Clinical trial NCT05842369: ADVOS® Versus CVVHD in Metabolic or Mixed Acidosis
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Metabolic Acidosis
Keywords: acidosis
dialysis
acute kidney injury
renal replacement therapy
intensive care medicine
ADVOS
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
First posted: 2023-05-06
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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) 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.

Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

* Pregnancy
* Wards of the state/Prisoners
* Expected survival of less than 24 hours
* Contraindication for citrate anticoagulation
* Extracorporeal membrane oxygenation (ECMO)

Primary outcomes:
measure: Hours alive with normal pH (≥ 7.35) within first 24 hours of therapy
timeFrame: First 24 hours after initiation of study-specific therapy
Secondary outcomes:
measure: Time to first pH normalisation (≥ 7.35)
timeFrame: First 24 hours after initiation of study-specific therapy
measure: Days free of mechanical ventilation within the first 28d after randomization
timeFrame: From start of study-specific therapy until day 28
measure: Days free of vasopressor therapy within the first 28d after randomization
timeFrame: From initiation of study-specific therapy until day 28
measure: Days free of renal replacement therapy within the first 28d after randomization
timeFrame: Assessment at baseline, days 1, 2, 3, 7, 14, 21, 28 as long as patient is still on intensive care unit
measure: Course of severity of organ failure
timeFrame: Assessment at baseline, days 1, 2, 3, 7, 14, 21, 28 as long as patient is still on intensive care unit
measure: Course of arterial blood gases
timeFrame: 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
measure: Course of systemic hemodynamics
timeFrame: 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
measure: Intensive Care Unit and hospital length of stay
timeFrame: Assessment of status on day 28 and day 90
measure: 28 days and 90 days mortality
timeFrame: Assessment of status on day 28 and day 90
measure: Requirement and number of transfusions during ICU
timeFrame: Cumulative assessment until day 28 or end of intensive care unit stay, whichever comes first.
measure: Biomarkers (i.e. markers of inflammation, coagulation, endothelial function, metabolism, drug monitoring)
timeFrame: 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
Other outcomes:
Locations:
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
Study officials:
affiliation: Universitätsklinikum Hamburg-Eppendorf
name: Olaf Boenisch
role: PRINCIPAL_INVESTIGATOR
References: