Acute Kidney InjuryPhase 4ESCALATENCT07464431
Sodium Bicarbonate for Critically Ill Patients With Metabolic Acidosis and Acute Kidney Injury
A Phase 4 study testing Sodium Bicarbonate 8.4% Solution for Injection and Balanced crystalloid solution in people with Acute Kidney Injury and Metabolic Acidosis, run by Universität Münster at 1 site in Germany.
Trial summary
The study investigates whether sodium bicarbonate is able to reduce the occurrence of major adverse kidney events on day 90 (MAKE90) in critically ill patients with metabolic acidosis and acute kidney injury (AKI). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Kidney Injury, Metabolic Acidosis, Critical Illness
- What is being tested?
- Sodium Bicarbonate 8.4% Solution for Injection and Balanced crystalloid solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 660 participants
- Where
- 1 siteGermany
- Study dates
- 7 May 2026to Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult ≥ 18 years
- Critically ill patients (requiring treatment on an ICU or IMC)
- Metabolic acidosis, defined as all of the following:
- Arterial pH ≤7.25
- PaCO2 < 6.5kPa (<49 mmHg)
- Standard bicarbonate ≤20 mmol/L
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- Standard Base Excess <-2
- AKI stage 2 or 3 of the KDIGO classification
- Written informed consent of the patient or legal representative or authorized representative or emergency inclusion (according to Article 35 EU-Regulation 536/2014)
Who cannot join
- Pregnant or breastfeeding patients
- Respiratory acidosis (acute or chronic) [dynamic, and if corrected, patient may be reconsidered for the trial]
- Patients on KRT, or KRT immediately indicated and treating clinician(s) unwilling to defer
- Deemed unsuitable for KRT
- High output stoma/ileostomy
- Percutaneous biliary drainage
Show all 16Show fewer
- End stage kidney failure defined as documented eGFR <15ml/min/1.73m 2 prior to onset of this acute illness or end stage kidney disease (ESKD) on dialysis
- Known renal tubular acidosis
- Diabetic ketoacidosis
- High anion gap acid poisoning (e.g. polyethylene glycol (PEG), aspirin, methanol)
- Symptomatic hypocalcaemia (Ionized calcium <1.05 mmol/L)[dynamic, and if corrected, patient may be reconsidered for the trial]
- Hypernatremia (plasma sodium >150 mmol/L)[dynamic, and if corrected, patient may be reconsidered for the trial]
- Severe hypokalemia (potassium <3.0 mmol/L)[dynamic, and if corrected, patient may be reconsidered for the trial]
- Death perceived as imminent
- Known hypersensitivity to sodium bicarbonate or EDTA (Disodiumedetate)
- Previously randomized into ESCALATE
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
University Münster, University Hospital Münster
Münster, 48149
About this study
Official title: Evaluating the Clinical Effectiveness of Sodium Bicarbonate for Critically Ill Patients With Metabolic Acidosis and Acute Kidney Injury (ESCALATE)
The study investigates whether sodium bicarbonate is able to reduce the occurrence of major adverse kidney events on day 90 (MAKE90) in critically ill patients with metabolic acidosis and acute kidney injury (AKI). While its efficacy in this context has been suggested in a subgroup analysis of the BICAR-ICU trial it has not been confirmed in a double-blinded randomized controlled trial to date.
Read the detailed description
Each year > 200 000 adult patients are admitted to intensive-care units (ICUs) in Germany of which around half develop acute kidney injury (AKI). AKI markedly increases morbidity, mortality, ICU/hospital length of stay, and the risk of progression to chronic kidney disease.2-4 Metabolic acidosis significantly raises hospital mortality, the need for kidney-replacement therapy (KRT), and the incidence of major adverse kidney events within 30 days (MAKE30).5,6 When AKI and metabolic acidosis coexist, 90-day mortality ranges from 53 % to 59 % (vs 26 % for AKI alone).
Acidaemia depresses cardiovascular function through reduced myocardial contractility, impaired catecholamine responsiveness, hyperkalaemia, pulmonary vasoconstriction and arrhythmogenesis.7,8 Restoring extracellular pH is therefore biologically plausible as a strategy to improve organ perfusion and outcomes.
Sodium bicarbonate is the most widely used buffer in clinical practice, yet high-quality evidence for its benefit in AKI with metabolic acidosis is lacking. To date, despite numerous calls for appropriately designed studies, there have only been two RCTs primarily addressing the effects of sodium bicarbonate in critically ill patients with severe acidosis.1,9 Due to methodological limitations (open-label study design, selection bias, risk of confounding) and lack in generalizability, the question on using sodium bicarbonate in critically ill patients with AKI and metabolic acidosis cannot be answered with certainty.
The "Evaluating the clinical effectiveness of sodium bicarbonate for critically ill patients with metabolic acidosis and acute kidney injury" trial is a multicenter, double-blinded, randomized controlled trial. It is designed to determine whether treatment with intravenous 8.4% weight/volume (w/v) sodium bicarbonate is superior to placebo in terms of the composite endpoint major adverse kidney events (MAKE) at day 90 (composite of death from any cause, receipt of any KRT within the 90-day period, or persistent renal dysfunction (defined as a creatinine value ≥200% of the baseline value) at day 90) in critically ill patients with AKI (KDIGO stage 2 or 3) and metabolic acidosis. The findings of the ESCALATE trial are expected to have significant implications for clinical practice and patient outcomes, both in Germany and internationally, by providing high-quality evidence to guide the management of a critically ill population with high risk of mortality.
- Conditions
- Acute Kidney Injury, Metabolic Acidosis, Critical Illness
- Being tested
- Sodium Bicarbonate 8.4% Solution for Injection, Balanced crystalloid solution
- Keywords
- Acute kidney injury, Metabolic acidosis, Critical illness, Sodium bicarbonate
- Medical subject headings
- Acute Kidney Injury, Acidosis, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium Bicarbonate 8.4% Solution for InjectionDrug
Intravenous infusion according to the treatment algorithm. Infusion starts with 100ml/hr until a pH of 7.30 - 7.35 and a Base Excess of ≥ 0 is reached. Then, infusion is reduced to 25ml/hr and maintained for 5 hours. After 5 hours, infusion is titrated to a pH of >7.30.
Balanced crystalloid solutionDrug
Intravenous infusion according to the treatment algorithm. Infusion starts with 100ml/hr until a pH of 7.30 - 7.35 and a Base Excess of ≥ 0 is reached. Then, infusion is reduced to 25ml/hr and maintained for 5 hours. After 5 hours, infusion is titrated to a pH of >7.30.
| Study group | Role | What they receive |
|---|---|---|
| Sodium Bicarbonate | Experimental | Experimental: Sodium Bicarbonate 8.4% w/v Intravenous infusion according to the treatment algorithm targeting a pH>7.30 Receives: Drug: Sodium Bicarbonate 8.4% Solution for Injection |
| Balanced crystalloid solution | Placebo comparator | Placebo: Balanced crystalloid solution Intravenous infusion according to the treatment algorithm targeting a pH>7.30 Receives: Drug: Balanced crystalloid solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
MAKE90 (consisting of mortality, dialysis within 90 days, persistent renal dysfunction (defined as serum creatinine ≥ 2x compared to baseline value at day 90)
Measured: 90 days after randomization
Secondary outcomes (5)
90-day all-cause mortality (%)
Measured: 90 days after randomization
Elevation of the creatinine level to ≥200% of base value at day 90 (one measurement between day 80 and 120 after randomization)
Measured: 80 - 120 days after randomization
Receipt of any form of KRT within the 90-day time period after randomization
Measured: 90 days after randomization
KRT-dependence on day 90
Measured: 90 days after randomization
KRT-free days, defined as difference between number of days receiving KRT of any form between randomization and day 90 and number of days alive
Measured: 90 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2026
- Study start7 May 2026
- Primary completionJun 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 660 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universität Münster
- Sponsor type
- University, hospital or other
- Collaborators
- German Research Foundation
- Responsible party
- Sponsor
- Investigators
- Alexander Zarbock, MD, Study chair, University Hospital Muenster, Dept. of Anesthesiology, Intensive Care Medicine and Pain Therapy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07464431
- Sponsor's protocol ID
- UniMS23_0017
- Other IDs
- 538117253, 2025-523914-10-00, 2025
- Acronym
- ESCALATE
- Status last verified
- Sep 2026
- First submitted
- 11 Feb 2026
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this study, after deidentification (text, tables, figures, and appendices)
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Clinical Effectiveness of Sodium Bicarbonate for Critically Ill Patients With Metabolic Acidosis and Acute Kidney Injury (ESCALATE)
- ClinicalTrials.gov ID
- NCT07464431
- Acronym / sponsor ID
- ESCALATE / UniMS23_0017
- Conditions
- Acute Kidney Injury, Metabolic Acidosis, Critical Illness
- Keywords
- Acute kidney injury, Metabolic acidosis, Critical illness, Sodium bicarbonate
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 660 participants (estimated)
- Lead sponsor
- Universität MünsterUniversity, hospital or other
- Collaborators
- German Research Foundation
- Study start
- 7 May 2026 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 11 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study investigates whether sodium bicarbonate is able to reduce the occurrence of major adverse kidney events on day 90 (MAKE90) in critically ill patients with metabolic acidosis and acute kidney injury (AKI). While its efficacy in this context has been suggested in a subgroup analysis of the BICAR-ICU trial it has not been confirmed in a double-blinded randomized controlled trial to date.
Detailed description
Each year > 200 000 adult patients are admitted to intensive-care units (ICUs) in Germany of which around half develop acute kidney injury (AKI). AKI markedly increases morbidity, mortality, ICU/hospital length of stay, and the risk of progression to chronic kidney disease.2-4 Metabolic acidosis significantly raises hospital mortality, the need for kidney-replacement therapy (KRT), and the incidence of major adverse kidney events within 30 days (MAKE30).5,6 When AKI and metabolic acidosis coexist, 90-day mortality ranges from 53 % to 59 % (vs 26 % for AKI alone).
Acidaemia depresses cardiovascular function through reduced myocardial contractility, impaired catecholamine responsiveness, hyperkalaemia, pulmonary vasoconstriction and arrhythmogenesis.7,8 Restoring extracellular pH is therefore biologically plausible as a strategy to improve organ perfusion and outcomes.
Sodium bicarbonate is the most widely used buffer in clinical practice, yet high-quality evidence for its benefit in AKI with metabolic acidosis is lacking. To date, despite numerous calls for appropriately designed studies, there have only been two RCTs primarily addressing the effects of sodium bicarbonate in critically ill patients with severe acidosis.1,9 Due to methodological limitations (open-label study design, selection bias, risk of confounding) and lack in generalizability, the question on using sodium bicarbonate in critically ill patients with AKI and metabolic acidosis cannot be answered with certainty.
The "Evaluating the clinical effectiveness of sodium bicarbonate for critically ill patients with metabolic acidosis and acute kidney injury" trial is a multicenter, double-blinded, randomized controlled trial. It is designed to determine whether treatment with intravenous 8.4% weight/volume (w/v) sodium bicarbonate is superior to placebo in terms of the composite endpoint major adverse kidney events (MAKE) at day 90 (composite of death from any cause, receipt of any KRT within the 90-day period, or persistent renal dysfunction (defined as a creatinine value ≥200% of the baseline value) at day 90) in critically ill patients with AKI (KDIGO stage 2 or 3) and metabolic acidosis. The findings of the ESCALATE trial are expected to have significant implications for clinical practice and patient outcomes, both in Germany and internationally, by providing high-quality evidence to guide the management of a critically ill population with high risk of mortality.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sodium Bicarbonate | Experimental | Drug: Sodium Bicarbonate 8.4% Solution for InjectionExperimental: Sodium Bicarbonate 8.4% w/v Intravenous infusion according to the treatment algorithm targeting a pH>7.30 |
| Balanced crystalloid solution | Placebo comparator | Drug: Balanced crystalloid solutionPlacebo: Balanced crystalloid solution Intravenous infusion according to the treatment algorithm targeting a pH>7.30 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Adult ≥ 18 years
- Critically ill patients (requiring treatment on an ICU or IMC)
- Metabolic acidosis, defined as all of the following:
- AKI stage 2 or 3 of the KDIGO classification
- Written informed consent of the patient or legal representative or authorized representative or emergency inclusion (according to Article 35 EU-Regulation 536/2014)
Key exclusion criteria (16 listed)
- Pregnant or breastfeeding patients
- Respiratory acidosis (acute or chronic) [dynamic, and if corrected, patient may be reconsidered for the trial]
- Patients on KRT, or KRT immediately indicated and treating clinician(s) unwilling to defer
- Deemed unsuitable for KRT
- High output stoma/ileostomy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium Bicarbonate 8.4% Solution for InjectionIntravenous infusion according to the treatment algorithm. Infusion starts with 100ml/hr until a pH of 7.30 - 7.35 and a Base Excess of ≥ 0 is reached. Then, infusion is reduced to 25ml/hr and maintained for 5 hours. After 5 hours, infusion is titrated to a pH of >7.30. | Drug | Sodium Bicarbonate |
| Balanced crystalloid solutionIntravenous infusion according to the treatment algorithm. Infusion starts with 100ml/hr until a pH of 7.30 - 7.35 and a Base Excess of ≥ 0 is reached. Then, infusion is reduced to 25ml/hr and maintained for 5 hours. After 5 hours, infusion is titrated to a pH of >7.30. | Drug | Balanced crystalloid solution |
Primary outcome
MAKE90 (consisting of mortality, dialysis within 90 days, persistent renal dysfunction (defined as serum creatinine ≥ 2x compared to baseline value at day 90)
Time frame: 90 days after randomization
5 secondary outcomes
90-day all-cause mortality (%)
Time frame: 90 days after randomization
Elevation of the creatinine level to ≥200% of base value at day 90 (one measurement between day 80 and 120 after randomization)
Time frame: 80 - 120 days after randomization
Receipt of any form of KRT within the 90-day time period after randomization
Time frame: 90 days after randomization
KRT-dependence on day 90
Time frame: 90 days after randomization
KRT-free days, defined as difference between number of days receiving KRT of any form between randomization and day 90 and number of days alive
Time frame: 90 days after randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this study, after deidentification (text, tables, figures, and appendices)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alexander Zarbock, MD study chair
University Hospital Muenster, Dept. of Anesthesiology, Intensive Care Medicine and Pain Therapy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sodium Bicarbonate 8.4% Solution for Injection and Balanced crystalloid solution in people with Acute Kidney Injury and Metabolic Acidosis, run by Universität Münster at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alexander Zarbock, MD (+49251-8347255, ESCALATE@ukmuenster.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MAKE90 (consisting of mortality, dialysis within 90 days, persistent renal dysfunction (defined as serum creatinine ≥ 2x compared to baseline value at day 90) (time frame: 90 days after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.