Sodium citrate versus sodium bicarbonate for increased acidity (metabolic acidosis) in patients with chronic kidney disease
| ISRCTN | ISRCTN16429332 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16429332 |
| Secondary identifying numbers | 59531 |
- Submission date
- 21/09/2021
- Registration date
- 22/09/2021
- Last edited
- 05/10/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Urological and Genital Diseases
Plain English Summary
Background and study aims
The buildup of acid in the body due to kidney disease or kidney failure is called metabolic acidosis. When your body fluids contain too much acid, it means that your body is either not getting rid of enough acid, is making too much acid, or cannot balance the acid in your body.
Metabolic acidosis is a common complication of chronic kidney disease (CKD). It means a build up of hydrogen ions with a low level of bicarbonate. This retention of hydrogen ions happens from early stages of CKD, when bicarbonate level is normal and later on it translates into metabolic acidosis. This and can cause cardiovascular and bone mineral disorders, but also CKD progression through interstitial inflammation and fibrosis.
Alkali therapy with sodium bicarbonate or citrate on top of alkali-rich diet (low animal protein or enriched in fruits and vegetable diets) it can help to raise serum bicarbonate level and thus slowing CKD progression. It was also demonstrated that alkali therapy is well tolerated, with few to no adverse events.
Current clinical practical guidelines recommend correcting the serum bicarbonate to >22 mEq/l by oral bicarbonate supplementation to maintain serum bicarbonate within the normal range (22-26 mEq/l) and although data support the hypothesis that alkali therapy preserves kidney function in patients with CKD, evidence from large-scale clinical trials is still necessary before definitive conclusions can be drawn. Moreover, to our knowledge there is no clinical trial comparing sodium citrate with sodium bicarbonate for metabolic acidosis in chronic kidney disease.
Who can participate?
Adult patients with diagnosis of metabolic acidosis and chronic kidney disease
What does the study involve?
Patients will be assigned to one of the two treatment groups.
Group 1 will receive sodium bicarbonate capsules
Group 2 will receive sodium citrate solution
Clinical and laboratory measurements will be performed monthly for a year; certain laboratory measurements will be done at 1 mo and at 12th mo.
What are the possible benefits and risks of participating?
All participants will have the opportunity to receive a detailed general evaluation and possible benefits regarding weight loss. There are the normal possible side effects of both treatments.
Where is the study run from?
Fundeni Clinical Institute (Romania)
When is the study starting and how long is it expected to run for?
Septemeber 2021 to January 2024
Who is funding the study?
Fundeni Clinical Institute (Romania)
Who is the main contact?
Dr. Gener Ismail
gener.ismail@umfcd.ro
Contact information
Scientific
18 Aleea Sinaia
Bucharest
022765
Romania
| Phone | +40(0)722792429 |
|---|---|
| gener.ismail@umfcd.ro |
Study information
| Study design | Parallel-design randomized controlled 1:1 trial single center |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | 40456 PIS.pdf |
| Scientific title | A parallel-design randomized controlled trial investigating the treatment of metabolic acidosis in patients with chronic kidney disease with either sodium citrate versus sodium bicarbonate |
| Study acronym | SoCiB |
| Study hypothesis | Data support the hypothesis that alkali therapy preserves kidney function in patients with CKD, but there is no clinical trial comparing sodium citrate with sodium bicarbonate for metabolic acidosis in chronic kidney disease. |
| Ethics approval(s) | Approved 20/09/2021, Fundeni Clinical Institute (Fundeni Street no. 258, 022328, Bucharest, Romania; +40 (0)724545131; secretariat@icfundeni.ro), ref: 59531 |
| Condition | Alkali therapy of metabolic acidosis in patients with chronic kidney disease |
| Intervention | Based on their level of serum bicarbonate, subjects will receive either high doses or low doses of sodium bicarbonate or sodium citrate. Computer-generated randomization will be performed using online software to generate block randomization. Group 1: treatment will be started with sodium bicarbonate 600 mg/d if serum bicarbonate is 19-22 mEq/l or 600 mg twice daily if serum bicarbonate is under 18 mEq/l and if serum bicarbonate is still under the target value at next visits, increase sodium bicarbonate by one tablet to a maximum dose of 3600 mg. Group 2: treatment will be started with sodium citrate 1691 mg/306 mg/d if serum bicarbonate is 19-22 mEq/l or sodium citrate 1691 mg/306 mg twice daily if serum bicarbonate is under 18 mEq/l and if serum bicarbonate is still under the target value at next visits, increase sodium citrate taking the oral solution twice, thrice or four times per day to a maximum dose of 7988 mg. Clinical and laboratory measurements will be performed as follows: - at baseline and at the end of the study period: urinary albumin/creatinine ratio (RAC), serum soluble plasminogen activator urokinase receptor (suPAR) and arterial stiffness - at one month: 24 hour Ambulatory Blood Pressure Monitoring (ABPM) - monthy: Paraclinical parameters: eGFR ml/min/1.73 m², serum creatinine, urea, sodium, potassium, chloride, bicarbonate, albumin, urinary pH and 24-hour urinary potassium Clinical parameters: systolic and diastolic pressure, body weight, digestive symptoms |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | sodium bicarbonate, sodium citrate |
| Primary outcome measure | Decline in renal function assessed by changes in eGFR (CKD-EPI equation) and change in serum bicarbonate assessed by a venous blood sample from baseline (Bs) and monthly to the end of the study (EOS) (12 months) |
| Secondary outcome measures | 1. All-cause mortality measured using patient records at the end of the study 2. ESRD measured using a blood sample for CKD-EPI Equation for Glomerular Filtration Rate (GFR) at baseline (Bs) and monthly to the end of the study (EOS). 3. Urinary albumin/creatinine ratio (RAC) measured from a spot urine sample at baseline (Bs) and monthly to the end of the study (EOS). 4. Serum albumin measured using blood sample at baseline (Bs) and monthly to the end of the study (EOS). 5. Serum soluble plasminogen activator urokinase receptor (suPAR) measured from a venous blood sample at baseline (Bs) and monthly to the end of the study (EOS). 6. Arterial stiffness measured by sphygmoCor technology (pulse wave analysis) at baseline (Bs) and monthly to the end of the study (EOS). Safety endpoints Percentage of patients who develop during the study: 1. Blood pressure >140/90 mmHg measured using a manual sphygmomanometer 2. Hypervolemia - peripheral edema or dyspnea with crackles (appreciated clinically and on auscultation with a stethoscope) or high blood pressure needing initiation or escalation of antihypertensive medication or diuretics measured using a manual sphygmomanometer 3. Hypokalemia < 3 mEq/l measured using a blood sample 4. Serum bicarbonate >28 mEq/L measured using a blood sample 5. Calciphylaxis diagnosed by clinical presentation 6. Digestive symptoms (nausea, vomiting) by self report |
| Overall study start date | 20/09/2021 |
| Overall study end date | 01/01/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 50 |
| Participant inclusion criteria | 1. Age >18 years 2. eGFR 15-45 ml/min/1.73 m² CKD EPI 3. Serum bicarbonate 10-22 mmol/l on to two different ocassions 4. Ability to travel to study visits 5. Ability to follow the study treatment regimen 6. A wash-out period of one month if previous alkali therapy (such as sodium bicarbonate, sodium citrate, potassium citrate, baking soda, etc) |
| Participant exclusion criteria | 1. Hipokalemia <3 meq/l 2. Uncontrolled blood pressure (>150/90 mmhg under treatment with more than 3 different classes of antihypertensive drugs, including diuretics) 3. Heart failure with active class III or IV New York Heart Association, known left ventricular ejection fraction ≤30%, or hospital admission for heart failure within the past 3 months 4. Hypervolemia of any cause (nephrotic syndrome, liver, or heart failure) considered unsafe for the patient by the PI for the patient 5. Active hepatic disease 6. Chronic gastrointestinal disorder (treatment adherence unreliable) 7. Active malignancy 8. Pregnancy 9. Patients taking amilorid or sevelamer 10. Patients refusing to sign the informed consent |
| Recruitment start date | 01/01/2022 |
| Recruitment end date | 01/01/2023 |
Locations
Countries of recruitment
- Romania
Study participating centre
Fundeni Street no. 258 District no. 2
Bucharest
022328
Romania
Sponsor information
Hospital/treatment centre
Fundeni Street no. 258
Bucuresti - Sector 2
022328
Romania
| Phone | +40 (0)722792429 |
|---|---|
| gener.ismail@umfcd.ro | |
| Website | https://icfundeni.ro/ |
"ROR" |
https://ror.org/05w6fx554 |
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | 01/08/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in nephrology journals such as American Journal of Kidney Diseases, BCM Nephrology, Kidney International etc. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Gener Ismail (gener732000@yahoo.com). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | in Romanian | 22/09/2021 | No | Yes | |
| Protocol file | 22/09/2021 | No | No |
Additional files
- 40456 Protocol.pdf
- 40456 PIS.pdf
- in Romanian
Editorial Notes
05/10/2021: The study contact has been updated and the plain English summary has been updated accordingly.
22/09/2021: Trial's existence confirmed by Fundeni Clinical Institute.
