Clinical trial NCT06129617: Intermittent ADVOS vs. Hemodialysis in Non-intensive Care Patients With Liver Dysfunction
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Liver Cirrhosis
Kidney Failure, Acute
Kidney Replacement
Multi Organ Failure
Lead sponsor: University Medical Center Mainz
Sponsor class: OTHER
Collaborators: name: ADVITOS GmbH München
First posted: 2023-11-13
Enrollment: 14
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: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: course of total bilirubin in patients blood
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
Secondary outcomes:
measure: course of uremia toxins in patients blood
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: course of bile acids
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: evaluation of safety of ADVOS versus hemodialysis
timeFrame: during the five interventions
measure: Quality of life raised in a standardized questionnaire
timeFrame: baseline before intervention and on days 28, 90, 180
measure: number of days in hospital during the intervention
timeFrame: admission in our department till discharge from our deparment
measure: course of pO2
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: course of pCO2
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: course of base excess
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: course of pH
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: course of standard bicarbonat concentration
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: course of potassium
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: course of sodium
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: course of ionised calcium
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: course of bilirubin
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: course of INR
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: course of albumin
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: course of kidney function
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: course of MELD
timeFrame: Within 6 hours before first treatment and within 2 hours after 5 treatments
measure: course of CLIF-C ACLF score
timeFrame: Within 6 hours before first treatment and within 2 hours after 5 treatments
measure: course of hepatic encephalopathy
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
measure: mortality
timeFrame: 28, 90 and 180 days.
measure: elimination of blood urea nitrogen
timeFrame: Within 6 hours before first treatment and within 2 hours after every treatment session
Other outcomes:
Locations:
city: Mainz
country: Germany
facility: UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz I. Medizinische Klinik und Poliklinik
state: Rheinland-Pfalz
Study officials:
affiliation: Principal Investigator
name: Julia Weinmann-Menke, Prof.
role: PRINCIPAL_INVESTIGATOR
References: