Pilot Trial of Oral Sodium Bicarbonate Versus Higher Dialysate Bicarbonate in Hemodialysis Patients With Metabolic Acidosis (Bicarbonate-HD)

Comparative Pilot Trial of Oral Sodium Bicarbonate Versus Increased Dialysate Bicarbonate in Chronic Hemodialysis Patients With Metabolic Acidosis

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 4 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 28 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.

Study Overview

• Status: Not yet recruiting
• Conditions: End-stage Renal Disease (ESRD); Metabolic Acidosis; Chronic Hemodialysis
• Intervention / Treatment: Dietary supplement: Oral sodium bicarbonate; Other: Increased Dialysate Bicarbonate

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 4 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 28, comparing the two randomized arms. Secondary outcomes include the proportion of patients achieving target serum bicarbonate at Day 28, the weekly kinetics of bicarbonate correction, 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.

• Study Type: Interventional
• Enrollment (Estimated): 37
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Azza KHEDHIRI, MD; Phone Number: +21623146019; Email: ik4m23@gmail.com
• Study Contact Backup: Name: Lobna Ben Mahmoud, MD, PhD, Professor; Phone Number: +21696365092; Email: benmahmoud_lobna@medecinesfax.org

Study Locations

• Tunisia
  • Sfax, Tunisia, 3080
    • Social security fund polyclinic
    • Contact: Lobna Ben Mahmoud, MD, PhD, Professor; Phone Number: +21696365092; Email: benmahmoud_lobna@medecinesfax.org
    • Contact: Azza KHEDHIRI, MD; Phone Number: +216 23146019; Email: ik4m23@gmail.com
    • Principal Investigator: Azza KHEDHIRI, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; Oral sodium bicarbonate given as Bicardis 500 mg capsules, used as a dietary supplement in Tunisia, administered according to a predefined stepwise dosing algorithm based on weekly predialysis serum (or plasma) bicarbonate concentrations, so-called "reserves alcalines" or "alkaline reserves" in local laboratory reports. At baseline and at each weekly visit, the dose is adapted as follows: 1 capsule/day if serum bicarbonate is 20-21.9 mmol/L, 2 capsules/day if 18-19.9 mmol/L, 3 capsules/day if 16-17.9 mmol/L, and 4 capsules/day if < 16 mmol/L, with verification of adherence and investigation of intercurrent causes in case of very low values. The daily dose may be divided into 2-3 intakes according to digestive tolerance and the patient's routine. The goal is a progressive correction of metabolic acidosis over 4 weeks without excessive sodium load or intolerance.; Other Names: Bicardis
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). At baseline, the dialysate bicarbonate prescription is adjusted as follows: +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 is considered if < 16 mmol/L, with the possibility to return to the previous level in case of post-dialysis alkalosis or intolerance. Dialysate sodium concentration is kept constant according to the unit's standard to avoid confounding between bicarbonate and sodium effects.	Other: Increased Dialysate Bicarbonate; Adjustment of the dialysate bicarbonate concentration according to a predefined stepwise algorithm based on weekly predialysis serum (or plasma) bicarbonate concentrations ("reserves alcalines" / "alkaline reserves" in local laboratory reports): +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 considered if < 16 mmol/L, with return to the previous level in case of post-dialysis alkalosis or intolerance. Dialysate sodium concentration is kept constant according to the unit's standard.
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 4-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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Predialysis Serum Bicarbonate ("Reserves Alcalines") Between Day 0 and Day 28	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 4 weeks (Day 28) in chronic hemodialysis patients with metabolic acidosis. The primary outcome is the change in predialysis serum bicarbonate between Day 0 and Day 28 (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.	From baseline (Day 0) to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Achieving Target Serum Bicarbonate at Day 28	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 28. 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 (%).	Day 28
Weekly Kinetics of Predialysis Serum Bicarbonate	Trajectory of predialysis serum (or plasma) bicarbonate ("reserves alcalines" / "alkaline reserves") over the 4-week study period, measured at baseline (Day 0) and weekly at Days 7, 14, 21, and 28, 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.	Day 0, Day 7, Day 14, Day 21, Day 28
Intradialytic hypotension episodes	Number of intradialytic hypotension episodes per patient over 4 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).	From baseline (Day 0) to Day 28
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 4-week period and compare any changes between arms.	From baseline (Week 0) to Week 4
Predialysis Serum Sodium	Predialysis serum sodium concentration (natremia), expressed in mmol/L, measured at baseline and weekly up to Day 28, 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.	From baseline (Day 0) to Day 28
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 14, and day 28 in each treatment arm. The reported outcome will be the change in total DSI score over time (baseline to day 14 and baseline to day 28), with higher scores indicating greater symptom burden.	Baseline (day 0), day 14, and day 28 (end of treatment).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 28 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 4 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.	From study start (screening and inclusion) to Day 28

Collaborators and Investigators

• Sponsor: University of Sfax
• Investigators: Study Director: Lobna Ben Mahmoud, MD, PhD, Professor, University of Sfax, Faculty of medecine of Sfax; Study Chair: Ahmed Hakim, MD, Professor, University of Sfax, Faculty of medecine of Sfax

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: June 21, 2026
• First Submitted That Met QC Criteria: July 2, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Hemodialysis; Metabolic Acidosis; End-Stage Renal Disease; Pilot Trial; Oral sodium Bicarbonate; Dialysate Bicarbonate; Bicarbonate Supplementation
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Acid-Base Imbalance; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Kidney Failure, Chronic; Acidosis; Inorganic Chemicals; Sodium Compounds; Carbon Compounds, Inorganic; Carbonates; Carbonic Acid; Bicarbonates; Sodium Bicarbonate
• Other Study ID Numbers: BICARDIS-2026-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No