Plasma Exchange for Liver Failure
(APACHE Trial)
Recruiting in Palo Alto (17 mi)
+30 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: Grifols Therapeutics LLC
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This is a Phase 3, multicenter, randomized, controlled, parallel-group, open-label study to evaluate the effects of plasma exchange using human serum albumin 5% (PE-A 5%) in acute-on-chronic liver failure (ACLF) subjects. The study will involve approximately 40 study centers in the United States, Canada, and Europe with expertise in the management of subjects with ACLF.
Subjects with ACLF at a high risk of hospital mortality will be enrolled. The study will consist of a Screening Period during which subjects will be randomized (1:1) to receive either standard medical treatment (SMT) + PE-A 5% (treatment group) or SMT only (control group), followed by a Treatment Period, and a Follow-up Period.
The Treatment Period for subjects in the SMT+ PE-A 5% treatment group will be between 7 and 17 days, depending on ACLF evolution.
The Treatment Period for subjects in the SMT control group will be a minimum of 7 days for all subjects and up to 17 days depending on the ACLF evolution. Subjects in this group will receive SMT according to the institution's standards.
The Follow-up Period for subjects in both groups will be 90 days.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on anti-platelet or anti-coagulant therapy, except for LMWH for DVT prophylaxis.
What data supports the idea that Plasma Exchange for Liver Failure is an effective treatment?
The available research shows that Plasma Exchange (PE) is an effective treatment for liver failure. One study found that PE combined with another method called double plasma molecular adsorption system (DPMAS) was more effective than using PE alone, especially in the early stages of liver failure. This combination improved the treatment efficiency and reduced the need for plasma. Another study showed that PE helps lower harmful substances in the blood, like ammonia, which is important for patients with liver failure. Additionally, a meta-analysis of several studies found that combining PE with DPMAS improved survival rates and treatment effectiveness compared to using PE alone. These findings suggest that PE, especially when combined with other methods, is a beneficial treatment for liver failure.
12345What safety data is available for plasma exchange using human albumin solutions?
Several studies have evaluated the safety of human albumin solutions used in plasma exchange. A study on Albumex 5 found a low adverse event rate, with no serious events reported. Another study compared two albumin solutions and found no significant difference in overall safety, though preparation methods affected the type of adverse reactions. A large survey of Zenalb 4.5% solution reported a low incidence of adverse reactions, with no significant impact from plasma source or manufacturing method. Additionally, Albunex, an albumin-based ultrasound contrast agent, showed no immunogenic response in volunteers. Overall, human albumin solutions are generally well-tolerated in plasma exchange procedures.
678910Is the treatment PE-A 5% a promising treatment for liver failure?
Yes, PE-A 5% is a promising treatment for liver failure. Plasma exchange, which includes treatments like PE-A 5%, has been shown to help patients with liver failure by improving survival rates, reducing harmful substances in the blood, and supporting patients until they can receive a liver transplant.
123411Eligibility Criteria
This trial is for men and women aged 18-79 with cirrhosis experiencing acute-on-chronic liver failure (ACLF) grades 1b, 2, or 3a. Participants must be able to consent or have a representative who can. Exclusions include severe infections, respiratory failure, certain cancers, pregnancy, drug addiction (except alcohol/marijuana), recent participation in other trials, and various severe health conditions.Inclusion Criteria
Subjects with ACLF-1b, ACLF-2, or ACLF-3a detected either at admission or during hospitalization (must be ACLF-1b, -2, or -3a within the Screening Period [a maximum of 10 days])
If I'm unable to consent, a family member or legal representative will do so for me.
I am between 18 and 79 years old with liver cirrhosis.
+1 more
Exclusion Criteria
My liver failure condition improved or worsened during the screening period.
I have severe lung disease (GOLD stage III or IV).
I have had a liver transplant.
+21 more
Participant Groups
The study compares standard medical treatment (SMT) alone versus SMT combined with plasma exchange using human serum albumin 5% (PE-A 5%) in patients with ACLF. It's randomized and open-label; participants will receive treatments for up to 17 days based on their condition's progression followed by a three-month follow-up.
2Treatment groups
Experimental Treatment
Active Control
Group I: SMT+ PE-A 5%Experimental Treatment1 Intervention
PE-A 5% will be performed using 5% albumin (Albutein 5%) as the main replacement fluid administered intravenously.
Group II: Standard Medical Treatment (SMT)Active Control1 Intervention
Standard medical treatment (SMT) will be administered according to institution standards.
PE-A 5% is already approved in United States, Canada, European Union for the following indications:
🇺🇸 Approved in United States as Human Serum Albumin 5% for:
- Hypovolemia
- Hypoalbuminemia
- Acute-on-chronic liver failure
🇨🇦 Approved in Canada as Albumin (Human) 5% Solution for:
- Hypovolemia
- Hypoalbuminemia
- Acute-on-chronic liver failure
🇪🇺 Approved in European Union as Human Serum Albumin 5% for:
- Hypovolemia
- Hypoalbuminemia
- Acute-on-chronic liver failure
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Rutgers-New Jersey Medical SchoolNewark, NJ
Emory UniversityAtlanta, GA
Cedars-Sinai Medical CenterLos Angeles, CA
Aurora Health Care, Inc.Milwaukee, WI
More Trial Locations
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Who Is Running the Clinical Trial?
Grifols Therapeutics LLCLead Sponsor
Instituto Grifols, S.A.Industry Sponsor
References
Standard-Volume Plasma Exchange Improves Outcomes in Patients With Acute Liver Failure: A Randomized Controlled Trial. [2022]High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain.
[Comparison of curative effect of low flow rate plasma exchange combined with hemofiltration for treatment of liver failure]. [2009]To investigate the effect of plasma exchange (PE) combined with hemofiltration (HF) on liver failure.
[Plasma exchange combined with double plasma absorption therapy improve the prognosis of acute-on-chronic liver failure]. [2019]Objective: To compare the efficacy and safety of plasma exchange (PE) combined with double plasma absorption and simple PE in the treatment of acute-on-chronic liver failure. Methods: We retrospectively analyzed 251 cases of acute-on-chronic liver failure treated with artificial liver treatment since January 2015. Changes in clinical manifestations, laboratory tests, and complications of the patients before and after different modes of treatment were compared and short-term efficacy was tracked. In accordance with different data, t-test, Pearson's chi-squared test and Fisher's exact test were used for statistical analysis. Results: The effectiveness of low-volume PE combined with double plasma molecular adsorption system (DPMAS) and equal amount of PE combined with DPMAS was significantly better than simple PE (83.7%, 84.05% and 82.15 vs 55.6%, P < 0.05) in early stage of liver failure. In late-stage of liver failure, there was no significant difference in the treatment efficiency of each group (P > 0.05). Bilirubin and bile acid levels were significantly decreased in combined treatment groups than that to simple PE group (P < 0.05). PTA and albumin improvement rate of DPMAS PE groups were significantly lower than that of simple PE group (P < 0.05). There was no statistical difference in adverse reactions between each group. Conclusion: PE combined with DPMAS improves the treatment efficiency of early hepatic failure and decrease dosage of plasma when compared with simple PE. A beforehand DPMAS treatment after PE treatment can improve the adverse effects of DPMAS on blood coagulation function and albumin levels.
Changes of ammonia levels in patients with acute on chronic liver failure treated by plasma exchange. [2014]Acute on chronic liver failure (AoCLF) is associated with a high mortality rate. Plasma exchange (PE) is useful to bridge AoCLF patients to liver transplantation. The aim of this study was to assess the effects of PE on plasma ammonia levels (PAL) in AoCLF patients.
[Meta-analysis of the therapeutic value of plasma exchange simple or combined with dual plasma molecular adsorption system for liver failure]. [2023]Objective: To systematically analyze the serological parameters, effective rate and survival rate of patients with liver failure after simple plasma exchange treatment and half-dose plasma exchange combined with dual plasma molecular adsorption system. Methods: Randomized controlled trials published in the full-text articles of Pubmed, Embase, Web of Science, The Cochrane Library, Wanfang, Weipu, CNKI, and other journals from June 2020 were retrieved. Revman 5.3 software was used to conduct the meta-analysis after the literature quality evaluation. Results: A total of 10 studies involving 884 cases were selected. Among them, 425 and 459 were treated with combination and simple plasma exchange therapy. The levels of TBIL (MD=-28.58, 95% CI: -37.42～-19.75, P<0.000 01) and ALB (MD=-2.00, 95%CI:-2.61～-1.39, P<0.000 01) were lower in the combined treatment group than those in the simple treatment group, and the difference was statistically significant. HGB (MD=5.96, 95%CI: 1.52-10.40, P=0.009), effective rate (OR=1.92, 95%CI: 1.29-2.85, P=0.001), and survival rate (OR=1.63, 95%CI: 1.13-2.36, P=0.009) were higher in the combined treatment group than those in the simple treatment group, and the difference was statistically significant.The two treatment methods had good curative effects for the improvement of ALT, AST, DBIL, PTA, INR, and PLT levels (P＜0.05), and there was no statistically significant difference between them (P＞0.05). Conclusion: Half-dose plasma exchange combined with dual plasma molecular adsorption system therapy not only effectively improves hyperbilirubinemia, efficacy, and survival rate while significantly reducing plasma dosage, but it also has fewer adverse effects on hemoglobin depletion in patients with liver failure than simple plasma exchange therapy.
A safety study of Albumex 5, a human albumin solution produced by ion exchange chromatography. [2019]Human serum albumin solutions have been used as plasma replacement fluids for many years and adverse events associated with their use are rare. Albumex 5 is a new albumin solution manufactured by a combination of the Cohn fractionation process and a chromatographic technique. A multicentre, randomised study was conducted to compare the safety of Albumex 5 and 5% normal serum albumin (5% NSA) in patients undergoing large volume therapeutic plasmapheresis for a variety of disorders. Up to six exchanges were performed on each patient. A total of 208 evaluable exchanges were performed on 40 patients, 109 5% NSA and 99 Albumex 5. There were 9 adverse events (reaction rate of 8.3%) in 6 patients with 5% NSA and 12 events (reaction rate 12.1%) in 8 patients with Albumex 5. The difference is not statistically significant (p = 0.37, Fisher's exact test). None of the adverse events were considered serious. Only six reactions were thought to be possibly related to the product and three exchanges were modified as a result of an adverse event; one with Albumex 5 was interrupted and two with 5% NSA were slowed. Albumex 5 can be considered to be a safe product with a low adverse event rate.
[Side effects of therapeutic plasma exchange. A controlled prospective study]. [2016]Solutions of human albumin are generally used as plasma substitutes during therapeutic plasma exchanges. The safety of 2 solutions of human albumin was evaluated in a multicentre, randomized, double-blind trial. Between June, 1984 and February, 1986, 80 patients who were undergoing plasma exchanges for the first time entered the study and were randomly assigned into 2 groups according to whether they received plasma albumin (PM) or placental albumin (PC). Each patient had 6 plasma exchanges over a 2-week period. Failure was defined as the occurrence of an untoward effect during an exchange. No significant difference in the number of failures was found between the 2 albumins (PM 23/40, PC 15/40; P = 0.07). However, when the type of adverse reaction was taken into account there was a significant difference between the two treatment groups regarding the number of febrile episodes (PM 8, PC 2; P = 0.043) and shivering fits (PM 9, PC 2; P = 0.023). Thus, the nature of the albumin has no significant influence on the overall safety of plasma exchanges, but it seems that different methods of preparation may affect the type of untoward effect observed.
Experience of using human albumin solution 4.5% in 1195 therapeutic plasma exchange procedures. [2016]The aim of the study was to document the incidence of adverse reactions (ADRs) in subjects undergoing therapeutic plasma exchange with human albumin 4.5% solution (Zenalb 4.5) and to explore whether there were any differences in tolerability with a change from UK to US plasma and a subsequent manufacturing modification. Zenalb 4.5 was initially manufactured from recovered plasma from UK blood donations and later from source plasma from US donors. The modification was a salt diafiltration step. A prospective survey was conducted at three UK aphaeresis units; data from 154 subjects undergoing 1195 plasma exchanges using Zenalb 4.5 were collected. Adverse events with at least a possible relationship to treatment were recorded. There were 20 ADRs per 1195 exchanges (1.7%), experienced by 14 subjects (9.1%). The most common reaction was rigours in 17 exchanges (1.4%) and 12 subjects (7.8%). ADRs occurred in 0.8% (2/250) of plasma exchanges with UK plasma, 0.2% (1/539) using US plasma/original manufacturing method, 4.3% (16/370) using US plasma/modified method and 12.5% (1/8) using US plasma/mixed original and modified methods. Data were incomplete for the remaining 28 exchanges, but no ADRs were reported. Moreover, 17 ADRs occurred over a 14-month period and involved 10 batches manufactured from US plasma (1 original, 9 by modified method). The incidence then returned to the previously lower level. There was no explanation for this cluster of events. Overall, there was no evidence that plasma source or manufacturing method affected tolerability and it was concluded that human albumin 4.5% solution (Zenalb 4.5) is well tolerated during plasma exchange therapy.
Lack of an immune response to Albunex, a new ultrasound contrast agent based on air-filled albumin microspheres. [2018]Albunex is a new ultrasound contrast agent consisting of air-filled microspheres of heat-aggregated human albumin suspended in a 5% (w/v) solution of human albumin for infusion. The structural alterations induced in the albumin molecules during heat aggregation may cause the formation of new epitopes that may provoke an immunological response in recipients. To assess the possible immunogenicity of the contrast agent, 34 healthy volunteers were randomized to receive four injections of either Albunex or 5% human serum albumin (0.01 ml/kg) at 4-week intervals. Analysis of blood samples taken 3 weeks after each injection did not reveal any formation of IgE or IgG antibodies directed against the Albunex microsphere protein or albumin in any of the recipients. The evaluation of novel enzyme immunosorbent assays developed to detect the presence of these specific IgE and IgG antibodies is described. It was also investigated whether the heat-aggregated microsphere albumin was structurally altered in such a way that it could be recognized by cat albumin specific IgE, present in the sera of individuals allergic to cat albumin. 187 serum samples shown to contain elevated levels of cat albumin specific IgE were used in the study. No cross-reactive binding of the heat-aggregated human albumin to anticat albumin IgE could be detected. There is no evidence from the present studies that the heat-aggregated albumin of the Albunex microspheres will provoke an immunological reaction upon repeated injections or cause an adverse reaction when administered to allergic individuals having cat albumin as one of their allergens.
Therapeutic plasma exchange for the management of a type III hypersensitivity reaction and suspected immune-mediated vasculitis assumed to be caused by human albumin administration in a dog. [2022]To describe the successful treatment of a life-threatening type III hypersensitivity reaction suspected to have been related to human serum albumin (HSA) administration in a dog with therapeutic plasma exchange (TPE).
Blood purification for postoperative liver failure with special reference to chronic hepatic support for those awaiting liver transplantation. [2016]Blood purification, mainly plasma exchange (PE), was carried out for 13 cases of acute, and two cases of chronic postoperative liver failure. Four of thirteen acute cases (31%) survived. Although only one of eight with chronic liver disease survived, three of five without chronic liver disease survived. In most of those who lived, other organ failure occurred less often; total bilirubin and blood ammonia were less than 15 mg/dl and 200 micrograms/dl, respectively, before PE: and total bilirubin, blood ammonia, and branched chain amino acid/aromatic amino acid (BCAA/AAA) ratios recovered after five or fewer sessions of PE. Two chronic cases, treated for 1 and 4 years, respectively, were good candidates for liver or multiple organ transplantation. Although both died, PE was effective in reducing jaundice and in improving consciousness and general condition. Plasma exchange should be introduced early after assessing the changes in total bilirubin, blood ammonia, and coma grade in patients with acute postoperative liver failure. Plasma exchange could be useful as a chronic hepatic support system for those awaiting liver transplantation.