Chronic Hemodialysis, End-stage Renal Disease (ESRD), Metabolic Acidosis
Conditions
Keywords
Hemodialysis, End-Stage Renal Disease, Metabolic Acidosis, Oral sodium Bicarbonate, Dialysate Bicarbonate, Pilot Trial, Bicarbonate Supplementation
Brief summary
Metabolic acidosis is frequent in chronic hemodialysis patients and is associated with adverse clinical outcomes. Two commonly used strategies to correct acidosis are oral sodium bicarbonate supplementation and increasing the bicarbonate concentration of the dialysate, but their comparative effectiveness and tolerance in routine care remain uncertain. This pilot, prospective, randomized, open-label, two-center trial will compare oral sodium bicarbonate versus higher dialysate bicarbonate in chronic hemodialysis patients with metabolic acidosis, using predialysis plasma bicarbonate concentrations, so-called "reserves alcalines" or "alkaline reserves" in local laboratory reports, as a pragmatic marker of acid-base status. Approximately 30 acidotic patients (serum bicarbonate \< 22 mmol/L) will be randomized 1:1 to receive either oral sodium bicarbonate or an increase in dialysate bicarbonate for 6 weeks. An additional non-acidotic observational group will provide descriptive reference data. The primary outcome is the change in predialysis serum bicarbonate from baseline (Day 0) to Day 42 between the two randomized arms. Secondary outcomes include the proportion of patients reaching target serum bicarbonate levels, the weekly kinetics of correction, dialysis adequacy (Kt/V and online clearance monitoring), intradialytic tolerance (blood pressure, cramps, hypotension, symptoms), and sodium-related safety (natremia, interdialytic weight gain). Feasibility indicators such as recruitment, retention, adherence to treatment and dialysate adjustment, and data completeness will also be described to inform the design of a larger definitive trial.
Detailed description
Metabolic acidosis is a common complication in chronic hemodialysis patients and is associated with adverse nutritional, cardiovascular, and bone outcomes. In clinical practice, two main strategies are used to correct acidosis: oral sodium bicarbonate supplementation and increasing the bicarbonate concentration of the dialysate. Both approaches are recommended in guidelines, but their comparative effectiveness and tolerance in routine hemodialysis care, particularly in resource-limited settings, remain uncertain. This pilot, prospective, randomized, open-label, multicenter study will compare these two strategies in adult chronic hemodialysis patients with metabolic acidosis, defined by low predialysis serum (or plasma) bicarbonate concentrations, so-called "reserves alcalines" or "alkaline reserves" in local laboratory reports. Approximately 30 acidotic patients (serum bicarbonate \< 22 mmol/L) will be enrolled and randomized in a 1:1 ratio to either oral sodium bicarbonate supplementation (Arm A) or an increase in dialysate bicarbonate concentration (Arm B) for 6 weeks. In addition, a non-acidotic observational control group of hemodialysis patients with stable, adequate serum bicarbonate levels will be followed descriptively to provide reference data on acid-base status, dialysis adequacy, and tolerance. Randomization among acidotic patients will be performed after matching them in pairs according to the severity of metabolic acidosis (baseline predialysis serum bicarbonate / "reserves alcalines") and age. Patients will be ordered from the lowest to the highest serum bicarbonate value, then matched two-by-two on similar bicarbonate level and age. Within each pair, allocation to oral sodium bicarbonate (Arm A) or increased dialysate bicarbonate (Arm B) will be determined by a computer-generated random number in a spreadsheet, corresponding to a block randomization with block size 2 after matching on acidosis severity. The non-acidotic control group will not be randomized and will receive usual care. The primary outcome is the change in predialysis serum bicarbonate from baseline (Day 0) to Day 42, comparing the two randomized arms. Secondary outcomes include the proportion of patients achieving target serum bicarbonate at Day 42, the weekly kinetics of bicarbonate correction over 6 weeks, changes in serum potassium, and dialysis adequacy assessed by Kt/V and online clearance monitoring. Intradialytic and interdialytic tolerance will be evaluated through blood pressure, interdialytic weight gain, cramps, hypotension, thirst, digestive symptoms, and any treatment discontinuation or dose reduction related to intolerance. Sodium-related safety will be assessed by predialysis natremia and interdialytic weight gain, given the potential impact of both oral sodium bicarbonate and higher dialysate bicarbonate on sodium load. As a pilot trial, this study also includes predefined feasibility objectives. Feasibility outcomes will describe recruitment and retention rates, adherence to oral treatment and to the dialysate bicarbonate adjustment algorithm, and data completeness for key clinical and laboratory variables. These feasibility indicators will be used to judge the practicality of the protocol and to inform the design and assumptions of a larger, definitive randomized controlled trial.
Interventions
DIETARY_SUPPLEMENTOral sodium bicarbonate
Oral sodium bicarbonate given as Bicardis 500 mg capsules, used as a dietary supplement in Tunisia, administered according to a standardized algorithm based on predialysis serum bicarbonate concentrations, so-called "reserves alcalines" in local laboratory reports. At baseline, an initial dose is prescribed according to the severity of metabolic acidosis: 1 capsule/day if 20-21.9, 2 capsules/day if 18-19.9, 3 capsules/day if 16-17.9, 4 capsules/day if \<16 mmol/L. At each weekly visit, the same dose is maintained if reserves alcalines remain below the target range and the weekly increase is ≤ 3 mmol/L; the dose is reduced to the previous lower level if the weekly increase is \> 3 mmol/L or if predialysis bicarbonate enters the predefined target range (22-24 mmol/L); oral bicarbonate is reduced or stopped if predialysis bicarbonate exceeds the upper limit of the target range (\> 24 mmol/L) to avoid alkalosis, and the dose is increased if reserves alcalines do not improve or decrease.
OTHERIncreased Dialysate Bicarbonate
Adjustment of the dialysate bicarbonate concentration will be performed according to a standardized titration strategy based on predialysis serum bicarbonate concentrations ("reserves alcalines" in local laboratory reports). At baseline, an initial increase in dialysate bicarbonate is prescribed according to the severity of metabolic acidosis: +1 mmol/L if serum bicarbonate is 20-21.9 mmol/L, +2 mmol/L if 18-19.9 mmol/L, +3 mmol/L if 16-17.9 mmol/L, and a larger or individualized increase if \< 16 mmol/L. At each weekly visit, dialysate bicarbonate is then adjusted as follows: it is maintained if reserves alcalines remain below the target range and the weekly increase is ≤ 3 mmol/L; it is reduced to the previous lower level if the weekly increase is \> 3 mmol/L or if predialysis bicarbonate enters the predefined target range (22-24 mmol/L); and it is reduced or returned to the standard level if predialysis bicarbonate exceeds the upper limit of the target range (\> 24 mmol/L).
Sponsors
University of Sfax
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a pilot, prospective, randomized, open-label, multicenter trial with three parallel groups. Two active arms include chronic hemodialysis patients with metabolic acidosis (serum/plasma bicarbonate \< 22 mmol/L) randomized 1:1 to oral sodium bicarbonate supplementation or increased dialysate bicarbonate concentration. Randomization among acidotic patients is performed in matched pairs according to baseline serum bicarbonate (so-called "reserves alcalines" in local laboratory reports) and age, using a computer-generated random number within each pair (block size 2) to ensure balanced acidosis severity between arms. A third non-acidotic group with stable serum bicarbonate levels is followed as an observational control and does not undergo randomization.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years. * Chronic hemodialysis for at least 3 months. * Stable hemodialysis prescription (no major change in dialysis prescription in the previous weeks, as per local practice). * Predialysis low "alkaline reserves" (serum bicarbonate concentration) according to the operational threshold used in the unit (e.g., "alkaline reserves" \< 22 mmol/L), consistent with KDIGO 2017 definition of metabolic acidosis. * Ability to give written informed consent. For the observational group: * Age ≥ 18 years. * Chronic hemodialysis for at least 3 months. * Predialysis "alkaline reserves" considered stable and within the locally defined normal range (≥ 22mmol/L). * Ability to give written informed consent.
Exclusion criteria
* Recent hemodynamic instability (e.g., repeated intradialytic hypotension or unstable blood pressure in the previous weeks). * Recent hospitalization for an acute condition. * Acute infection or major intercurrent acute event at the time of screening. * Major change in dialysis prescription in the 2 weeks prior to inclusion (e.g., change in dialysis schedule, duration, or dialysate composition outside the study protocol). * Severe digestive disorders limiting oral intake (e.g., persistent vomiting, severe malabsorption, or any condition preventing safe oral Bicardis administration). * Known hypernatremia or high risk of uncontrolled sodium and fluid overload (as judged by the investigator). * Severe uncontrolled hypercalcemia or hypocalcemia. * Any condition that, in the investigator's judgment, would preclude safe participation or interfere with study procedures (e.g., very limited life expectancy, inability to attend scheduled visits). * Refusal to participate or inability to provide written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Predialysis Serum Bicarbonate ("Reserves Alcalines") Between Day 0 and Day 42 | From baseline (Day 0) to Day 42 | Predialysis serum (or plasma) bicarbonate concentrations, so-called "reserves alcalines" or "alkaline reserves" in local laboratory reports, will be measured at baseline (Day 0) and after 6 weeks (Day 42) in chronic hemodialysis patients with metabolic acidosis. The primary outcome is the change in predialysis serum bicarbonate between Day 0 and Day 42 (Δ serum bicarbonate), comparing the oral sodium bicarbonate arm and the higher dialysate bicarbonate arm. Serum bicarbonate will be expressed in mmol/L, and metabolic acidosis at inclusion is defined as predialysis serum bicarbonate \< 22 mmol/L. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Achieving Target Serum Bicarbonate at Day 42 | Day 42 | Proportion of randomized acidotic hemodialysis patients in each active arm (oral sodium bicarbonate vs higher dialysate bicarbonate) who achieve a predialysis serum (or plasma) bicarbonate level within the predefined target range at Day 42. Serum bicarbonate corresponds to "reserves alcalines" or "alkaline reserves" in local laboratory reports and will be expressed in mmol/L. Proportion will be expressed as a percentage of each active arm (%). |
| Weekly Kinetics of Predialysis Serum Bicarbonate | Day 0, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42. | Trajectory of predialysis serum (or plasma) bicarbonate ("reserves alcalines" / "alkaline reserves") over the 6-week study period, measured at baseline (Day 0) and weekly at Days 7, 14, 21, 28, 35 and 42, comparing the oral sodium bicarbonate and higher dialysate bicarbonate arms. Results will be expressed as absolute values (mmol/L) and changes from baseline at each time point. |
| Intradialytic hypotension episodes | From baseline (Day 0) to Day 42 | Number of intradialytic hypotension episodes per patient over 6 weeks in each treatment arm. Intradialytic hypotension is defined as: Systolic blood pressure (SBP) \< 90 mmHg or a decrease in SBP ≥ 20 mmHg compared with the pre-dialysis value, accompanied by at least one intolerance symptom (such as cramps, nausea, dizziness, or other intradialytic complaints). |
| Dialysis Adequacy | From baseline (Day 0) to Day 42 | Dialysis adequacy assessed by single-pool Kt/V and online clearance monitoring (OCM), measured weekly or according to local routine, in the oral sodium bicarbonate and higher dialysate bicarbonate arms. The outcome will describe the stability of Kt/V and OCM over the 6-week period and compare any changes between arms. |
| Predialysis Serum Sodium | From baseline (Day 0) to Day 42 | Predialysis serum sodium concentration (natremia), expressed in mmol/L, measured at baseline and weekly up to Day 42, to evaluate sodium-related safety in each arm. The outcome will compare changes in natremia over time between oral sodium bicarbonate and higher dialysate bicarbonate. |
| Dialysis symptom burden | Baseline (day 0), day 21, and day 42 (end of treatment). | Dialysis symptom burden will be assessed using the Dialysis Symptom Index (DSI), which records the presence and severity of common symptoms in hemodialysis patients (e.g., cramps, headaches, thirst, nausea, and fatigue). The DSI will be administered at baseline (day 0), day 21, and day 42 in each treatment arm. The reported outcome will be the change in total DSI score over time (baseline to day 21 and baseline to day 42), with higher scores indicating greater symptom burden. |
| Change in serum Calcium | From baseline (Day 0) and Day 42 | Serum total calcium concentration will be measured at baseline (Day 0) and at Day 42 in each treatment arm and in the non-acidotic control group. The outcome will describe the change in serum calcium between Day 0 and Day 42 in chronic hemodialysis patients with metabolic acidosis treated with oral sodium bicarbonate or higher dialysate bicarbonate, and in non-acidotic hemodialysis patients, in order to explore the effect of metabolic acidosis correction on calcium homeostasis and phosphocalcic balance. Serum calcium will be expressed in mmol/L. |
| Change in serum Phosphorus | From baseline (Day 0) and Day 42 | Serum phosphorus concentration will be measured at baseline (Day 0) and at Day 42 in each treatment arm and in the non-acidotic control group. The outcome will describe the change in serum phosphorus between Day 0 and Day 42 in chronic hemodialysis patients with metabolic acidosis treated with oral sodium bicarbonate or higher dialysate bicarbonate, and in non-acidotic hemodialysis patients, in order to evaluate the impact of metabolic acidosis correction on serum phosphate levels and phosphocalcic balance. Serum phosphorus will be expressed in mmol/L. |
| Change in Serum Parathormone (PTH) | From baseline (Day 0) and Day 42 | Parathormone (PTH) will be measured at baseline (Day 0) and at Day 42 in each treatment arm and in the non-acidotic control group, using an immuno-enzymatic assay according to local laboratory methods. The outcome will describe the change in PTH between Day 0 and Day 42 in chronic hemodialysis patients with metabolic acidosis treated with oral sodium bicarbonate or higher dialysate bicarbonate, and in non-acidotic hemodialysis patients, in order to explore the effect of metabolic acidosis correction on parathyroid function and renal osteodystrophy risk. Serum PTH will be expressed in pg/mL. |
Countries
Tunisia
Contacts
CONTACTAzza KHEDHIRI, MD
CONTACTLobna Ben Mahmoud, MD, PhD, Professor
STUDY_DIRECTORLobna Ben Mahmoud, MD, PhD, Professor
University of Sfax, Faculty of medecine of Sfax
STUDY_CHAIRAhmed Hakim, MD, Professor
University of Sfax, Faculty of medecine of Sfax
Outcome results
None listed