An interventional study of Coupled plasma filtration and adsorption (CPFA) in Liver Failure, Acute and Liver Failure, Acute on Chronic, sponsored by IRCCS Azienda Ospedaliero-Universitaria di Bologna. Completed at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-03-17.
Sponsored by IRCCS Azienda Ospedaliero-Universitaria di Bologna · Not applicable, Interventional, and Supportive care
Among 10 studies in Acute-On-Chronic Liver Failure with a site in Italy — 5 open to participants now, 5 under way, none of them phase 3. Acute-On-Chronic Liver Failure · Italy.
Among the 10 studies in Acute-On-Chronic Liver Failure with a site in Italy, this one is the only one that started in 2013, is the only one with no phase, and was the 1st registered.
165 studies on the registry are indexed under Acute-On-Chronic Liver Failure; 60 are open to participants now.
This study's enrollment of 12 is below the median of 72 across 95 interventional studies indexed under Acute-On-Chronic Liver Failure.
Browse Acute-On-Chronic Liver Failure studies →5 of the 10 studies in Acute-On-Chronic Liver Failure with a site in Italy are open now, in 12 countries. Each count lists the studies.
Of the 32 Acute-On-Chronic Liver Failure studies recruiting now, 11 (34%) set no upper age limit and 15 (47%) stop at 75 or younger; 3 take children under 18; 2 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →10 studies; the count open now beside each. This study's row is marked.
First in 2013; this study’s year is marked. 1 started in 2013.
Median enrollment 90 across the 5 interventional studies, 400 across the 5 observational. Of the 5 that completed or were terminated, 2 (40%) have results posted.
4 of 10 have an industry lead sponsor. The 7 most frequent:
IRCCS Azienda Ospedaliero-Universitaria di Bologna is the lead sponsor of 511 studies on the registry; 287 are open to participants now.
IRCCS Azienda Ospedaliero-Universitaria di Bologna has 2 studies filed under Acute-On-Chronic Liver Failure — fewer than ten, so there is no comparison to draw.
1 of the studies in Acute-On-Chronic Liver Failure with a site in Italy that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT04613921European Foundation for Study of Chronic Liver FailureLiver Transplantation in Patients With CirrHosis and Severe Acute-on-Chronic Liver Failure: iNdications and outComEs | 2026-12-31 |
Among the 10 studies in Acute-On-Chronic Liver Failure with a site in Italy, from their registry updates:
Nothing recorded among them since 2026-09-25.
CPFA is currently used in the treatment of severe sepsis with the intention of removing the proinflammatory mediators from the systemic circulation. Some evidence exists about the bilirubin adsorbing ability of the neutral styrenic resin which is part of the extracorporeal circuit of CPFA. The aim of this study is to assess efficacy and safety of CPFA in extracorporeal detoxification of liver toxins in patients affected by acute or acute-on-chronic liver failure.
CPFA allows an improvement of blood pressure and inflammatory response during sepsis and multiorgan failure. This extracorporeal detoxification system was developed to non-specifically remove larger mediators during systemic inflammation with an extracorporeal circuit consisting of a plasma filter, a resin cartridge and a high-flux dialyzer. At present it is performed with the use of a five-pump modular treatment consisting of a plasma filter and a following absorption on an unselective hydrophobic resin cartridge and a final passage of the reconstituted blood through a high permeability polyethersulfone haemofilter, in which convective exchanges may be applied in a postdilution mode. Ronco et al. in 2002 compared CPFA treatment to continuous veno-venous haemodiafiltration (CVVHDF) in 10 patients affected by septic shock. The patients underwent 10-hour length CPFA and an increase of arterial blood pressure and a significant reduction of norepinephrine dosage were observed in comparison to the arterial blood pressure and the norepinephrine dosage achieved with the CVVHDF treatment. Formica et al. in 2004 confirmed these results using 100 CPFA treatments in 12 patients affected by septic shock with or without acute kidney injury. Patient survival at 28 days was 90%, while survival of after 90 days was 70%. Mao et al. also compared CPFA with High Volume Hemofiltration and they showed that CPFA increased the ratio between anti-inflammatory and pro-inflammatory cytokines; CPFA enhanced Human Leucocyte Antigen (HLA) class II expression on monocytes and improved the leukocyte response to inflammation measuring leukocyte production of Tumor Necrosis Factor-alfa. Recently Livigni et al. on behalf of the Italian group for the evaluation of interventions in intensive care medicine carried out a randomised controlled trial enrolled 330 adult patients with septic shock, 192 were randomised to either have CPFA added to the standard care, or not. CPFA was to be performed daily for 5 days, lasting at least 10 h/day. The trial was stopped because nearly 50% of the patients could not achieve treatment completion due to technical reasons (primarily coagulation). The trial did observe that patients with the highest amounts of treated plasma appeared to have a survival benefit. The technique underwent further modifications to improve the technical aspects and anticoagulation and a new trial is now underway with a high dose of plasma > 0.18 litres/ kg/ day.
As to the hepatic toxin removal it depends on the ability of the detoxification system to extract albumin bound toxins by means of adsorption. The adsorption consists in the consolidation on the surface of a solid material of molecules floating in a fluid after matching the fluid with the solid. The consolidation is due to weak bounds as in the case of Van der Waals and hydrophobic bounds. The selectivity of adsorption occurs when albumin molecules easily pass throughout the sorbent while the sorbent draw the albumin carried toxins into the pores of the sorbent. The hepatic toxins often are hydrophobic and with molecular weight \< 1,000 daltons (bilirubin = 406 daltons, cholic acid = 283 daltons, chenodeoxycholic acid = 272 daltons). The albumin structure consists in 3 domains, which allows a multi-binding protein transport. As to bilirubin, its protein binding is a physiological protective mechanism to prevent the free bilirubin diffusion and toxicity in human tissues. The amount of bilirubin production is about 300 gr/day. The molecule most tightly bound to albumin is non-conjugated bilirubin: the amount of non-conjugated bilirubin not bound to albumin is \< 0.1%. Non-conjugated bilirubin is currently considered as "indirect" bilirubin because it gives an indirect reaction with standard diazo reagents. Conjugated bilirubin is also bound to albumin but with a reduced affinity. The albumin-bilirubin bond occurs by means of covalent or non-covalent strengths. The 2 bilirubin binding sites on albumin show different constant of association (Ka). The primary site has a high affinity, its Ka is 55-68 micromol/L and it can bind only 1 mole of bilirubin. The secondary site has a low affinity, its Ka is 4.4-5.0 micromol/L and it can bind more than 1 mole of bilirubin. A gap between 20 and 50 ångström between albumin and the sorbent is needed to move bilirubin from albumin to the sorbent.
The CPFA efficacy on bilirubin adsorption is based on hydrophobic polystyrene-divinylbenzene copolymer matrices of the resin cartridge that have mean pore sizes of 30 nanometres. Harm et al. reported that the hydrophobic polystyrene-divinylbenzene copolymer of CPFA resin cartridge (type B copolymer: mean diameter 128 micron, pore size 30 nanometres and surface area of 700 m2/gr of resin) binds higher amount of bilirubin than the amount of bilirubin bound with the other kinds of polystyrene-divinylbenzene copolymer matrices tested (type A copolymer: mean diameter 120 micron, pore size 15 nanometres and surface area of 900 m2/gr of resin; type C copolymer: mean diameter 37 micron, pore size 100 nanometres and surface area of 200 m2/gr of resin).
Few authors in vivo assessed the bilirubin adsorbing ability of the neutral styrenic resin of CPFA. Caroleo et al. reported the first case of hepatic toxins removal by means of CPFA in a patient affected by acute liver failure due to cardiogenic shock. Maggi et al. reported 2 further cases where bilirubin removal was obtained in 2 patients with delayed graft function after liver transplantation. The patients achieved a 40% bilirubin reduction after 3 treatments with CPFA lasting 3-hours each.
165 studies on the registry are indexed under Acute-On-Chronic Liver Failure; 60 are open to participants now.
This study's enrollment of 12 is below the median of 72 across 95 interventional studies indexed under Acute-On-Chronic Liver Failure.
Browse Acute-On-Chronic Liver Failure studies →IRCCS Azienda Ospedaliero-Universitaria di Bologna is the lead sponsor of 511 studies on the registry; 287 are open to participants now.
Compared within Acute-On-Chronic Liver Failure, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Liver Failure, Acute. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Patients affected by acute or acute on chronic liver failure who undergo Coupled plasma filtration and adsorption (CPFA) to recover their basal liver function or as a bridge to liver transplantation. The intervention is CPFA treatment which lasts 6 hour length. The intervention can be repeated for a maximum of 5 times.
Device: Coupled plasma filtration and adsorption (CPFA)
Patients affected by acute or acute on chronic liver failure are enrolled to undergo CPFA extracorporeal treatments and the standard medical therapy to recover their basal liver function or as a "bridge" to liver transplantation
The mortality reduction of patients with acute or acute on chronic liver failure;
The measure is the overall survival of the patients after CPFA and standard medical therapy
Time frame: 1 year
Efficacy of liver toxins detoxification
The measures of efficacy consist in the evaluation bilirubin levels, biliary acids levels, ammonia levels and lactate levels
Time frame: 1 year.
Improvement of hepatic encephalopathy
The measure of hepatic encephalopathy is assessed by means of the West Haven Criteria
Time frame: 1 year
Improvement of the arterial blood pressure of the patients
Measuring arterial blood pressure (mmHg) on starting CPFA, during the CPFA treatment and at CPFA end.
Time frame: 1 year
Biocompatibility of CPFA
Blood leukocytes, platelets, Hemoglobin are assessed before and after each CPFA treatment
Time frame: 1 year
Cytokines clearance during CPFA
Interleukin-6, Tumor Necrosis Factor alfa, Interleukin-10, Hepatocyte growth factor are assessed before and after each CPFA treatment
Time frame: 1 year
Plan to share: No
Ran from Jun 2013 to primary completion in Dec 2018, 66 months.
Of 32 interventional studies with no phase under Acute-On-Chronic Liver Failure, half reached primary completion within 29 months of starting (the median), counting those still running; a quarter within 23 and three quarters within 50. This study's 66 months is above that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2021. You cannot join it, but the record below documents what was studied.
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Acute-On-Chronic Liver Failure →
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