Comparative Pilot Trial of Oral Sodium Bicarbonate Versus Increased Dialysate Bicarbonate in Chronic Hemodialysis Patients With Metabolic Acidosis
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Change in Predialysis Serum Bicarbonate ("Reserves Alcalines") Between Day 0 and Day 28
研究概览
简要总结
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, single-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), sodium-related safety (natremia, interdialytic weight gain), and the effects of acidosis correction on nutritional and bone-mineral metabolism, including changes in serum albumin, calcium, phosphorus, and parathyroid hormone (PTH). 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.
详细描述
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, single-center 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •Chronic hemodialysis for at least 3 months.
- •Stable hemodialysis prescription: 3 times a week, high-flux dialyzers, no major change in dialysis prescription in the previous weeks.
- •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.
- •Hemodialysis 3 times a week, high-flux dialyzers.
- •Predialysis "alkaline reserves" considered stable and within the locally defined normal range (≥ 22mmol/L).
- •Ability to give written informed consent.
排除标准
- •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.
研究组 & 干预措施
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
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).
干预措施: Increased Dialysate Bicarbonate (Other)
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").
干预措施: Oral sodium bicarbonate (Dietary Supplement)
结局指标
主要结局
Change in Predialysis Serum Bicarbonate ("Reserves Alcalines") Between Day 0 and Day 28
时间窗: From baseline (Day 0) to 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.
Change in Predialysis Serum Bicarbonate ("Reserves Alcalines") Between Day 0 and Day 42
时间窗: 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.
次要结局
- Proportion of Patients Achieving Target Serum Bicarbonate at Day 28(Day 28)
- Weekly Kinetics of Predialysis Serum Bicarbonate(Day 0, Day 7, Day 14, Day 21, Day 28)
- Intradialytic hypotension episodes(From baseline (Day 0) to Day 28)
- Dialysis Adequacy(From baseline (Week 0) to Week 4)
- Predialysis Serum Sodium(From baseline (Day 0) to Day 28)
- Dialysis symptom burden(Baseline (day 0), day 14, and day 28 (end of treatment).)
- Change in serum Calcium(Day 0 and Day 28)
- Change in serum Phosphorus(Day 0 and Day 28)
- Change in Serum Parathormone (PTH)(Day 0 and Day 28)
- Proportion of Patients Achieving Target Serum Bicarbonate at Day 42(Day 42)
- Weekly Kinetics of Predialysis Serum Bicarbonate(Day 0, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42.)
- Intradialytic hypotension episodes(From baseline (Day 0) to Day 42)
- Dialysis Adequacy(From baseline (Day 0) to Day 42)
- Predialysis Serum Sodium(From baseline (Day 0) to Day 42)
- Dialysis symptom burden(Baseline (day 0), day 21, and day 42 (end of treatment).)
- Change in serum Calcium(From baseline (Day 0) and Day 42)
- Change in serum Phosphorus(From baseline (Day 0) and Day 42)
- Change in Serum Parathormone (PTH)(From baseline (Day 0) and Day 42)
- Change in serum albumin(Baseline and week 6 (end of intervention))
- Change in interdialytic weight gain(Baseline (week 1) and the end of the intervention (week 6))
研究者
Azza KHEDHIRI
Principal investigator, Head of the Hemodialysis Department of the Sfax Social Security fund polyclinic
University of Sfax