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, 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.
Tutkimuksen yleiskatsaus
Tila
Interventio / Hoito
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Vaihe
- Ei sovellettavissa
Yhteystiedot ja paikat
Opiskeluyhteys
- Nimi: Azza KHEDHIRI, MD
- Puhelinnumero: +21623146019
- Sähköposti: ik4m23@gmail.com
Tutki yhteystietojen varmuuskopiointi
- Nimi: Lobna Ben Mahmoud, MD, PhD, Professor
- Puhelinnumero: +21696365092
- Sähköposti: benmahmoud_lobna@medecinesfax.org
Opiskelupaikat
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Sfax, Tunisia, 3080
- Social security fund polyclinic
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Ottaa yhteyttä:
- Lobna Ben Mahmoud, MD, PhD, Professor
- Puhelinnumero: +21696365092
- Sähköposti: benmahmoud_lobna@medecinesfax.org
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Ottaa yhteyttä:
- Azza KHEDHIRI, MD
- Puhelinnumero: +216 23146019
- Sähköposti: ik4m23@gmail.com
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Päätutkija:
- Azza KHEDHIRI, MD
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
- Aikuinen
- Vanhempi Aikuinen
Hyväksyy terveitä vapaaehtoisia
Kuvaus
Inclusion Criteria:
- 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.
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.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Kokeellinen: 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").
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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.
Muut nimet:
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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).
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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). |
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Ei väliintuloa: 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
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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Change in Predialysis Serum Bicarbonate ("Reserves Alcalines") Between Day 0 and Day 42
Aikaikkuna: From baseline (Day 0) to Day 42
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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.
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From baseline (Day 0) to Day 42
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Proportion of Patients Achieving Target Serum Bicarbonate at Day 42
Aikaikkuna: Day 42
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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 (%).
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Day 42
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Weekly Kinetics of Predialysis Serum Bicarbonate
Aikaikkuna: Day 0, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42.
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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.
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Day 0, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42.
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Intradialytic hypotension episodes
Aikaikkuna: From baseline (Day 0) to Day 42
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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). |
From baseline (Day 0) to Day 42
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Dialysis Adequacy
Aikaikkuna: From baseline (Day 0) to Day 42
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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.
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From baseline (Day 0) to Day 42
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Predialysis Serum Sodium
Aikaikkuna: From baseline (Day 0) to Day 42
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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.
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From baseline (Day 0) to Day 42
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Dialysis symptom burden
Aikaikkuna: Baseline (day 0), day 21, and day 42 (end of treatment).
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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. |
Baseline (day 0), day 21, and day 42 (end of treatment).
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Change in serum Calcium
Aikaikkuna: From baseline (Day 0) and Day 42
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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.
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From baseline (Day 0) and Day 42
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Change in serum Phosphorus
Aikaikkuna: From baseline (Day 0) and Day 42
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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.
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From baseline (Day 0) and Day 42
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Change in Serum Parathormone (PTH)
Aikaikkuna: From baseline (Day 0) and Day 42
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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.
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From baseline (Day 0) and Day 42
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Change in serum albumin
Aikaikkuna: Baseline and week 6 (end of intervention)
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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.
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Baseline and week 6 (end of intervention)
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Change in interdialytic weight gain
Aikaikkuna: Baseline (week 1) and the end of the intervention (week 6)
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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.
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Baseline (week 1) and the end of the intervention (week 6)
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Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Feasibility of the Pilot Trial
Aikaikkuna: From study start (screening and inclusion) to Day 42
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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.
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From study start (screening and inclusion) to Day 42
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Yhteistyökumppanit ja tutkijat
Sponsori
Tutkijat
- Opintojohtaja: Lobna Ben Mahmoud, MD, PhD, Professor, University of Sfax, Faculty of medecine of Sfax
- Opintojen puheenjohtaja: Ahmed Hakim, MD, Professor, University of Sfax, Faculty of medecine of Sfax
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Arvioitu)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Urogenitaaliset sairaudet
- Patologiset prosessit
- Miesten urogenitaaliset sairaudet
- Munuaissairaudet
- Urologiset sairaudet
- Naisten virtsa- ja sukupuolielinten sairaudet
- Naisten virtsa- ja sukupuolielinten sairaudet ja raskauden komplikaatiot
- Krooninen sairaus
- Sairauden ominaisuudet
- Metaboliset sairaudet
- Munuaisten vajaatoiminta
- Munuaisten vajaatoiminta, krooninen
- Happo-emäs-epätasapaino
- Patologiset tilat, merkit ja oireet
- Ravitsemukselliset ja aineenvaihduntataudit
- Munuaisten vajaatoiminta, krooninen
- Asidoosi
- Epäorgaaniset kemikaalit
- Natriumyhdisteet
- Hiiliyhdisteet, epäorgaaniset
- Karbonaatti
- Hiilihappo
- Bikarbonaatit
- Natriumbikarbonaatti
Muut tutkimustunnusnumerot
- BICARDIS-2026-01
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
IPD-suunnitelman kuvaus
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.
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