Pilot Trial of Oral Sodium Bicarbonate Versus Higher Dialysate Bicarbonate in Hemodialysis Patients With Metabolic Acidosis

Browse trials for

• Kidney Failure, Chronic 2,108
• Acidosis 111

Keywords

• Hemodialysis
• End-Stage Renal Disease
• Metabolic Acidosis
• Oral sodium Bicarbonate
• Dialysate Bicarbonate
• Pilot Trial
• Bicarbonate Supplementation

Kidney Failure, Chronic

2,108 studies on the registry are indexed under Kidney Failure, Chronic; 273 are open to participants now.

This study's planned enrollment of 37 is below the median of 57 across 1,569 interventional studies indexed under Kidney Failure, Chronic.

Lead sponsor

University of Sfax is the lead sponsor of 9 studies on the registry; 2 are open to participants now.

Study arms

• Experimental
  Oral Sodium Bicarbonate Arm

  Adult chronic hemodialysis patients with metabolic acidosis (serum/plasma bicarbonate \< 22 mmol/L) randomized to receive oral sodium bicarbonate supplementation according to a stepwise dosing algorithm based on weekly predialysis serum bicarbonate ("reserves alcalines").

  Dietary Supplement: Oral sodium bicarbonate

• Active comparator
  Increased Dialysate Bicarbonate Arm

  Adult chronic hemodialysis patients with metabolic acidosis (serum/plasma bicarbonate \< 22 mmol/L) randomized to receive an increased dialysate bicarbonate concentration according to a predefined stepwise algorithm based on weekly predialysis serum bicarbonate ("reserves alcalines" or "alkaline reserves" in local laboratory reports).

  Other: Increased Dialysate Bicarbonate

• No intervention
  Non-Acidotic Hemodialysis Control Group

  Adult chronic hemodialysis patients with stable, adequate predialysis serum (or plasma) bicarbonate concentrations (so-called "reserves alcalines" or "alkaline reserves" in local laboratory reports), who are not acidotic according to the study definition, will be included as a non-randomized observational control group. These patients will continue their usual dialysis prescription and routine care without any specific study-mandated change in oral bicarbonate or dialysate bicarbonate. They will be followed over the same 6-week period with collection of serum bicarbonate, sodium, potassium, dialysis adequacy (Kt/V and online clearance monitoring), blood pressure, interdialytic weight gain, and intradialytic symptoms, to provide descriptive reference data on acid-base status, dialysis adequacy, and tolerance in non-acidotic hemodialysis patients

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.

  Also known as: Bicardis

• 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).

Primary outcomes

1. Change in Predialysis Serum Bicarbonate ("Reserves Alcalines") Between Day 0 and 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.

   Time frame: From baseline (Day 0) to Day 42

Secondary outcomes

1. Proportion of Patients Achieving Target Serum Bicarbonate at 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 (%).

   Time frame: Day 42

2. Weekly Kinetics of Predialysis Serum Bicarbonate

   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.

   Time frame: Day 0, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42.

3. Intradialytic hypotension episodes

   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).

   Time frame: From baseline (Day 0) to Day 42

4. Dialysis Adequacy

   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.

   Time frame: From baseline (Day 0) to Day 42

5. Predialysis Serum Sodium

   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.

   Time frame: From baseline (Day 0) to Day 42

6. Dialysis symptom burden

   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.

   Time frame: Baseline (day 0), day 21, and day 42 (end of treatment).

7. Change in serum Calcium

   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.

   Time frame: From baseline (Day 0) and Day 42

8. Change in serum Phosphorus

   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.

   Time frame: From baseline (Day 0) and Day 42

9. Change in Serum Parathormone (PTH)

   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.

   Time frame: From baseline (Day 0) and Day 42

10. Change in serum albumin

    Change in serum albumin concentration (g/L) from baseline to the end of the 4-week intervention, comparing the oral Bicardis group, the increased dialysate bicarbonate group, and the control group. This outcome is used as a surrogate marker of global protein-nutritional status potentially influenced by correction of metabolic acidosis.

    Time frame: Baseline and week 6 (end of intervention)

11. Change in interdialytic weight gain

    Change in mean weekly interdialytic weight gain (kg and % of dry weight) between baseline (week 1) and the end of the intervention (week 6) in each randomized arm, to assess the impact of oral sodium bicarbonate versus higher dialysate bicarbonate on sodium and fluid balance.

    Time frame: Baseline (week 1) and the end of the intervention (week 6)

Other outcomes

1. Feasibility of the Pilot Trial

   Feasibility of the study procedures will be assessed descriptively to inform the design of a future definitive randomized trial. Feasibility outcomes include: (1) recruitment rate, defined as the proportion of eligible chronic hemodialysis patients with metabolic acidosis who consent and are enrolled; (2) retention rate, defined as the proportion of randomized participants who complete the Day 42 visit with primary outcome assessment; (3) adherence to oral sodium bicarbonate in the experimental arm, defined as the proportion of prescribed doses actually taken over 6 weeks; (4) adherence to the dialysate bicarbonate adjustment algorithm in the active comparator arm, defined as the proportion of dialysis sessions performed with a dialysate bicarbonate level consistent with the predefined weekly serum bicarbonate ("reserves alcalines"); and (5) data completeness, defined as the proportion of expected measurements available for key variables.

   Time frame: From study start (screening and inclusion) to Day 42

Individual participant data

Plan to share: Undecided — Individual participant data (IPD) from this pilot trial will not be shared publicly. The study has a small sample size in a limited number of centers, which increases the risk of re-identification of participants despite de-identification procedures. In addition, data were collected in a specific local context without prior consent for open data sharing, and current ethical approvals and institutional policies do not cover broad external data sharing. Aggregated results and methodological details will be disseminated through scientific presentations and publications, but raw IPD will remain confidential and accessible only to the investigative team and relevant oversight bodies, in accordance with applicable regulations and ethics committee requirements.