Metabolic AcidosisNCT05842369
ADVOS® Versus CVVHD in Metabolic or Mixed Acidosis
A study testing ADVOS and CVVHD in people with Metabolic Acidosis, run by Universitätsklinikum Hamburg-Eppendorf at 1 site in Germany.
Trial summary
The aim of the study is to investigate the effects of ADVOS® therapy in critically ill patients with acute kidney injury, necessity of renal replacement therapy and acidosis. The investigators aim at assessing superiority of ADVOS® versus CVVHD for the primary outcome hours alive with normal pH (arterial pH ≤ 7,35)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metabolic Acidosis
- What is being tested?
- ADVOS and CVVHD
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteGermany
- Study dates
- 17 Apr 2023to 1 Jul 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Metabolic or mixed acidosis with pH ≤ 7.25 and base excess ≤ -6 mmol/l
- Age ≥ 18 years
- Acute kidney injury with need for Renal Replacement Therapy (RRT)
Who cannot join
- Pregnancy
- Wards of the state/Prisoners
- Expected survival of less than 24 hours
- Contraindication for citrate anticoagulation
- Extracorporeal membrane oxygenation (ECMO)
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
University Medical Center Hamburg-Eppendorf
Hamburg, 20246
Olaf Boenisch, MD, +49 40 741035315, o.boenisch@uke.de
Dominik Jarczak, MD, +49 40 741035315, d.jarczak@uke.de
About this study
Official title: Comparison of Two Approved Dialysis Methods for Treatment of Metabolic or Mixed Acidosis in Critically Ill Patients With Acute Kidney Injury and Indication for Renal Replacement Therapy
The aim of the study is to investigate the effects of ADVOS® therapy in critically ill patients with acute kidney injury, necessity of renal replacement therapy and acidosis.
The investigators aim at assessing superiority of ADVOS® versus CVVHD for the primary outcome hours alive with normal pH (arterial pH ≤ 7,35) until 24 hours in a modified intention-to-treat analysis (mITT: replacement if dropped out before treatment start).
Read the detailed description
Acute kidney injury (AKI) is frequently seen in patients treated at intensive care unit (ICU) and is associated with high morbidity and mortality. AKI occurs in more than 30% of critically ill patients. Various definitions for AKI have been used in the last decades, as a consequence reported incidence rates vary considerably from 13 to 78% in critically ill patients. AKI reflects a broad spectrum of clinical presentations, ranging from mild to se-vere injury, which may result in permanent loss of renal function. AKI is generally detected by a decrease in urine output (oliguria, anuria) and by an increase of renal serum markers (creatinine, blood-urea-nitrogen) with subsequent disorders in electrolyte homeostasis (e.g. hyperkalemia) and acid-base-regulation by means of metabolic acidosis. The AKIN criteria are well established criteria for diagnosis of AKI.
Different factors have been associated with development of AKI in critically ill patients. Age and pre-existing comorbidities are risk factors for development of AKI. Furthermore, infection and sepsis seem to be a mayor trigger for AKI. More than 50% of patients with septic shock develop AKI. Besides this radiocontrast agents, rapid progressive glomerulonephritis, rhabdomyolysis, trauma, circulatory shock, cardiac surgery, major non-cardiac surgery, nephrotoxic drugs and other causes are capable inducing AKI.
Metabolic acidosis, a frequent finding in AKI, is diagnosed when serum pH is reduced (pH < 7,35) and serum bicarbonate levels are abnormally low. Three major mechanisms lead to metabolic acidosis: 1) increased acid generation 2) loss of bicarbonate 3) decreased renal acid excretion. In AKI reduction of urine output and dimi-nished renal acid excretion results in subsequent metabolic acidosis.
Typical indications for renal replacement therapy (RRT) are hyperkalaemia, severe metabolic acidosis, diuretic-resistant volume overload, oliguria, anuria, uremic complications and some drug intoxications.
The use of RRT in Intensive Care Unit (ICU) patients increased over the last decades. In ICU setting continuous renal replacement therapies (CRRT) like continuous veno-venous hemodialysis (CVVHD) and continuous veno-venous hemodiafiltration are frequently used. Especially haemodynamic unstable patients benefit from CRRT compared to intermittent hemodialysis. Exact timing of starting CRRT and optimal intensity is still unk-nown.
The ADVOS device is a newly developed dialysis system based on the use of recycled albumin dialysate. The system has shown a high detoxification capacity in in-vitro and preclinical studies. The ADVOS procedure com-bines various therapeutic features that might be beneficial for patients with AKI. The ADVOS® device is capab-le to correct acid-base disorders like metabolic acidosis. Recent studies demonstrated a strong potential of correction of acidosis in critically ill patients suffering from multiorgan failure. Although the device is approved, there is a lack of clinical studies comparing of its effect on acidosis versus to other dialysis devices, that all can be used during clinical routine according to its indication.
- Conditions
- Metabolic Acidosis
- Being tested
- ADVOS, CVVHD
- Keywords
- acidosis, dialysis, acute kidney injury, renal replacement therapy, intensive care medicine, ADVOS
- Medical subject headings
- Acidosis, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADVOSDevice
Also called ADVOS® device; ADVITOS
Modulation of acid-base regulation in patients with acute kidney injury, meta- bolic or mixed acidosis and indication for renal replacement therapy
CVVHDDevice
Also called multiFiltrate / multiFiltratePRO
Modulation of acid-base regulation in patients with acute kidney injury, meta- bolic or mixed acidosis and indication for renal replacement therapy
| Study group | Role | What they receive |
|---|---|---|
| ADVOS | Experimental | Application of the ADVOS device for Receives: Device: ADVOS |
| CVVHD | Active comparator | Application of CVVHD Receives: Device: CVVHD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hours alive with normal pH (≥ 7.35) within first 24 hours of therapy
pH values are measured to determine acidaemia in critically ill patients. As defined by the study protocol, pH ≤ 7.25 and base excess ≤ -6 mmol/l are required to diagnose metabolic or mixed acidosis. Normalisation of pH (defined as ≥ 7.35, representing the lower margin of the pyhsiological pH range) is used as a surrogate marker for reversal of acedaemia and, thereby, device effectiveness. The time (hours) alive within the defined physiological range after initiation of therapy in the first 24 hours will be used to compare the intervention and control group.
Measured: First 24 hours after initiation of study-specific therapy
Secondary outcomes (11)
Time to first pH normalisation (≥ 7.35)
pH values are measured to determine azidemia in critically ill patients. As defined by the study protocol, pH ≤ 7.25 and base excess ≤ -6 mmol/l are required to diagnose metabolic or mixed acidosis. Normalisation of pH (defined as ≥ 7.35, representing the lower margin of the pyhsiological pH range) is used as a surragate marker for reversal of acedaemia and, thereby, device effectiveness. The time (hours) until reaching the defined physiological range for the first time will be used to compare the intervention and control group.
Measured: First 24 hours after initiation of study-specific therapy
Days free of mechanical ventilation within the first 28d after randomization
Days free of mechanical ventilation across 28 days is used to compare the respiratory outcome between intervention and control group.
Measured: From start of study-specific therapy until day 28
Days free of vasopressor therapy within the first 28d after randomization
Days free of vasopressor therapy within the first 28 days after randomization are used as surrogate marker to compare sepsis/vasoplegia reversal between intervention and control group.
Measured: From initiation of study-specific therapy until day 28
Days free of renal replacement therapy within the first 28d after randomization
Days free of renal replacement therapy within the first 28 days after randomization are used as an indicator of renal organ failure. Need for and length of renal replacement therapy is a prognostic factor in critically ill intensive care patients.
Measured: Assessment at baseline, days 1, 2, 3, 7, 14, 21, 28 as long as patient is still on intensive care unit
Course of severity of organ failure
Severity of organ failures will be assessed on a daily basis using the Sequential Organ Failure Assessment (SOFA)-Score. Possible scores range from 0 to 24 points, whereby a higher score indicates a higher degree of organ failure.
Measured: Assessment at baseline, days 1, 2, 3, 7, 14, 21, 28 as long as patient is still on intensive care unit
Course of arterial blood gases
The dynamics of arterial blood gases will be used to compare the intervention and control group.
Measured: Time points Baseline, 0.5, 1, 2, 4, 6, 8, 12, 16, 20, 24, 48, 72 hours. If patient is still on intensive care unit, also on day 7, 14, 28
Course of systemic hemodynamics
The course of systemic haemodynamics is determined on the basis of vital parameters (e.g. mean arterial blood pressure, heart rate) as well as volume administration and catecholamine therapy will be used to compare the intervention and control group.
Measured: Timepoints Baseline, 0.5, 1, 2, 4, 6, 8, 12, 16, 20, 24, 48, 72 hours. If patient is still on intensive care unit, also on day 7, 14, 28
Intensive Care Unit and hospital length of stay
Time point for discharge from intensive care unit and hospital stay
Measured: Assessment of status on day 28 and day 90
28 days and 90 days mortality
Comparison of 28- as well as 90-day mortality between the study arms
Measured: Assessment of status on day 28 and day 90
Requirement and number of transfusions during ICU
The number of transfusions during ICU stay as well as the reason for need.
Measured: Cumulative assessment until day 28 or end of intensive care unit stay, whichever comes first.
Biomarkers (i.e. markers of inflammation, coagulation, endothelial function, metabolism, drug monitoring)
Analysis of the changes in different biomarkers during the study-specific therapy to compare the two study groups up to day 28 or the transfer of metabolism, drug monitoring)
Measured: Assessment at Baseline and time points 4, 16, 24, 48, 72 hours after initiation of study specific therapy as well as on day 7 and 28, if patient is still on intensive care unit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2023
- Study start17 Apr 2023
- Primary completion1 Apr 2024 (estimated)
- Study completion1 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic AcidosisStudies of the same condition, open and under way.
- More trials run by Universitätsklinikum Hamburg-EppendorfThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitätsklinikum Hamburg-Eppendorf
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olaf Boenisch, Principal investigator, Universitätsklinikum Hamburg-Eppendorf
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05842369
- Sponsor's protocol ID
- ADVOS-Acidosis UKE
- Status last verified
- May 2023
- First submitted
- 2 Apr 2023
- Last updated
- 9 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Two Approved Dialysis Methods for Treatment of Metabolic or Mixed Acidosis in Critically Ill Patients With Acute Kidney Injury and Indication for Renal Replacement Therapy
- ClinicalTrials.gov ID
- NCT05842369
- Acronym / sponsor ID
- ADVOS-Acidosis UKE
- Conditions
- Metabolic Acidosis
- Keywords
- acidosis, dialysis, acute kidney injury, renal replacement therapy, intensive care medicine, ADVOS
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Universitätsklinikum Hamburg-EppendorfUniversity, hospital or other
- Study start
- 17 Apr 2023 (actual)
- Primary completion
- 1 Apr 2024 (estimated)
- Study completion
- 1 Jul 2024 (estimated)
- First posted
- 6 May 2023 (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 aim of the study is to investigate the effects of ADVOS® therapy in critically ill patients with acute kidney injury, necessity of renal replacement therapy and acidosis.
The investigators aim at assessing superiority of ADVOS® versus CVVHD for the primary outcome hours alive with normal pH (arterial pH ≤ 7,35) until 24 hours in a modified intention-to-treat analysis (mITT: replacement if dropped out before treatment start).
Detailed description
Acute kidney injury (AKI) is frequently seen in patients treated at intensive care unit (ICU) and is associated with high morbidity and mortality. AKI occurs in more than 30% of critically ill patients. Various definitions for AKI have been used in the last decades, as a consequence reported incidence rates vary considerably from 13 to 78% in critically ill patients. AKI reflects a broad spectrum of clinical presentations, ranging from mild to se-vere injury, which may result in permanent loss of renal function. AKI is generally detected by a decrease in urine output (oliguria, anuria) and by an increase of renal serum markers (creatinine, blood-urea-nitrogen) with subsequent disorders in electrolyte homeostasis (e.g. hyperkalemia) and acid-base-regulation by means of metabolic acidosis. The AKIN criteria are well established criteria for diagnosis of AKI.
Different factors have been associated with development of AKI in critically ill patients. Age and pre-existing comorbidities are risk factors for development of AKI. Furthermore, infection and sepsis seem to be a mayor trigger for AKI. More than 50% of patients with septic shock develop AKI. Besides this radiocontrast agents, rapid progressive glomerulonephritis, rhabdomyolysis, trauma, circulatory shock, cardiac surgery, major non-cardiac surgery, nephrotoxic drugs and other causes are capable inducing AKI.
Metabolic acidosis, a frequent finding in AKI, is diagnosed when serum pH is reduced (pH < 7,35) and serum bicarbonate levels are abnormally low. Three major mechanisms lead to metabolic acidosis: 1) increased acid generation 2) loss of bicarbonate 3) decreased renal acid excretion. In AKI reduction of urine output and dimi-nished renal acid excretion results in subsequent metabolic acidosis.
Typical indications for renal replacement therapy (RRT) are hyperkalaemia, severe metabolic acidosis, diuretic-resistant volume overload, oliguria, anuria, uremic complications and some drug intoxications.
The use of RRT in Intensive Care Unit (ICU) patients increased over the last decades. In ICU setting continuous renal replacement therapies (CRRT) like continuous veno-venous hemodialysis (CVVHD) and continuous veno-venous hemodiafiltration are frequently used. Especially haemodynamic unstable patients benefit from CRRT compared to intermittent hemodialysis. Exact timing of starting CRRT and optimal intensity is still unk-nown.
The ADVOS device is a newly developed dialysis system based on the use of recycled albumin dialysate. The system has shown a high detoxification capacity in in-vitro and preclinical studies. The ADVOS procedure com-bines various therapeutic features that might be beneficial for patients with AKI. The ADVOS® device is capab-le to correct acid-base disorders like metabolic acidosis. Recent studies demonstrated a strong potential of correction of acidosis in critically ill patients suffering from multiorgan failure. Although the device is approved, there is a lack of clinical studies comparing of its effect on acidosis versus to other dialysis devices, that all can be used during clinical routine according to its indication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ADVOS | Experimental | Device: ADVOSApplication of the ADVOS device for |
| CVVHD | Active comparator | Device: CVVHDApplication of CVVHD |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Metabolic or mixed acidosis with pH ≤ 7.25 and base excess ≤ -6 mmol/l
- Age ≥ 18 years
- Acute kidney injury with need for Renal Replacement Therapy (RRT)
Key exclusion criteria (5 listed)
- Pregnancy
- Wards of the state/Prisoners
- Expected survival of less than 24 hours
- Contraindication for citrate anticoagulation
- Extracorporeal membrane oxygenation (ECMO)
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 |
|---|---|---|
| ADVOSAlso: ADVOS® device; ADVITOSModulation of acid-base regulation in patients with acute kidney injury, meta- bolic or mixed acidosis and indication for renal replacement therapy | Device | ADVOS |
| CVVHDAlso: multiFiltrate / multiFiltratePROModulation of acid-base regulation in patients with acute kidney injury, meta- bolic or mixed acidosis and indication for renal replacement therapy | Device | CVVHD |
Primary outcome
Hours alive with normal pH (≥ 7.35) within first 24 hours of therapy
Time frame: First 24 hours after initiation of study-specific therapy
pH values are measured to determine acidaemia in critically ill patients. As defined by the study protocol, pH ≤ 7.25 and base excess ≤ -6 mmol/l are required to diagnose metabolic or mixed acidosis. Normalisation of pH (defined as ≥ 7.35, representing the lower margin of the pyhsiological pH range) is used as a surrogate marker for reversal of acedaemia and, thereby, device effectiveness. The time (hours) alive within the defined physiological range after initiation of therapy in the first 24 hours will be used to compare the intervention and control group.
11 secondary outcomes
Time to first pH normalisation (≥ 7.35)
Time frame: First 24 hours after initiation of study-specific therapy
Days free of mechanical ventilation within the first 28d after randomization
Time frame: From start of study-specific therapy until day 28
Days free of vasopressor therapy within the first 28d after randomization
Time frame: From initiation of study-specific therapy until day 28
Days free of renal replacement therapy within the first 28d after randomization
Time frame: Assessment at baseline, days 1, 2, 3, 7, 14, 21, 28 as long as patient is still on intensive care unit
Course of severity of organ failure
Time frame: Assessment at baseline, days 1, 2, 3, 7, 14, 21, 28 as long as patient is still on intensive care unit
Course of arterial blood gases
Time frame: Time points Baseline, 0.5, 1, 2, 4, 6, 8, 12, 16, 20, 24, 48, 72 hours. If patient is still on intensive care unit, also on day 7, 14, 28
Course of systemic hemodynamics
Time frame: Timepoints Baseline, 0.5, 1, 2, 4, 6, 8, 12, 16, 20, 24, 48, 72 hours. If patient is still on intensive care unit, also on day 7, 14, 28
Intensive Care Unit and hospital length of stay
Time frame: Assessment of status on day 28 and day 90
28 days and 90 days mortality
Time frame: Assessment of status on day 28 and day 90
Requirement and number of transfusions during ICU
Time frame: Cumulative assessment until day 28 or end of intensive care unit stay, whichever comes first.
Biomarkers (i.e. markers of inflammation, coagulation, endothelial function, metabolism, drug monitoring)
Time frame: Assessment at Baseline and time points 4, 16, 24, 48, 72 hours after initiation of study specific therapy as well as on day 7 and 28, if patient is still on intensive care unit
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2023.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Olaf Boenisch principal investigator
Universitätsklinikum Hamburg-Eppendorf
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ADVOS and CVVHD in people with Metabolic Acidosis, run by Universitätsklinikum Hamburg-Eppendorf 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 3 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 9 May 2023. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Olaf Boenisch, MD (+4940741035315, o.boenisch@uke.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hours alive with normal pH (≥ 7.35) within first 24 hours of therapy (time frame: First 24 hours after initiation of study-specific therapy). 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 9 May 2023.