Condition category
Urological and Genital Diseases
Date applied
14/02/2012
Date assigned
17/02/2012
Last edited
03/08/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

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

Trial website

http://www.bicarb.org.uk

Contact information

Type

Scientific

Primary contact

Dr Miles Witham

ORCID ID

Contact details

Ageing and Health
Ninewells Hospital
Dundee
DD1 9SY
United Kingdom
-
m.witham@dundee.ac.uk

Type

Scientific

Additional contact

Ms Deirdre Plews

ORCID ID

Contact details

BiCARB Trial Manager
Tayside Clinical Trials Unit
Residency Block
Level 3
Ninewells Hospital & Medical School
Dundee
DD1 9SY
United Kingdom
+44 (0)1382 383 993
d.e.plews@dundee.ac.uk

Additional identifiers

EudraCT number

2011-005271-16

ClinicalTrials.gov number

Protocol/serial number

2010NE02

Study information

Scientific title

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis?

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.

On 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.

Ethics approval

East of Scotland Research Ethics Service REC 2, 16/03/2012

Study design

Randomised double-blind parallel-group placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Quality of life

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

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

Phase

Not Applicable

Drug names

Sodium bicarbonate

Primary outcome measures

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 trial start date

01/10/2012

Overall trial end date

30/09/2018

Reason abandoned

Eligibility

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 type

Patient

Age group

Senior

Gender

Both

Target number of participants

380

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

United Kingdom

Trial participating centre

Ninewells Hospital
Dundee
DD1 9SY
United Kingdom

Sponsor information

Organisation

Tayside Medical Sciences Centre (UK)

Sponsor details

Level 3 Residences
Ninewells Hospital
Dundee
DD1 9SY
United Kingdom
-
c.forde@dundee.ac.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

NIHR Health Technology Assessment (HTA) (UK) (10/71/01)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Protocol paper accepted for publication. Other to be confirmed at later date.

Intention to publish date

30/09/2018

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2015 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/26231610

Publication citations

Additional files

Editorial Notes