End-stage Renal DiseasePhase 4BicHDNCT02692378
Effects of Oral Sodium Bicarbonate Supplementation in Haemodialysis Patients (BicHD)
A Phase 4 study testing sodium bicarbonate 500mg capsules in people with End-stage Renal Disease, run by Imperial College Healthcare NHS Trust at 1 site in United Kingdom.
Trial summary
The purpose of the study is to investigate whether oral sodium bicarbonate supplementation to ensure a constant bicarbonate profile in haemodialysis patients will primarily lower predialysis potassium levels and secondary lead to improvements in cardiac function, muscle mass and dialysis related symptoms. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- End-stage Renal Disease
- What is being tested?
- sodium bicarbonate 500mg capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2015to May 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients on haemodialysis for at least 3 months, Patients who primarily have predialysis bicarbonate levels of less than 22mmols/L over the last 6 months, Patients who are not already taking oral sodium bicarbonate, Able and willing to provide written informed consent
Who cannot join
- Patients who primarily have predialysis potassium levels of less than 4mmols/L over the last 6 months, Patients who are already taking oral sodium bicarbonate, Patients on lithium, Bedbound patients, Pregnant patients, Dementia, Recurrent hospital admissions, Non-English speaking and unable to provide written informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Feasibility Randomised Controlled Trial: Effects of Oral Sodium Bicarbonate Supplementation in Patients on Haemodialysis
The purpose of the study is to investigate whether oral sodium bicarbonate supplementation to ensure a constant bicarbonate profile in haemodialysis patients will primarily lower predialysis potassium levels and secondary lead to improvements in cardiac function, muscle mass and dialysis related symptoms.
Read the detailed description
Background:
One of the functions of dialysis is to correct electrolyte abnormalities which occur with renal failure, such as variations in potassium and bicarbonate levels, which are linked to important clinical outcomes for patients. Metabolic acidosis, reflected by falling bicarbonate levels, is a frequent event in haemodialysis patients and its correction is one of the goals of effective dialysis. Bicarbonate replacement is routinely delivered during each dialysis session thrice weekly with the use of high dialysate bicarbonate. However, local and national data show that over 50% of patients fail to meet a bicarbonate level within the normal range before each dialysis session. Low predialysis bicarbonate levels of less than 22mmols/L have been linked with increased all-cause mortality in haemodialysis patients.
Evidence from previous studies suggests that a continuous replacement (i.e. daily) with oral sodium bicarbonate capsules may be a superior correction of acidosis to the current treatment of intermittent replacement during dialysis.
Aims and objectives:
This randomised controlled study aims to investigate the effects of oral sodium bicarbonate supplementation on:
Primary objective: Pre and post dialysis potassium without increasing intradialytic potassium gradient.
Secondary objectives:
- Risk of arrhythmia as measured by ECG analysis
- Muscle mass as measured by body composition monitoring
- Muscle function as measured by handgrip strength
- Haemodialysis related cramps as measured by a symptom scale-renal questionnaire
Patients will be recruited from Imperial College Healthcare NHS (National Heath Service) Trust haemodialysis units and randomised to two equally numbered groups. One group will receive the standard dialysis treatment (control) and the other one will receive the standard dialysis with the addition of capsules of sodium bicarbonate (intervention). The dose of sodium bicarbonate will be adjusted according to individual levels. The study duration is 16 weeks.
- Conditions
- End-stage Renal Disease
- Being tested
- sodium bicarbonate 500mg capsules
- Keywords
- Haemodialysis, sodium bicarbonate, potassium, arrhythmia, muscle, symptoms
- Medical subject headings
- Kidney Failure, Chronic, Arrhythmias, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sodium bicarbonate 500mg capsulesDrug
Defined by active substance and brand names not specified in protocol
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Active comparator | Standard haemodialysis treatment thrice weekly (using a standard dialysate containing bicarbonate at a concentration of 35mmols/L) with the addition of oral sodium bicarbonate 500mg capsules for 12 weeks (weeks 5-16 of the study).
The dosage will be titrated to individual blood levels. Starting dose will be 1g twice daily and if predialysis bicarbonate levels remain <22mmols/L the dose will be increased by 0.5g twice daily each week. The maximum dose would be 3g twice daily.
The oral sodium bicarbonate may be withheld on dialysis days, when bicarbonate will be supplemented through the dialysate. This will be assessed on a case by case basis. Receives: Drug: sodium bicarbonate 500mg capsules |
| Control | No intervention | Standard haemodialysis treatment thrice weekly using a standard dialysate containing bicarbonate at a concentration of 35mmols/L. |
What is being measured
The primary outcome is the main question the study is designed to answer.
pre dialysis potassium level and intradialytic potassium gradient
Measurements over the first 4 weeks to establish blood potassium profile. Measurements over weeks 5-8 to detect early blood changes. Measurement over weeks 13-16 to detect late blood changes.
Measured: 12 weekly blood tests over a period of 16 weeks
Secondary outcomes (4)
12 lead Electrocardiogram analysis
Electrocardiogram analysis before and after dialysis for the measurement of QT dispersion. Increase of the QT dispersion is linked to risk of ventricular arrhythmias.
Measured: 3 timepoints (weeks 4, 8 and 16) over a period of 16 weeks
Total body muscle mass
Body composition measurement before dialysis with the validated body composition monitor by Fresenius
Measured: 2 timepoints (weeks 4 and 16) over a period of 16 weeks
Handgrip strength
Handgrip strength to measure muscle function. Measured before dialysis with the ®Jamar handgrip dynamometer.
Measured: 2 timepoints (weeks 4 and 16) over a period of 16 weeks
Symptom severity
Haemodialysis related symptoms measured by a validated palliative outcome symptom scale-renal questionnaire (POS-S)
Measured: 3 timepoints (weeks 4,8 and 16) over a period of 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2016 (estimated)
- Study startNov 2015
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for End-stage Renal DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College Healthcare NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom
- Responsible party
- Sponsor
- Investigators
- Damien Ashby, PhD, MRCP, Principal investigator, Imperial College Healthcare NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02692378
- Sponsor's protocol ID
- 15HH2613
- Acronym
- BicHD
- Status last verified
- Nov 2015
- First submitted
- 23 Feb 2016
- Last updated
- 3 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Bleyer AJ, Russell GB, Satko SG. Sudden and cardiac death rates in hemodialysis patients. Kidney Int. 1999 Apr;55(4):1553-9. doi: 10.1046/j.1523-1755.1999.00391.x.
PubMed 10201022Bossola M, Giungi S, Tazza L, Luciani G. Long-term oral sodium bicarbonate supplementation does not improve serum albumin levels in hemodialysis patients. Nephron Clin Pract. 2007;106(1):c51-6. doi: 10.1159/000101484. Epub 2007 Apr 2.
PubMed 17409769Brady JP, Hasbargen JA. Correction of metabolic acidosis and its effect on albumin in chronic hemodialysis patients. Am J Kidney Dis. 1998 Jan;31(1):35-40. doi: 10.1053/ajkd.1998.v31.pm9428449.
PubMed 9428449Brass EP, Adler S, Sietsema KE, Amato A, Esler A, Hiatt WR. Peripheral arterial disease is not associated with an increased prevalence of intradialytic cramps in patients on maintenance hemodialysis. Am J Nephrol. 2002 Sep-Dec;22(5-6):491-6. doi: 10.1159/000065285.
PubMed 12381949Cupisti A, Galetta F, Caprioli R, Morelli E, Tintori GC, Franzoni F, Lippi A, Meola M, Rindi P, Barsotti G. Potassium removal increases the QTc interval dispersion during hemodialysis. Nephron. 1999 Jun;82(2):122-6. doi: 10.1159/000045387.
PubMed 10364703Graham KA, Reaich D, Channon SM, Downie S, Goodship TH. Correction of acidosis in hemodialysis decreases whole-body protein degradation. J Am Soc Nephrol. 1997 Apr;8(4):632-7. doi: 10.1681/ASN.V84632.
PubMed 10495793Heguilen RM, Sciurano C, Bellusci AD, Fried P, Mittelman G, Rosa Diez G, Bernasconi AR. The faster potassium-lowering effect of high dialysate bicarbonate concentrations in chronic haemodialysis patients. Nephrol Dial Transplant. 2005 Mar;20(3):591-7. doi: 10.1093/ndt/gfh661. Epub 2005 Feb 1.
PubMed 15687112Ikizler TA, Pupim LB, Brouillette JR, Levenhagen DK, Farmer K, Hakim RM, Flakoll PJ. Hemodialysis stimulates muscle and whole body protein loss and alters substrate oxidation. Am J Physiol Endocrinol Metab. 2002 Jan;282(1):E107-16. doi: 10.1152/ajpendo.2002.282.1.E107.
PubMed 11739090Movilli E, Viola BF, Camerini C, Mazzola G, Cancarini GC. Correction of metabolic acidosis on serum albumin and protein catabolism in hemodialysis patients. J Ren Nutr. 2009 Mar;19(2):172-7. doi: 10.1053/j.jrn.2008.08.012.
PubMed 19218045Vashistha T, Kalantar-Zadeh K, Molnar MZ, Torlen K, Mehrotra R. Dialysis modality and correction of uremic metabolic acidosis: relationship with all-cause and cause-specific mortality. Clin J Am Soc Nephrol. 2013 Feb;8(2):254-64. doi: 10.2215/CJN.05780612. Epub 2012 Nov 26.
PubMed 23184567
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Feasibility Randomised Controlled Trial: Effects of Oral Sodium Bicarbonate Supplementation in Patients on Haemodialysis
- ClinicalTrials.gov ID
- NCT02692378
- Acronym / sponsor ID
- BicHD / 15HH2613
- Conditions
- End-stage Renal Disease
- Keywords
- Haemodialysis, sodium bicarbonate, potassium, arrhythmia, muscle, symptoms
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Imperial College Healthcare NHS TrustUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom
- Study start
- Nov 2015
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 26 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to investigate whether oral sodium bicarbonate supplementation to ensure a constant bicarbonate profile in haemodialysis patients will primarily lower predialysis potassium levels and secondary lead to improvements in cardiac function, muscle mass and dialysis related symptoms.
Detailed description
Background:
One of the functions of dialysis is to correct electrolyte abnormalities which occur with renal failure, such as variations in potassium and bicarbonate levels, which are linked to important clinical outcomes for patients. Metabolic acidosis, reflected by falling bicarbonate levels, is a frequent event in haemodialysis patients and its correction is one of the goals of effective dialysis. Bicarbonate replacement is routinely delivered during each dialysis session thrice weekly with the use of high dialysate bicarbonate. However, local and national data show that over 50% of patients fail to meet a bicarbonate level within the normal range before each dialysis session. Low predialysis bicarbonate levels of less than 22mmols/L have been linked with increased all-cause mortality in haemodialysis patients.
Evidence from previous studies suggests that a continuous replacement (i.e. daily) with oral sodium bicarbonate capsules may be a superior correction of acidosis to the current treatment of intermittent replacement during dialysis.
Aims and objectives:
This randomised controlled study aims to investigate the effects of oral sodium bicarbonate supplementation on:
Primary objective: Pre and post dialysis potassium without increasing intradialytic potassium gradient.
Secondary objectives:
- Risk of arrhythmia as measured by ECG analysis
- Muscle mass as measured by body composition monitoring
- Muscle function as measured by handgrip strength
- Haemodialysis related cramps as measured by a symptom scale-renal questionnaire
Patients will be recruited from Imperial College Healthcare NHS (National Heath Service) Trust haemodialysis units and randomised to two equally numbered groups. One group will receive the standard dialysis treatment (control) and the other one will receive the standard dialysis with the addition of capsules of sodium bicarbonate (intervention). The dose of sodium bicarbonate will be adjusted according to individual levels. The study duration is 16 weeks.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Active comparator | Drug: sodium bicarbonate 500mg capsulesStandard haemodialysis treatment thrice weekly (using a standard dialysate containing bicarbonate at a concentration of 35mmols/L) with the addition of oral sodium bicarbonate 500mg capsules for 12 weeks (weeks 5-16 of the study). The dosage will be titrated to individual blood levels. Starting dose will be 1g twice daily and if predialysis bicarbonate levels remain <22mmols/L the dose will be increased by 0.5g twice daily each week. The maximum dose would be 3g twice daily. The oral sodium bicarbonate may be withheld on dialysis days, when bicarbonate will be supplemented through the dialysate. This will be assessed on a case by case basis. |
| Control | No intervention | –Standard haemodialysis treatment thrice weekly using a standard dialysate containing bicarbonate at a concentration of 35mmols/L. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients on haemodialysis for at least 3 months, Patients who primarily have predialysis bicarbonate levels of less than 22mmols/L over the last 6 months, Patients who are not already taking oral sodium bicarbonate, Able and willing to provide written informed consent
Key exclusion criteria (1 listed)
- Patients who primarily have predialysis potassium levels of less than 4mmols/L over the last 6 months, Patients who are already taking oral sodium bicarbonate, Patients on lithium, Bedbound patients, Pregnant patients, Dementia, Recurrent hospital admissions, Non-English speaking and unable to provide written informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sodium bicarbonate 500mg capsulesDefined by active substance and brand names not specified in protocol | Drug | Treatment |
Primary outcome
pre dialysis potassium level and intradialytic potassium gradient
Time frame: 12 weekly blood tests over a period of 16 weeks
Measurements over the first 4 weeks to establish blood potassium profile. Measurements over weeks 5-8 to detect early blood changes. Measurement over weeks 13-16 to detect late blood changes.
4 secondary outcomes
12 lead Electrocardiogram analysis
Time frame: 3 timepoints (weeks 4, 8 and 16) over a period of 16 weeks
Total body muscle mass
Time frame: 2 timepoints (weeks 4 and 16) over a period of 16 weeks
Handgrip strength
Time frame: 2 timepoints (weeks 4 and 16) over a period of 16 weeks
Symptom severity
Time frame: 3 timepoints (weeks 4,8 and 16) over a period of 16 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2016.
- Background: PubMed 10201022Bleyer AJ, Russell GB, Satko SG. Sudden and cardiac death rates in hemodialysis patients. Kidney Int. 1999 Apr;55(4):1553-9. doi: 10.1046/j.1523-1755.1999.00391.x.
- Background: PubMed 17409769Bossola M, Giungi S, Tazza L, Luciani G. Long-term oral sodium bicarbonate supplementation does not improve serum albumin levels in hemodialysis patients. Nephron Clin Pract. 2007;106(1):c51-6. doi: 10.1159/000101484. Epub 2007 Apr 2.
- Background: PubMed 9428449Brady JP, Hasbargen JA. Correction of metabolic acidosis and its effect on albumin in chronic hemodialysis patients. Am J Kidney Dis. 1998 Jan;31(1):35-40. doi: 10.1053/ajkd.1998.v31.pm9428449.
- Background: PubMed 12381949Brass EP, Adler S, Sietsema KE, Amato A, Esler A, Hiatt WR. Peripheral arterial disease is not associated with an increased prevalence of intradialytic cramps in patients on maintenance hemodialysis. Am J Nephrol. 2002 Sep-Dec;22(5-6):491-6. doi: 10.1159/000065285.
- Background: PubMed 10364703Cupisti A, Galetta F, Caprioli R, Morelli E, Tintori GC, Franzoni F, Lippi A, Meola M, Rindi P, Barsotti G. Potassium removal increases the QTc interval dispersion during hemodialysis. Nephron. 1999 Jun;82(2):122-6. doi: 10.1159/000045387.
- Background: PubMed 10495793Graham KA, Reaich D, Channon SM, Downie S, Goodship TH. Correction of acidosis in hemodialysis decreases whole-body protein degradation. J Am Soc Nephrol. 1997 Apr;8(4):632-7. doi: 10.1681/ASN.V84632.
- Background: PubMed 15687112Heguilen RM, Sciurano C, Bellusci AD, Fried P, Mittelman G, Rosa Diez G, Bernasconi AR. The faster potassium-lowering effect of high dialysate bicarbonate concentrations in chronic haemodialysis patients. Nephrol Dial Transplant. 2005 Mar;20(3):591-7. doi: 10.1093/ndt/gfh661. Epub 2005 Feb 1.
- Background: PubMed 11739090Ikizler TA, Pupim LB, Brouillette JR, Levenhagen DK, Farmer K, Hakim RM, Flakoll PJ. Hemodialysis stimulates muscle and whole body protein loss and alters substrate oxidation. Am J Physiol Endocrinol Metab. 2002 Jan;282(1):E107-16. doi: 10.1152/ajpendo.2002.282.1.E107.
- Background: PubMed 19218045Movilli E, Viola BF, Camerini C, Mazzola G, Cancarini GC. Correction of metabolic acidosis on serum albumin and protein catabolism in hemodialysis patients. J Ren Nutr. 2009 Mar;19(2):172-7. doi: 10.1053/j.jrn.2008.08.012.
- Background: PubMed 23184567Vashistha T, Kalantar-Zadeh K, Molnar MZ, Torlen K, Mehrotra R. Dialysis modality and correction of uremic metabolic acidosis: relationship with all-cause and cause-specific mortality. Clin J Am Soc Nephrol. 2013 Feb;8(2):254-64. doi: 10.2215/CJN.05780612. Epub 2012 Nov 26.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Damien Ashby, PhD, MRCP principal investigator
Imperial College Healthcare NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing sodium bicarbonate 500mg capsules in people with End-stage Renal Disease, run by Imperial College Healthcare NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pre dialysis potassium level and intradialytic potassium gradient (time frame: 12 weekly blood tests over a period of 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02692378, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2016.