Intermittent ADVOS vs. Hemodialysis in Non-intensive Care Patients With Liver Dysfunction

Liver Cirrhosis Clinical Trial

— ADVOMITTENT  

Official title:

Prospective Randomized Controlled Trial for Protein-bound Toxins Removal With Intermittent ADVOS vs. Hemodialysis Treatment in Non-intensive Care Patients With Pre-existing Liver Dysfunction and Indication for Extracorporeal Renal Support. The ADVOMITTENT Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06129617
• Other study ID #: ADVOMITTENT
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2023
• Est. completion date: June 1, 2026

Study information

• Verified date: November 2023
• Source: University Medical Center Mainz
• Contact: Julia Weinmann-Menke, Prof.
• Phone: 0049 06131 17 2213
• Email: julia.weinmann-menke[@]unimedizin-mainz.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In the planned randomized controlled prospective pilot study, we aim to evaluate ADVOS compared with conventional hemodialysis regarding the elimination of protein-bound toxins in patients with therapy-refractory hepatorenal syndrome.

The study will be performed in a regular non-ICU ward with a large experience in the use of the ADVOS therapy.

Description:

Acute on chronic liver failure (ACLF) is a syndrome in patients with liver cirrhosis characterized by acute hepatic decompensation (i.e., jaundice, ascites, hepatic encephalopathy, bacterial infection, or gastrointestinal bleeding) and single or multi-organ failure, resulting in increased mortality. The European Association for the Study of the Liver (EASL) has established the Chronic Liver Failure (CLIF) consortium, which has developed a score for risk stratification and prognosis estimation, the CLIF-C ACLF score. Based on the CANONIC study, the CLIF consortium has developed a simplified CLIF Consortium Organ Failure Score (CLIF-C OFs), which includes liver, kidney, and lung function, hepatic encephalopathy, coagulation, and hemodynamics. Considering two other mortality factors (age and leukocyte count), the CLIF-C ACLF score was defined. The score has a higher predictive value for 28- and 90-day mortality than the Model of End Stage Liver Disease (MELD), MELD-Na, or Child-Turcotte-Pugh score.

Therapeutic options are limited and aim to address specific organ complications. In most cases, due to progressive renal insufficiency as part of hepatorenal syndrome, renal replacement therapy is if indicated. The only potential cure is liver transplantation.

There is some evidence that extracorporeal liver support can help a patient until liver transplantation or restoration of organ function. The Advanced Organ Support (ADVOS) system (ADVITOS GmbH, Munich, Germany) is an albumin-based advanced hemodialysis procedure, which can support the liver. The principles of conventional renal replacement therapy for the elimination of water-soluble substances are combined with the elimination of protein-bound substances by recirculating a dialysate containing 200 ml of human albumin. This procedure is typically used as continuous treatment in an intensive care setting. However, the investigators have already investigated the possibility of ADVOS as an intermittent procedure in patients with ACLF on a regular ward in a retrospective study.

To the best of knowledge of the investigators, there are currently no randomized studies comparing the elimination of protein-bound toxins between ADVOS and hemodialysis. Nevertheless, based on the investigators clinical experience, the investigators hypothesize that treatment with ADVOS may confer advantages over hemodialysis. Therefore, the objective of this study is to assess the effectiveness of ADVOS in comparison to hemodialysis for the treatment of patients with therapy-refractory hepatorenal syndrome.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 14
• Est. completion date: June 1, 2026
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Capacity of the patient to give consent

• Pre-existing liver disease in the sense of an ACLF with HRS

• Age >18 years

• Patient of the University Medical Center Mainz

• Bilirubin level = 4 mg/dl

• Indication for renal replacement procedure is based on STARRT-AKI criteria (serum potassium = 6 mmol/l in two independent blood samples; serum pH of 7.2 or less or serum bicarbonate of 12 mmol/l or less; respiratory failure secondary to volume excess)

Exclusion Criteria:

• Age < 18 years

• Pregnancy

• Contraindications for ADVOS therapy

• Already started renal replacement therapy

• Contraindication for citrate anticoagulation

• Use of vasopressors and MAD = 50 mmHg.

• Terminal cancer

Related Conditions & MeSH terms

• Acute Kidney Injury
• Kidney Failure, Acute
• Kidney Replacement
• Liver Cirrhosis
• Liver Diseases
• Multi Organ Failure
• Multiple Organ Failure
• Renal Insufficiency

Intervention

Device:
• Hemodialysis
5 treatments with hemodialysis on day 1, 2, 3, 5 and 7
• ADVOS
5 treatments with ADVOS on day 1, 2, 3, 5 and 7

Locations

Country	Name	City	State
Germany	UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz I. Medizinische Klinik und Poliklinik	Mainz	Rheinland-Pfalz

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Mainz	ADVITOS GmbH München

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	course of total bilirubin in patients blood	measurement of concentration of total bilirubin in serum of patients in mg/dl	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	course of uremia toxins in patients blood	measurement of blood urea nitrogen in serum of patients in mg/dl	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	course of bile acids	measurement of bile acids in serum of patients in mg/dl	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	evaluation of safety of ADVOS versus hemodialysis	Rate of complications during procedure (for example hypotension, electrolyte disorders etc.)	during the five interventions
Secondary	Quality of life raised in a standardized questionnaire	We will use the WHOQOL-BREF-questionnaire with 26 questions and values from 1 to 5; 1 being the lowes value and 5 the highest value	baseline before intervention and on days 28, 90, 180
Secondary	number of days in hospital during the intervention	we will measure the number of days in the hospital during the intervention from admission to our department until discharge from our department	admission in our department till discharge from our deparment
Secondary	course of pO2	we will measure the pO2 (in mmHg) in a blood sample with blood gas system (ABL800 FLEX Plus)	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	course of pCO2	we will measure the pCO2 (in mmHg) in a blood sample with blood gas system (ABL800 FLEX Plus)	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	course of base excess	we will measure the base excess (mmol/l) in a blood sample with blood gas system (ABL800 FLEX Plus)	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	course of pH	we will measure the pH in a blood sample with blood gas system (ABL800 FLEX Plus)	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	course of standard bicarbonat concentration	we will measure the standard bicarbonat concentration (mmol/l) in a blood sample with blood gas system (ABL800 FLEX Plus)	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	course of potassium	we will measure the potassium (mmol/l) in a blood sample with blood gas system (ABL800 FLEX Plus)	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	course of sodium	we will measure the sodium (mmol/l) in a blood sample with blood gas system (ABL800 FLEX Plus)	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	course of ionised calcium	we will measure the ionised calcium (mmol/l) in a blood sample with blood gas system (ABL800 FLEX Plus)	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	course of bilirubin	we will measure the bilirubin (in mg/dl) in a blood sample	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	course of INR	we will measure the INR in a blood sample	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	course of albumin	we will measure the albumin (in g/l) in a blood sample	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	course of kidney function	we will measure the kreatinine (in mg/dl) in a blood sample	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	course of MELD	MELD = Model for End-stage Liver Disease (6-40, Higher numbers indicate increased mortality)	Within 6 hours before first treatment and within 2 hours after 5 treatments
Secondary	course of CLIF-C ACLF score	CLIF-C ACLF Score = Chronich Liver failure Consortium acute on chronic liver failure score (6-15, higher numbers indicate increased mortality)	Within 6 hours before first treatment and within 2 hours after 5 treatments
Secondary	course of hepatic encephalopathy	an experienced clinician will determine the grade of the hepatic encephalopathy using the west haven criteria (grade 1 till grade 4, "grade 1" beeing the lowest value und "grade 4" beeing the highest value)	Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary	mortality		28, 90 and 180 days.
Secondary	elimination of blood urea nitrogen	We will measure the Blood urea nitrogen (mg/dl) in a blood sample	Within 6 hours before first treatment and within 2 hours after every treatment session