Effects of Oral Sodium Bicarbonate Supplementation in Haemodialysis Patients (BicHD)

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Feasibility Randomised Controlled Trial: Effects of Oral Sodium Bicarbonate Supplementation in Patients on Haemodialysis

Conditions
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End-stage Renal Disease

Intervention / Treatment
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* Drug: sodium bicarbonate 500mg capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment<br>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. | Drug: sodium bicarbonate 500mg capsules<br>* Defined by active substance and brand names not specified in protocol<br>|
| No Intervention: Control<br>Standard haemodialysis treatment thrice weekly using a standard dialysate containing bicarbonate at a concentration of 35mmols/L. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 weekly blood tests over a period of 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | 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. | 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) | 3 timepoints (weeks 4,8 and 16) over a period of 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Haemodialysis, sodium bicarbonate, potassium, arrhythmia, muscle, symptoms