid 2020. |
| IPD sharing plan | De-identified participant level data will be available from the Chief Investigator or the Sponsor to bona-fide academic research teams, subject to submission of a proposal for data use, analysis and publication, and approval by a data-sharing committee. Previous publication and dissemination plan criteria: Planned publication in high-impact peer reviewed journal, estimated mid to late 2019. IPD sharing statement De-identified participant level data will be available from the Chief Investigator or the Sponsor to bona-fide academic research teams, subject to submission of a proposal for data use, analysis and publication, and approval by a data-sharing committee. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 01/08/2015 | Yes | No | |
| Basic results | 22/02/2019 | 22/02/2019 | No | No | |
| Results article | results | 01/12/2020 | 09/04/2020 | Yes | No |
| Basic results | 21/04/2020 | No | No | ||
| Other publications | HTA report | 01/06/2020 | 23/06/2020 | Yes | No |
| Other publications | secondary analysis of associations between frailty, physical performance, and renal biomarkers | 01/03/2021 | 18/03/2021 | Yes | No |
Additional files
- ISRCTN09486651_BasicResults_22Feb19.pdf
- Uploaded 22/02/2019
Editorial Notes
18/03/2021: Publication reference added.
23/06/2020: Publication reference added.
21/04/2020: Added clinicaltrialsregister.eu link to basic results (scientific).
09/04/2020: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
12/03/2020: The following changes have been made:
1. The intention to publish date has been changed from 30/09/2019 to 30/04/2020.
2. The publication and dissemination plan has been updated to reflect the changes above.
22/02/2019: Contact details updated, publication and dissemination plan and IPD sharing statement added. The basic results of this trial have been uploaded as an additional file.
10/07/2015: The following changes were made to the trial record:
1. The overall trial start date was changed from 01/07/2012 to 01/10/2012.
2. The overall trial end date was changed from 30/06/2016 to 30/09/2018.
